Carboplatin, a second-generation platinum chemotherapeutic drug, is considerably less ototoxic than cisplatin. While common laboratory species such as mice, guinea pigs and rats are highly resistant to carboplatin oto...Carboplatin, a second-generation platinum chemotherapeutic drug, is considerably less ototoxic than cisplatin. While common laboratory species such as mice, guinea pigs and rats are highly resistant to carboplatin ototoxicity, the chinchilla stands out as highly susceptible. Moreover, carboplatin causes an unusual gradient of cell death in chinchillas. Moderate doses selectively damage type I spiral ganglion neurons (SGN) and inner hair cells (IHC) and the lesion tends to be relatively uniform along the length of the cochlea. Higher doses eventually damage outer hair cells (OHC), but the lesion follows the traditional gradient in which damage is more severe in the base than the apex. While carboplatin ototoxicity has been well documented in adult animals in vivo, little is known about its in vitro toxicity. To elucidate the ototoxic effects of carboplatin in vitro, we prepared cochlear and vestibular organotypic cultures from postnatal day 3 rats and adult chinchillas. Chinchilla cochlear and vestibular cultures were treated with carboplatin concentrations ranging from 50 μM to 10 mM for 48 h. Consistent with in vivo data, carboplatin selectively damaged IHC at low concentrations (50-100 μM). Surprisingly, IHC loss decreased at higher doses and IHC were intact at doses exceeding 500 μM. The mechanisms underlying this nonlinear response are unclear but could be related to a decrease in carboplatin uptake via active transport mechanisms (e.g., copper). Unlike the cochlea, the carboplatin dose-response function increased with dose with the highest dose destroying all chinchilla vestibular hair cells. Cochlear hair cells and auditory nerve fibers in rat cochlear organotypic cultures were unaffected by carboplatin concentrations <10 μM; however, the damage in OHC were more severe than IHC once the dose reached 100 μM. A dose at 500 μM destroyed all the cochlear hair cells, but hair cell loss decreased at high concentrations and nearly all the cochlear hair cells were present at the highest dose, 5 mM. Unlike the nonlinear dose-response seen with cochlear hair cells, rat auditory nerve fiber and spiral ganglion losses increased with doses above 50 μM with the highest dose destroying virtually all SGN. The remarkable species differences seen in vitro suggest that chinchilla IHC and type I SGN posse some unique biological mechanism that makes them especially vulnerable to carboplatin toxicity.展开更多
BACKGROUND: Patients with carcinoma of the gallbladder have advanced, unresectable tumor at the time of presentation and face a dismal prognosis in the absence of a standard palliative chemotherapy regimen. This study...BACKGROUND: Patients with carcinoma of the gallbladder have advanced, unresectable tumor at the time of presentation and face a dismal prognosis in the absence of a standard palliative chemotherapy regimen. This study was undertaken to evaluate the efficacy and safety of combined chemotherapy of gemcitabine and carboplatin in 20 patients with advanced gallbladder carcinoma. METHODS: The criteria of eligibility included chemonaive patients with unresectable gallbladder cancer, bidimensionaIly measurable disease, Zubrod’s performance status≤2, and adequate major organ function. The patients received gemcitabine (1000 mg/m^2) on days 1 and 8, and carboplatin (target AUC of 5.0 mg/ml) on day 1, in a 21-day cycle. CT was used for response assessment. RESULTS: In this group of 20 patients with advanced gallbladder carcinoma 6 were men and 14 women, with a median age of 55 years. The stage of the tumor at presentation was IVB in 14 patients (70%), IVA in 3 (15%) and Ⅲ in 3 (15%). Four patients (21%) achieved a complete response, and 3 (15.7%), a partial response; an overall response rate was 36.7%. The median time to progression of the tumor was 33.8 weeks, and 1-year survival rate of the patients was 43.3%. Anemia of WHO grade Ⅲ or Ⅳ was seen in 2 patients (10%) and 1 patient (5%), respectively. Grade Ⅲ neutropenia and thrombocytopenia were observed in 2 patients (10%) and 1 patient (5%), respectively. CONCLUSION: With mild toxicity, combined chemotherapy of gemcitabine and carhoplatin is effective in the treatment of advanced gallbladder carcinoma.展开更多
Objective:The objective of this open-label,randomized study was to compare dose-dense paclitaxel plus carboplatin(PCdd)with dose-dense epirubicin and cyclophosphamide followed by paclitaxel(ECdd-P)as an adjuvant chemo...Objective:The objective of this open-label,randomized study was to compare dose-dense paclitaxel plus carboplatin(PCdd)with dose-dense epirubicin and cyclophosphamide followed by paclitaxel(ECdd-P)as an adjuvant chemotherapy for early triple-negative breast cancer(TNBC).Methods:We included Chinese patients with high recurrence risk TNBC who underwent primary breast cancer surgery.They were randomly assigned to receive PCdd[paclitaxel 150 mg/m2 on d 1 and carboplatin,the area under the curve,(AUC)=3 on d 2]or ECdd-P(epirubicin 80 mg/m2 divided in 2 d and cyclophosphamide 600 mg/m2 on d 1 for 4 cycles followed by paclitaxel 175 mg/m2 on d 1 for 4 cycles)every 2 weeks with granulocyte colony-stimulating factor(G-CSF)support.The primary endpoint was 3-year disease-free survival(DFS);the secondary endpoints were overall survival(OS)and safety.Results:The intent-to-treat population included 143 patients(70 in the PCdd arm and 73 in the ECdd-P arm).Compared with the ECdd-P arm,the PCdd arm had significantly higher 3-year DFS[93.9%vs.79.1%;hazard ratio(HR)=0.310;95%confidence interval(95%CI),0.137-0.704;log-rank,P=0.005]and OS(98.5%vs.92.9%;HR=0.142;95%CI,0.060-0.825;log-rank,P=0.028).Worse neutropenia(grade 3/4)was found in the ECdd-P than the PCdd arm(47.9%V5.21.4%,P=0.001).Conclusions:PCdd was superior to ECdd-P as an adjuvant chemotherapy for early TNBC with respect to improving the 3-year DFS and OS.PCdd also yielded lower hematological toxicity.Thus,PCdd might be a preferred regimen for early TNBC patients with a high recurrence risk.展开更多
Background: This retrospective study was to evaluate the efficacy and toxicity of gemcitabine plus carboplatin (GC regimen) and paclitaxel plus carboplatin (PC regimen) combination chemotherapy administered as an adju...Background: This retrospective study was to evaluate the efficacy and toxicity of gemcitabine plus carboplatin (GC regimen) and paclitaxel plus carboplatin (PC regimen) combination chemotherapy administered as an adjuvant therapy after complete resection of non-small cell lung cancer. Methods: Forty-four patients (GC regimen, n = 29;PC regimen, n = 15) received gemcitabine at a dose of 1000 mg/m2 on days 1 and 8, and carboplatin with the target dose of area under the curve (AUC) of 4 on day 8 every 28 days and paclitaxel at a dose of 70 mg/m2 on days 1, 8 and 15, and carboplatin with the target dose of AUC of 5 on day 1 every 28 days. Results: A total of 130 cycles of the treatment were administered (averaged, 3.1 in GC arm and 2.7 cycles in PC arm). Forty-three patients (97.7%) completed the scheduled cycles. One patient (2.3%) was discontinued due to grade 4 pneumonia. The dose was reduced in 2 patients (4.5%) due to grade 4 thrombocytopenia. Grade 3/4 neutropenia was significantly observed in the PC group (GC: 12/29, 41.4%;PC: 11/15, 73.3%, p = 0.0443). The nonhematological toxicities were mild. Grade 1/2 alanine aminotransferase and aspartate aminotransferase in the GC group was significantly observed higher compared to those of the PC group (GC: 20/29, 69.0%;PC: 4/15, 26.7%, p = 0.0076). Grade 1/2 alopecia was significantly observed in the PC group (GC: 0/25, 0.0%;PC: 13/15, 86.7%, p 0.0001). There was no treatment-related death. The median survival time (MST) of the entire GC group was 784 days, the 3-year overall survival (OS) was 75.9%, and 3-year recurrence-free survival (RFS) was 65.5%. The MST of the entire PC group was 963 days, the 3-year OS was 80.0%, and the 3-year RFS was 60.0%. Conclusion: These results demonstrate that the GC and PC combination chemotherapies are efficacious and feasible regimens, which should be considered as one of the standard therapies for adjuvant therapy.展开更多
<strong>Introduction: </strong><span style="font-family:""><span style="font-family:Verdana;">Epithelial Ovarian Carcinoma (EOC) comprises the vast majority (almost 90%...<strong>Introduction: </strong><span style="font-family:""><span style="font-family:Verdana;">Epithelial Ovarian Carcinoma (EOC) comprises the vast majority (almost 90%) of ovarian carcinomas. Chemotherapy is the main treatment in ovarian cancers. The standard of care in the chemotherapeutic is the combination of a platinum (carboplatin or cisplatin) and a taxane (paclitaxel or docetaxel). Studies were done to determine whether this combination to be given weekly or every 3 weeks. </span><b><span style="font-family:Verdana;">Patient and Method: </span></b><span style="font-family:Verdana;">Inclusion criteria: 1) Female patients between the ages of 17 - 78 years. 2) Baseline hematological, renal and liver laboratory profiles were within accepted ranges. 3) Performance status of the patients was 0-II. 4) Patients were pathologically proven ovarian cancer. 5) A follow-up period for at least 6 months was required. Exclusion criteria: 1) Patients who had double malignancy were excluded. 2) Performance status more than II. 3) Other comorbidity. </span><b><span style="font-family:Verdana;">Results: </span></b><span style="font-family:Verdana;">We reviewed 69 female patients with EOC, with 60% received every three weeks regimen. Mean age was 53.22 years. At a median follow up of 45.9 months, there was no significant different between the two protocols in terms of mean PFS, 62.35 months (95% CI: 50.08 - 74.63 months) for the three-weekly cohort, and 69.25 months (95% CI: 55.24 - 83.26 months) for weekly protocol (p = 0.613). The three weekly regimen patients had a higher incidence of hospital admission (40% vs 18.5% for the weekly protocol patients), but it didn’t reach a statistical significance (p = 0.063). The three weekly protocol had a significantly higher incidence of causing a neutropenic fever (p = 0.003). </span><b><span style="font-family:Verdana;">Conclusion: </span></b><span style="font-family:Verdana;">In our cohort of Egyptian women with EOC, no significant difference in PFS was found when compared the weekly Carboplatin/paclitaxel when compared to the classic three weeks, although the weekly protocol may be causing less febrile neutropenia and fewer hospital admissions.</span></span>展开更多
Background and objectives: Surgery is the primary therapy for localized gastric cancer, but even with the best results only 40% 5-year survival can be achieved with the use of postoperative adjuvant chemoradiotherapy....Background and objectives: Surgery is the primary therapy for localized gastric cancer, but even with the best results only 40% 5-year survival can be achieved with the use of postoperative adjuvant chemoradiotherapy. Preoperative therapy might help increase the R0 resection rate, which is an independent predictor of 5-year OS. Our study hypothesized that the concurrent combination of carboplatin-paclitaxel with radiation therapy would result in a pathological CR rate, which will be in turn associated with OAS and DFS benefits. Patients and methods: prospective phase II study included 32 patients with locally advanced gastric adenocarcinoma including gastroesophageal junction who received a combination of neoadjuvant conformal radiotherapy concurrently with carboplatin-paclitaxel followed by surgery. Results: Pathological CR and R0 resection rates were 18.8% and 75% respectively. With a median follow up of 24 months, 2 years disease-free survival was 28.1% and overall survival was 51.3%. The regimen was tolerated with neither grade 4 toxicities nor deaths. Conclusion: Neoadjuvant radiotherapy concomitant with carboplatin-paclitaxel chemotherapy is a well-tolerated approach for patients with locally advanced gastric adenocarcinoma resulting in significant pathological CR and R0 resection margins as reflected by the good DFS and OS.展开更多
AIM: To assess the efficacy and safety of the combination of pegylated liposomal doxorubicin(PLD) and carboplatin in patients with recurrent epithelial ovarian carcinoma(ROC), following disease progression on single a...AIM: To assess the efficacy and safety of the combination of pegylated liposomal doxorubicin(PLD) and carboplatin in patients with recurrent epithelial ovarian carcinoma(ROC), following disease progression on single agent PLD. METHODS: An analysis of the medical records of 10 patients with ROC, treated in our institution with a combination of PLD and carboplatin following progression on single-agent PLD therapy was performed. The median age was 59.1 years(range, 45 to 77 years). All diagnoses were histological-proven. Eight of the 10 patients were platinum-resistant. Following disease progression on single-agent PLD treatment, carboplatin area under the curve(AUC)-5 was added to PLD in all 10 patients. In order to assess disease status, Ca-125 was assessed before each PLD/carboplatin treatment. Relative changes in Ca-125 values were calculated, and response defined as a greater than 50% reduction in Ca-125 from baseline. Radiographic studies were reevaluated and responses to therapy based on com-puter tomography(CT) scans carried out on a regular basis every 2-3 mo in each patient. Statistical analysis was performed using SPSS(V19).RESULTS: A median of 10 cycles(range, 2-26) of the carboplatin-PLD combination was given. Of the 10 treated patients, 6 had > 50% reduction in Ca-125 levels from baseline, 4 of these had a partial response according to Response Evaluation Criteria in Solid Tumors(RECIST) criteria, and the other 2 patients had no measurable disease. In a further 2 patients with a best response of disease stabilization and < 50% reduction of Ca-125 levels, one had progression of disease after 26 cycles, and the second progressed with brain metastases following 12 cycles. Seven of the eight patients who were platinum-resistant showed evidence of clinical benefit on carboplatin-PLD combination therapy; 5 of these had > 50% reduction in Ca-125 level, 4 also showed a partial response on CT scan. The treatment was generally well-tolerated by the patients. CONCLUSION: Addition of carboplatin to PLD, after disease progression on single-agent PLD therapy, is both effective and safe in patients with ROC, even in those with Platinum-resistant disease.展开更多
To improve therapeutic effect and reduce severely side effects of carboplatin(CBP),the gas-generating nanocapsules were developed to accelerate CBP lysosome release and nucleus delivery.CBP/SB-NC was prepared by co-lo...To improve therapeutic effect and reduce severely side effects of carboplatin(CBP),the gas-generating nanocapsules were developed to accelerate CBP lysosome release and nucleus delivery.CBP/SB-NC was prepared by co-loading CBP and NaHCO 3(SB)in nanocapsules using w/o/w emulsification solvent evaporation.They exhibited vesicle-like spherical morphology,uniform particle size and negative zeta potential.Reaching the tumor site with a relatively high concentration is the first step for CBP delivery and the results showed that CBP/SB-NC could effectively increase drug accumulation at tumor site.After that,the drug delivery carriers need to be internalized into tumor cells and the in vitro cellular uptake ability results showed CBP/SB-NC could be internalized into RM-1 cells more efficient than CBP solution.After internalized by RM-1 cells,the gas-blasting release process was tested in acid environment.It was demonstrated that 5 mg/ml NaHCO 3 was optimal to achieve pH-responsive gas-blasting release.In vitro release results showed that CBP significantly rapid release in acid environment(pH 5.0)compared to neutral pH(pH 7.4)(P<0.05).Meanwhile,TEM and the change of the concentration of H+results exhibited that the explosion of CBP/SB 5-NC was more easily happened in lysosome acid environment(pH 5.0).The blasting release can accelerate CBP lysosome release to cytoplasm.Furthermore,the nucleus delivery results showed CBP/SB 5-NC can promote pH-triggered rapid nucleus delivery.And the results of Pt-DNA adduct assay showed that the binding efficiency between CBP and DNA of CBP/SB 5-NC was higher than CBP solution.At last,in vitro and in vivo anti-tumor efficacy proved that CBP/SB 5-NC could enhance anti-tumor activity for prostate cancer therapy.CBP/SB 5-NC also showed superior safety in vitro and in vivo by hemolysis assay and histopathological study.All of the results demonstrate that CBP/SB 5-NC would be an efficient gas-blasting release formulation to enhance prostate cancer treatment.展开更多
据美国BIOCOMPARE科技新闻网（2007／6／15）报道，一篇发表于6月6日的《国立癌症研究院期刊》（Journal of the National Cancer Institute）研究报告称，研究人员发现有些末期的非小细胞性肺癌（NSCLC）患者接受cisplatin治疗的存活率...据美国BIOCOMPARE科技新闻网（2007／6／15）报道，一篇发表于6月6日的《国立癌症研究院期刊》（Journal of the National Cancer Institute）研究报告称，研究人员发现有些末期的非小细胞性肺癌（NSCLC）患者接受cisplatin治疗的存活率较carboplatin高。展开更多
AIM: To evaluate the safety and efficacy of posterior sub-Tenon's carboplatin injection compared to intravitreal melphalan injection in the management of retinoblastoma(RB) with secondary vitreous seeds. The outco...AIM: To evaluate the safety and efficacy of posterior sub-Tenon's carboplatin injection compared to intravitreal melphalan injection in the management of retinoblastoma(RB) with secondary vitreous seeds. The outcome measures were vitreous seeds regression, need for other treatment modalities to achieve ocular salvage and treatment side effects.METHODS: A prospective interventional comparative nonrandomized study included RB eyes developed secondary vitreous seeds during the period of follow up. They subdivided into two groups: study group I where posterior sub-Tenon's carboplatin(20 mg/2 m L) was injected and study group II where intravitreal melphalan(20 μg/0.1 m L) was injected. The injections repeated every 2-4 wk.RESULTS: Thirty-three eyes were included in the study. Seventeen eyes(16 patients) in study group I and 16 eyes(16 patients) in study group II. Ten eyes(30.3%) were completely salvaged following local chemotherapies. Ocular salvage was 23.5% following posterior sub-Tenon's carboplatin injection versus 37.5% following intravitreal melphalan raised to 47.1% and 75% with addition of external beam radiotherapy(EBR) with no statistically significant difference between the study groups(P=0.16). A statistically significant correlation was found between ocular salvage rate and type of vitreous seeds either dust, spheres and clouds(r=0.42, P=0.015) and eyes harbor new solid tumor growth(r=0.35, P=0.045). The mean and median follow up periods following local chemotherapy injections were 2.0 y in the study group I and 2.37 y in the study group II. Few complications were reported: periorbital edema in all eyes and ocular motility disturbances in 13 eyes(76.5%) following posterior sub-Tenon's carboplatin injection. Vitreous hemorrhage developed in 2 eyes(12.5%) and localized retinopathy in 5 eyes(31.25%) following intravitreal melphalan.CONCLUSION: Local chemotherapy for treatment of RB with secondary vitreous seeds is safe and can salvage 30.3% of eyes without EBR. There is a superiority of intravitreal melphalan in ocular salvage however, no statistically significant difference between both groups.展开更多
AIM: To investigate the development of a safer chemotherapeutic regimen with better compliance, a total of 67 patients were enrolled as a single arm in a twostage multi-center phase Ⅱ study.METHODS: The patients rece...AIM: To investigate the development of a safer chemotherapeutic regimen with better compliance, a total of 67 patients were enrolled as a single arm in a twostage multi-center phase Ⅱ study.METHODS: The patients received chemotherapy with carboplatin(CBDCA) with an area under the curve(AUC) of 5, and docetaxel(DTX) at 60 mg/m2 tri-weekly for three cycles after surgery. The primary endpoint of this study was compliance, while the secondary endpoints were the adverse events(AE) and recurrencefree survival(RFS).RESULTS: Sixty-one patients were treated in this study arm. The patients were 43 males and 18 females, with a median age of 64.6 years. Fifty-one patients(83.6%)completed all three cycles of therapy. The presence of Grade 3 and 4 neutropenia was noted in 25% and 66%of the patients, respectively. The non-hematological AE were less frequently reported, and no treatmentrelated death was registered. The two-year RFS and OS rates of the 61 patients were 69.8% and 88.3%,respectively.CONCLUSION: A tri-weekly schedule of CBDCA and DTX as adjuvant chemotherapy showed a favorable feasibility.展开更多
Background: This retrospective study was to evaluate the efficacy and toxicity of gemcitabine plus carboplatin (GC regimen) and paclitaxel plus carboplatin (PC regimen) combination chemotherapy in elderly patients wit...Background: This retrospective study was to evaluate the efficacy and toxicity of gemcitabine plus carboplatin (GC regimen) and paclitaxel plus carboplatin (PC regimen) combination chemotherapy in elderly patients with non-small cell lung cancer. Methods: Seventy-four patients (GC regimen, n = 44;PC regimen, n= 30) received gemcitabine at a dose of 1000 mg/m2 on days 1 and 8, and carboplatin with the target dose of area under the curve (AUC) of 4 on day 8 every 28 days and paclitaxel at a dose of 70 mg/m2 on days 1, 8 and 15, and carboplatin with the target dose of AUC of 5 on day 1 every 28 days. Patients were divided in two groups (younger one: n = 42, old;elderly one: n= 32, ≥70 years old). Results: A total of 222 cycles of the treatment wasadministered. Seventy-one patients (95.9%) completed the scheduled cycles. Two patients in the elderly group were discontinued (6.3%) due to hematological toxicity and melena in the GC regimen and to grade 4 pneumonia in the PC regimen. The dose was reduced in 8 patients (10.8%) due to grade 4 thrombocytopenia. Grade 3/4 neutropenia was not significantly observed in both groups (younger group: 24/42, 57.1%;elderly group: 19/32, 59.4%, p = 0.8471). The nonhematological toxicities were mild in both groups. However, in theelderly group, grade 3/4 thrombocytopenia was significantly observed in the GC group (GC: 5/17, 29.4%;PC: 0/15, 0.0%, p = 0.0222). There was no treatment-related death. Conclusion: These results demonstrate that the GC and PC combination chemotherapies are efficacious and feasible regimens for lung cancer therapy, especially, both regimens should be considered as one of the standard therapies for elderly patients during lung cancer therapy.展开更多
The standard chemotherapy for Chinese elderly patients with non-small cell lung cancer (NSCLC) remains undefined. The study was to evaluate the therapeutic effects as well as side effects of pemetrexed plus carboplati...The standard chemotherapy for Chinese elderly patients with non-small cell lung cancer (NSCLC) remains undefined. The study was to evaluate the therapeutic effects as well as side effects of pemetrexed plus carboplatin regimen as the first-line therapy for Chinese elderly patients with advanced lung adenocarcinoma. Twenty-three Chinese elderly patients (male 14 and female 9, average age 73.7 years, range 70~81 years) with advanced lung adenocarcinoma received pemetrexed plus carboplatin as the first-line therapy, in detail, pemetrexed 500 mg/m2 and carboplatin AUC 5 mg/ml/m2 were given intravenously on day 1. The treatment was repeated everyday in the 21 days cycle. Therapeutic effects were evaluated at least after two cycles of treatment. The remission rate, disease control rate, time to progression and overall survival were observed. The results showed that all the cases were valid for response evaluation, with the complete remission 0 case, partial remission 8 cases, stabilize disease 9 cases and progression disease 6 cases. The remission rate (including complete remission and partial remission) was 34.8%, disease control rate 73.9%, the time to progression was 5.8 months and the overall survival 13.7 months. There showed the positive relationship between the curative effects (either time to progression or overall survival) and chemotherapy cycles. The main toxicities were bone marrow suppression, nausea and vomiting. There was no chemotherapy-related death. The data suggested that the combination regimen with pemetrexed plus carboplatin is an active and tolerable treatment plan for Chinese elderly patients with advanced lung adenocarcinoma, in which the side effects were tolerable and manageable.展开更多
We retrospectively reviewed the outcome of docetaxel, EMP, and carboplatin (DEC) as second-line chemotherapy in castration-resistant prostate cancer (CRPC) patients previously treated with docetaxel-prednisolone (DP)....We retrospectively reviewed the outcome of docetaxel, EMP, and carboplatin (DEC) as second-line chemotherapy in castration-resistant prostate cancer (CRPC) patients previously treated with docetaxel-prednisolone (DP). Nineteen patients pretreated with DP received a DEC regimen which consisted of a 28-day cycle of docetaxel [60 mg/m<sup>2</sup> intravenously (IV) on day 1)], carboplatin (IV to an area under the curve of 5 on day 1), and EMP (560 mg orally daily). The DEC therapy was continued intermittently after two consecutive courses. End points were DEC effect on prostate-specific antigen (PSA), radiographic response, progression-free survival (PFS), and overall survival (OS). All patients received DP before DEC administration with a median of 6 cycles (range, 1 - 12). Mean follow-up duration was 19.0 months after starting DEC therapy;median total number of the therapy cycles was 2 (range, 1 - 11). Thirteen patients (68.4%) showed a PSA decrease;6 (31.6%) showed a decrease in the PSA level of ≥50%, including 4 with no PSA response to DP. Grade 3/4 neutropenia and febrile neutropenia were observed in 13 (68.4%) and 2 (10.5%) patients, respectively. The median PFS following DEC was 3.7 months. The median OS was 18.0 months. In univariate analyses, patients with ≤12 months from CRPC to DEC had shorter PFS and OS, whereas PSA response to DP was not associated with PFS or OS in CRPC patients treated with DEC after DP. In conclusion, DEC retains some clinical benefits for CRPC patients pretreated with DP, even in patients without any response to DP. Therefore, they may be an effective and feasible treatment option for CRPC patients after first-line docetaxel therapy, particularly for those deemed unfit for novel endocrine and chemotherapeutic drugs.展开更多
Patients with non-small cell lung cancer (NSCLC) who have received more than one cycle of platinum-based chemotherapy in their lifetime may be at risk of hypersensitivity. The overall incidence of hypersensitivity to ...Patients with non-small cell lung cancer (NSCLC) who have received more than one cycle of platinum-based chemotherapy in their lifetime may be at risk of hypersensitivity. The overall incidence of hypersensitivity to carboplatin ranges from 1% to 27% and that of hypersensitivity to carboplatin is between 5% and 20%. However, the actual incidence of cross-reactivity between platinum salts has not yet been known. In this paper, we reported a case of a 39-year-old man with advanced non-small cell lung cancer, who had cisplatin anaphylaxis after having had carboplatin hypersensitivity at the previous cycle. The anaphylactic reaction was managed successfully with adrenaline, corticosteroids, antihistamines, oxygen mask and isotonic fluid support. No further reactions were observed and after that he stopped the platinum regimen. This case illustrates that NSCLC patients may experience hypersensitive and cross-reactivity to both carboplatin and cisplatin. It is important to be aware of the possibility of anaphylaxis so that appropriate premedication or effective treatment can be promptly instituted.展开更多
Objective:To study the clinical efficacy and effect on serum HE4, SMRP, CA125, CA199, B7-H4, TPS of carboplatin combined with paclitaxel for patients with ovarian cancer.Methods:A total of 80 patients with ovarian can...Objective:To study the clinical efficacy and effect on serum HE4, SMRP, CA125, CA199, B7-H4, TPS of carboplatin combined with paclitaxel for patients with ovarian cancer.Methods:A total of 80 patients with ovarian cancer in our hospital from December 2014 to December 2016 were enrolled in this study. The subjects were divided into the control group (n=40) and the treatment group (n=40) randomly. The control group was treated with carboplatin;the treatment group was treated with carboplatin combined with paclitaxel. 21 d for a period of treatment and the two groups were treated for 2 periods. The serum HE4, SMRP, CA125, CA199, B7-H4, TPS levels of the two groups before and after treatment was compared. Results:There were no significantly differences of the serum HE4, SMRP, CA125, CA199, B7-H4, TPS levels of the two groups before treatment. The serum HE4, SMRP, CA125, CA199, B7-H4, TPS levels of the two groups after treatment were significantly lower than before treatment, and that of the treatment group were significantly lower than that of the control group.Conclusion: Carboplatin combined with paclitaxe for patients with ovarian cancer can significantly reduce the serum HE4, SMRP, CA125, CA199, B7-H4, TPS levels;can be used for the prognosis of patients with ovarian cancer after treatment.展开更多
Objective: To evaluate the efficacy and safety of nedaplatin/gemcitabine (NG) and carboplatin/gemcitabine (CG) in the management of untreated advanced non‐small cell lung cancer (NSCLC). Methods: Sixty‐two patients ...Objective: To evaluate the efficacy and safety of nedaplatin/gemcitabine (NG) and carboplatin/gemcitabine (CG) in the management of untreated advanced non‐small cell lung cancer (NSCLC). Methods: Sixty‐two patients with previously untreated advanced NSCLC were recruited between June 2006 and November 2007. Subjects were randomly assigned to the NG arm (n=30) and the CG arm (n=32). Only patients (24 and 25 in the NG and CG arms, respectively) who completed ≥2 chemotherapy cycles were included in the data analysis. The primary outcome measure was the objective response rate (ORR). The secondary outcome measures included progression‐free survival (PFS), overall survival (OS) and adverse events. Results: There were no statistically significant differences in the efficacy measures (ORR, P=0.305; median PFS, P=0.198; median OS, P=0.961) or in the major adverse events (grade 3/4 neutropenia, P=0.666; grade 3/4 anemia, P=0.263; grade 3/4 thrombocytopenia, P=0.212) between the two treatment arms. However, there was a trend towards higher ORR (37.5% vs. 24.0%), longer PFS (6.0 vs. 5.0 months), and less adverse events in the NG arm. Conclusion: NG regimen seems to be superior over CG regimen for advance NSCLS, but further investigation is needed to validate this superiority.展开更多
Objective: This phase Ⅰ study was to evaluate safety, maximum tolerated dose, pharmacokinetics and preliminary antitumor activity of chidamide, a novel subtype-selective histone deacetylase(HDAC) inhibitor, in combin...Objective: This phase Ⅰ study was to evaluate safety, maximum tolerated dose, pharmacokinetics and preliminary antitumor activity of chidamide, a novel subtype-selective histone deacetylase(HDAC) inhibitor, in combination with paclitaxel and carboplatin in patients with advanced non-small cell lung cancer(NSCLC).Methods: Ten patients received oral chidamide 20, 25, or 30 mg twice per week continuously with paclitaxel(175 mg/m^2) and carboplatin [area under the curve(AUC) 5 mg/m L/min] administered in a 3-week cycle. Patients with response and stable disease after four cycles maintained chidamide monotherapy until disease progression or unacceptable toxicity. Blood samples were collected for pharmacokinetic analysis after the first single oral of chidamide and first combination treatment in cycle 1 from all patients.Results: Two dose-limiting toxicities were recorded in the 30 mg cohort, including thrombocytopenia and prolonged neutropenia in the first cycle. Grade 3/4 neutropenia in any cycle was observed in all patients, but was not associated with significant complications. Other grade 3/4 hematologic toxicities included thrombocytopenia and leucopenia. No significant changes were observed in pharmacokinetic parameters for both chidamide and paclitaxel. One patient in the 20 mg cohort had confirmed partial response(PR). Two out of 5 patients with brain metastases had intracranial complete remission after 4-cycle treatment.Conclusions: Chidamide combined with paclitaxel and carboplatin was generally tolerated without unanticipated toxicities or clinically relevant pharmacokinetic interactions. The recommended dose for chidamide in this combination was established at 20 mg, and a phase Ⅱ trial is ongoing with this regimen in patients with advanced NSCLC.展开更多
文摘Carboplatin, a second-generation platinum chemotherapeutic drug, is considerably less ototoxic than cisplatin. While common laboratory species such as mice, guinea pigs and rats are highly resistant to carboplatin ototoxicity, the chinchilla stands out as highly susceptible. Moreover, carboplatin causes an unusual gradient of cell death in chinchillas. Moderate doses selectively damage type I spiral ganglion neurons (SGN) and inner hair cells (IHC) and the lesion tends to be relatively uniform along the length of the cochlea. Higher doses eventually damage outer hair cells (OHC), but the lesion follows the traditional gradient in which damage is more severe in the base than the apex. While carboplatin ototoxicity has been well documented in adult animals in vivo, little is known about its in vitro toxicity. To elucidate the ototoxic effects of carboplatin in vitro, we prepared cochlear and vestibular organotypic cultures from postnatal day 3 rats and adult chinchillas. Chinchilla cochlear and vestibular cultures were treated with carboplatin concentrations ranging from 50 μM to 10 mM for 48 h. Consistent with in vivo data, carboplatin selectively damaged IHC at low concentrations (50-100 μM). Surprisingly, IHC loss decreased at higher doses and IHC were intact at doses exceeding 500 μM. The mechanisms underlying this nonlinear response are unclear but could be related to a decrease in carboplatin uptake via active transport mechanisms (e.g., copper). Unlike the cochlea, the carboplatin dose-response function increased with dose with the highest dose destroying all chinchilla vestibular hair cells. Cochlear hair cells and auditory nerve fibers in rat cochlear organotypic cultures were unaffected by carboplatin concentrations <10 μM; however, the damage in OHC were more severe than IHC once the dose reached 100 μM. A dose at 500 μM destroyed all the cochlear hair cells, but hair cell loss decreased at high concentrations and nearly all the cochlear hair cells were present at the highest dose, 5 mM. Unlike the nonlinear dose-response seen with cochlear hair cells, rat auditory nerve fiber and spiral ganglion losses increased with doses above 50 μM with the highest dose destroying virtually all SGN. The remarkable species differences seen in vitro suggest that chinchilla IHC and type I SGN posse some unique biological mechanism that makes them especially vulnerable to carboplatin toxicity.
文摘BACKGROUND: Patients with carcinoma of the gallbladder have advanced, unresectable tumor at the time of presentation and face a dismal prognosis in the absence of a standard palliative chemotherapy regimen. This study was undertaken to evaluate the efficacy and safety of combined chemotherapy of gemcitabine and carboplatin in 20 patients with advanced gallbladder carcinoma. METHODS: The criteria of eligibility included chemonaive patients with unresectable gallbladder cancer, bidimensionaIly measurable disease, Zubrod’s performance status≤2, and adequate major organ function. The patients received gemcitabine (1000 mg/m^2) on days 1 and 8, and carboplatin (target AUC of 5.0 mg/ml) on day 1, in a 21-day cycle. CT was used for response assessment. RESULTS: In this group of 20 patients with advanced gallbladder carcinoma 6 were men and 14 women, with a median age of 55 years. The stage of the tumor at presentation was IVB in 14 patients (70%), IVA in 3 (15%) and Ⅲ in 3 (15%). Four patients (21%) achieved a complete response, and 3 (15.7%), a partial response; an overall response rate was 36.7%. The median time to progression of the tumor was 33.8 weeks, and 1-year survival rate of the patients was 43.3%. Anemia of WHO grade Ⅲ or Ⅳ was seen in 2 patients (10%) and 1 patient (5%), respectively. Grade Ⅲ neutropenia and thrombocytopenia were observed in 2 patients (10%) and 1 patient (5%), respectively. CONCLUSION: With mild toxicity, combined chemotherapy of gemcitabine and carhoplatin is effective in the treatment of advanced gallbladder carcinoma.
基金This work was supported by National Key Research and Development Program of China(No.2O18YFC13121O1)Chinese Academy of Medical Science Initiative for Innovative Medicine(No.CAMS-2016-I2M-1-010).
文摘Objective:The objective of this open-label,randomized study was to compare dose-dense paclitaxel plus carboplatin(PCdd)with dose-dense epirubicin and cyclophosphamide followed by paclitaxel(ECdd-P)as an adjuvant chemotherapy for early triple-negative breast cancer(TNBC).Methods:We included Chinese patients with high recurrence risk TNBC who underwent primary breast cancer surgery.They were randomly assigned to receive PCdd[paclitaxel 150 mg/m2 on d 1 and carboplatin,the area under the curve,(AUC)=3 on d 2]or ECdd-P(epirubicin 80 mg/m2 divided in 2 d and cyclophosphamide 600 mg/m2 on d 1 for 4 cycles followed by paclitaxel 175 mg/m2 on d 1 for 4 cycles)every 2 weeks with granulocyte colony-stimulating factor(G-CSF)support.The primary endpoint was 3-year disease-free survival(DFS);the secondary endpoints were overall survival(OS)and safety.Results:The intent-to-treat population included 143 patients(70 in the PCdd arm and 73 in the ECdd-P arm).Compared with the ECdd-P arm,the PCdd arm had significantly higher 3-year DFS[93.9%vs.79.1%;hazard ratio(HR)=0.310;95%confidence interval(95%CI),0.137-0.704;log-rank,P=0.005]and OS(98.5%vs.92.9%;HR=0.142;95%CI,0.060-0.825;log-rank,P=0.028).Worse neutropenia(grade 3/4)was found in the ECdd-P than the PCdd arm(47.9%V5.21.4%,P=0.001).Conclusions:PCdd was superior to ECdd-P as an adjuvant chemotherapy for early TNBC with respect to improving the 3-year DFS and OS.PCdd also yielded lower hematological toxicity.Thus,PCdd might be a preferred regimen for early TNBC patients with a high recurrence risk.
文摘Background: This retrospective study was to evaluate the efficacy and toxicity of gemcitabine plus carboplatin (GC regimen) and paclitaxel plus carboplatin (PC regimen) combination chemotherapy administered as an adjuvant therapy after complete resection of non-small cell lung cancer. Methods: Forty-four patients (GC regimen, n = 29;PC regimen, n = 15) received gemcitabine at a dose of 1000 mg/m2 on days 1 and 8, and carboplatin with the target dose of area under the curve (AUC) of 4 on day 8 every 28 days and paclitaxel at a dose of 70 mg/m2 on days 1, 8 and 15, and carboplatin with the target dose of AUC of 5 on day 1 every 28 days. Results: A total of 130 cycles of the treatment were administered (averaged, 3.1 in GC arm and 2.7 cycles in PC arm). Forty-three patients (97.7%) completed the scheduled cycles. One patient (2.3%) was discontinued due to grade 4 pneumonia. The dose was reduced in 2 patients (4.5%) due to grade 4 thrombocytopenia. Grade 3/4 neutropenia was significantly observed in the PC group (GC: 12/29, 41.4%;PC: 11/15, 73.3%, p = 0.0443). The nonhematological toxicities were mild. Grade 1/2 alanine aminotransferase and aspartate aminotransferase in the GC group was significantly observed higher compared to those of the PC group (GC: 20/29, 69.0%;PC: 4/15, 26.7%, p = 0.0076). Grade 1/2 alopecia was significantly observed in the PC group (GC: 0/25, 0.0%;PC: 13/15, 86.7%, p 0.0001). There was no treatment-related death. The median survival time (MST) of the entire GC group was 784 days, the 3-year overall survival (OS) was 75.9%, and 3-year recurrence-free survival (RFS) was 65.5%. The MST of the entire PC group was 963 days, the 3-year OS was 80.0%, and the 3-year RFS was 60.0%. Conclusion: These results demonstrate that the GC and PC combination chemotherapies are efficacious and feasible regimens, which should be considered as one of the standard therapies for adjuvant therapy.
文摘<strong>Introduction: </strong><span style="font-family:""><span style="font-family:Verdana;">Epithelial Ovarian Carcinoma (EOC) comprises the vast majority (almost 90%) of ovarian carcinomas. Chemotherapy is the main treatment in ovarian cancers. The standard of care in the chemotherapeutic is the combination of a platinum (carboplatin or cisplatin) and a taxane (paclitaxel or docetaxel). Studies were done to determine whether this combination to be given weekly or every 3 weeks. </span><b><span style="font-family:Verdana;">Patient and Method: </span></b><span style="font-family:Verdana;">Inclusion criteria: 1) Female patients between the ages of 17 - 78 years. 2) Baseline hematological, renal and liver laboratory profiles were within accepted ranges. 3) Performance status of the patients was 0-II. 4) Patients were pathologically proven ovarian cancer. 5) A follow-up period for at least 6 months was required. Exclusion criteria: 1) Patients who had double malignancy were excluded. 2) Performance status more than II. 3) Other comorbidity. </span><b><span style="font-family:Verdana;">Results: </span></b><span style="font-family:Verdana;">We reviewed 69 female patients with EOC, with 60% received every three weeks regimen. Mean age was 53.22 years. At a median follow up of 45.9 months, there was no significant different between the two protocols in terms of mean PFS, 62.35 months (95% CI: 50.08 - 74.63 months) for the three-weekly cohort, and 69.25 months (95% CI: 55.24 - 83.26 months) for weekly protocol (p = 0.613). The three weekly regimen patients had a higher incidence of hospital admission (40% vs 18.5% for the weekly protocol patients), but it didn’t reach a statistical significance (p = 0.063). The three weekly protocol had a significantly higher incidence of causing a neutropenic fever (p = 0.003). </span><b><span style="font-family:Verdana;">Conclusion: </span></b><span style="font-family:Verdana;">In our cohort of Egyptian women with EOC, no significant difference in PFS was found when compared the weekly Carboplatin/paclitaxel when compared to the classic three weeks, although the weekly protocol may be causing less febrile neutropenia and fewer hospital admissions.</span></span>
文摘Background and objectives: Surgery is the primary therapy for localized gastric cancer, but even with the best results only 40% 5-year survival can be achieved with the use of postoperative adjuvant chemoradiotherapy. Preoperative therapy might help increase the R0 resection rate, which is an independent predictor of 5-year OS. Our study hypothesized that the concurrent combination of carboplatin-paclitaxel with radiation therapy would result in a pathological CR rate, which will be in turn associated with OAS and DFS benefits. Patients and methods: prospective phase II study included 32 patients with locally advanced gastric adenocarcinoma including gastroesophageal junction who received a combination of neoadjuvant conformal radiotherapy concurrently with carboplatin-paclitaxel followed by surgery. Results: Pathological CR and R0 resection rates were 18.8% and 75% respectively. With a median follow up of 24 months, 2 years disease-free survival was 28.1% and overall survival was 51.3%. The regimen was tolerated with neither grade 4 toxicities nor deaths. Conclusion: Neoadjuvant radiotherapy concomitant with carboplatin-paclitaxel chemotherapy is a well-tolerated approach for patients with locally advanced gastric adenocarcinoma resulting in significant pathological CR and R0 resection margins as reflected by the good DFS and OS.
文摘AIM: To assess the efficacy and safety of the combination of pegylated liposomal doxorubicin(PLD) and carboplatin in patients with recurrent epithelial ovarian carcinoma(ROC), following disease progression on single agent PLD. METHODS: An analysis of the medical records of 10 patients with ROC, treated in our institution with a combination of PLD and carboplatin following progression on single-agent PLD therapy was performed. The median age was 59.1 years(range, 45 to 77 years). All diagnoses were histological-proven. Eight of the 10 patients were platinum-resistant. Following disease progression on single-agent PLD treatment, carboplatin area under the curve(AUC)-5 was added to PLD in all 10 patients. In order to assess disease status, Ca-125 was assessed before each PLD/carboplatin treatment. Relative changes in Ca-125 values were calculated, and response defined as a greater than 50% reduction in Ca-125 from baseline. Radiographic studies were reevaluated and responses to therapy based on com-puter tomography(CT) scans carried out on a regular basis every 2-3 mo in each patient. Statistical analysis was performed using SPSS(V19).RESULTS: A median of 10 cycles(range, 2-26) of the carboplatin-PLD combination was given. Of the 10 treated patients, 6 had > 50% reduction in Ca-125 levels from baseline, 4 of these had a partial response according to Response Evaluation Criteria in Solid Tumors(RECIST) criteria, and the other 2 patients had no measurable disease. In a further 2 patients with a best response of disease stabilization and < 50% reduction of Ca-125 levels, one had progression of disease after 26 cycles, and the second progressed with brain metastases following 12 cycles. Seven of the eight patients who were platinum-resistant showed evidence of clinical benefit on carboplatin-PLD combination therapy; 5 of these had > 50% reduction in Ca-125 level, 4 also showed a partial response on CT scan. The treatment was generally well-tolerated by the patients. CONCLUSION: Addition of carboplatin to PLD, after disease progression on single-agent PLD therapy, is both effective and safe in patients with ROC, even in those with Platinum-resistant disease.
基金This work was supported by a grant from the National Natural Science Foundation of China(Nos.81773652 and 81974498)the Young Scholar Program of Shandong University(2017WLJH40).
文摘To improve therapeutic effect and reduce severely side effects of carboplatin(CBP),the gas-generating nanocapsules were developed to accelerate CBP lysosome release and nucleus delivery.CBP/SB-NC was prepared by co-loading CBP and NaHCO 3(SB)in nanocapsules using w/o/w emulsification solvent evaporation.They exhibited vesicle-like spherical morphology,uniform particle size and negative zeta potential.Reaching the tumor site with a relatively high concentration is the first step for CBP delivery and the results showed that CBP/SB-NC could effectively increase drug accumulation at tumor site.After that,the drug delivery carriers need to be internalized into tumor cells and the in vitro cellular uptake ability results showed CBP/SB-NC could be internalized into RM-1 cells more efficient than CBP solution.After internalized by RM-1 cells,the gas-blasting release process was tested in acid environment.It was demonstrated that 5 mg/ml NaHCO 3 was optimal to achieve pH-responsive gas-blasting release.In vitro release results showed that CBP significantly rapid release in acid environment(pH 5.0)compared to neutral pH(pH 7.4)(P<0.05).Meanwhile,TEM and the change of the concentration of H+results exhibited that the explosion of CBP/SB 5-NC was more easily happened in lysosome acid environment(pH 5.0).The blasting release can accelerate CBP lysosome release to cytoplasm.Furthermore,the nucleus delivery results showed CBP/SB 5-NC can promote pH-triggered rapid nucleus delivery.And the results of Pt-DNA adduct assay showed that the binding efficiency between CBP and DNA of CBP/SB 5-NC was higher than CBP solution.At last,in vitro and in vivo anti-tumor efficacy proved that CBP/SB 5-NC could enhance anti-tumor activity for prostate cancer therapy.CBP/SB 5-NC also showed superior safety in vitro and in vivo by hemolysis assay and histopathological study.All of the results demonstrate that CBP/SB 5-NC would be an efficient gas-blasting release formulation to enhance prostate cancer treatment.
文摘据美国BIOCOMPARE科技新闻网（2007／6／15）报道，一篇发表于6月6日的《国立癌症研究院期刊》（Journal of the National Cancer Institute）研究报告称，研究人员发现有些末期的非小细胞性肺癌（NSCLC）患者接受cisplatin治疗的存活率较carboplatin高。
文摘AIM: To evaluate the safety and efficacy of posterior sub-Tenon's carboplatin injection compared to intravitreal melphalan injection in the management of retinoblastoma(RB) with secondary vitreous seeds. The outcome measures were vitreous seeds regression, need for other treatment modalities to achieve ocular salvage and treatment side effects.METHODS: A prospective interventional comparative nonrandomized study included RB eyes developed secondary vitreous seeds during the period of follow up. They subdivided into two groups: study group I where posterior sub-Tenon's carboplatin(20 mg/2 m L) was injected and study group II where intravitreal melphalan(20 μg/0.1 m L) was injected. The injections repeated every 2-4 wk.RESULTS: Thirty-three eyes were included in the study. Seventeen eyes(16 patients) in study group I and 16 eyes(16 patients) in study group II. Ten eyes(30.3%) were completely salvaged following local chemotherapies. Ocular salvage was 23.5% following posterior sub-Tenon's carboplatin injection versus 37.5% following intravitreal melphalan raised to 47.1% and 75% with addition of external beam radiotherapy(EBR) with no statistically significant difference between the study groups(P=0.16). A statistically significant correlation was found between ocular salvage rate and type of vitreous seeds either dust, spheres and clouds(r=0.42, P=0.015) and eyes harbor new solid tumor growth(r=0.35, P=0.045). The mean and median follow up periods following local chemotherapy injections were 2.0 y in the study group I and 2.37 y in the study group II. Few complications were reported: periorbital edema in all eyes and ocular motility disturbances in 13 eyes(76.5%) following posterior sub-Tenon's carboplatin injection. Vitreous hemorrhage developed in 2 eyes(12.5%) and localized retinopathy in 5 eyes(31.25%) following intravitreal melphalan.CONCLUSION: Local chemotherapy for treatment of RB with secondary vitreous seeds is safe and can salvage 30.3% of eyes without EBR. There is a superiority of intravitreal melphalan in ocular salvage however, no statistically significant difference between both groups.
基金Supported by JPJS KAKENHI,No.25462202A UOEH Research Grant for Promotion of Occupational HealthUramoto H,Hanagiri T and Tanaka F received a research grant that belongs to the institute from Sanofi-Aventis,Inc
文摘AIM: To investigate the development of a safer chemotherapeutic regimen with better compliance, a total of 67 patients were enrolled as a single arm in a twostage multi-center phase Ⅱ study.METHODS: The patients received chemotherapy with carboplatin(CBDCA) with an area under the curve(AUC) of 5, and docetaxel(DTX) at 60 mg/m2 tri-weekly for three cycles after surgery. The primary endpoint of this study was compliance, while the secondary endpoints were the adverse events(AE) and recurrencefree survival(RFS).RESULTS: Sixty-one patients were treated in this study arm. The patients were 43 males and 18 females, with a median age of 64.6 years. Fifty-one patients(83.6%)completed all three cycles of therapy. The presence of Grade 3 and 4 neutropenia was noted in 25% and 66%of the patients, respectively. The non-hematological AE were less frequently reported, and no treatmentrelated death was registered. The two-year RFS and OS rates of the 61 patients were 69.8% and 88.3%,respectively.CONCLUSION: A tri-weekly schedule of CBDCA and DTX as adjuvant chemotherapy showed a favorable feasibility.
文摘Background: This retrospective study was to evaluate the efficacy and toxicity of gemcitabine plus carboplatin (GC regimen) and paclitaxel plus carboplatin (PC regimen) combination chemotherapy in elderly patients with non-small cell lung cancer. Methods: Seventy-four patients (GC regimen, n = 44;PC regimen, n= 30) received gemcitabine at a dose of 1000 mg/m2 on days 1 and 8, and carboplatin with the target dose of area under the curve (AUC) of 4 on day 8 every 28 days and paclitaxel at a dose of 70 mg/m2 on days 1, 8 and 15, and carboplatin with the target dose of AUC of 5 on day 1 every 28 days. Patients were divided in two groups (younger one: n = 42, old;elderly one: n= 32, ≥70 years old). Results: A total of 222 cycles of the treatment wasadministered. Seventy-one patients (95.9%) completed the scheduled cycles. Two patients in the elderly group were discontinued (6.3%) due to hematological toxicity and melena in the GC regimen and to grade 4 pneumonia in the PC regimen. The dose was reduced in 8 patients (10.8%) due to grade 4 thrombocytopenia. Grade 3/4 neutropenia was not significantly observed in both groups (younger group: 24/42, 57.1%;elderly group: 19/32, 59.4%, p = 0.8471). The nonhematological toxicities were mild in both groups. However, in theelderly group, grade 3/4 thrombocytopenia was significantly observed in the GC group (GC: 5/17, 29.4%;PC: 0/15, 0.0%, p = 0.0222). There was no treatment-related death. Conclusion: These results demonstrate that the GC and PC combination chemotherapies are efficacious and feasible regimens for lung cancer therapy, especially, both regimens should be considered as one of the standard therapies for elderly patients during lung cancer therapy.
文摘The standard chemotherapy for Chinese elderly patients with non-small cell lung cancer (NSCLC) remains undefined. The study was to evaluate the therapeutic effects as well as side effects of pemetrexed plus carboplatin regimen as the first-line therapy for Chinese elderly patients with advanced lung adenocarcinoma. Twenty-three Chinese elderly patients (male 14 and female 9, average age 73.7 years, range 70~81 years) with advanced lung adenocarcinoma received pemetrexed plus carboplatin as the first-line therapy, in detail, pemetrexed 500 mg/m2 and carboplatin AUC 5 mg/ml/m2 were given intravenously on day 1. The treatment was repeated everyday in the 21 days cycle. Therapeutic effects were evaluated at least after two cycles of treatment. The remission rate, disease control rate, time to progression and overall survival were observed. The results showed that all the cases were valid for response evaluation, with the complete remission 0 case, partial remission 8 cases, stabilize disease 9 cases and progression disease 6 cases. The remission rate (including complete remission and partial remission) was 34.8%, disease control rate 73.9%, the time to progression was 5.8 months and the overall survival 13.7 months. There showed the positive relationship between the curative effects (either time to progression or overall survival) and chemotherapy cycles. The main toxicities were bone marrow suppression, nausea and vomiting. There was no chemotherapy-related death. The data suggested that the combination regimen with pemetrexed plus carboplatin is an active and tolerable treatment plan for Chinese elderly patients with advanced lung adenocarcinoma, in which the side effects were tolerable and manageable.
文摘We retrospectively reviewed the outcome of docetaxel, EMP, and carboplatin (DEC) as second-line chemotherapy in castration-resistant prostate cancer (CRPC) patients previously treated with docetaxel-prednisolone (DP). Nineteen patients pretreated with DP received a DEC regimen which consisted of a 28-day cycle of docetaxel [60 mg/m<sup>2</sup> intravenously (IV) on day 1)], carboplatin (IV to an area under the curve of 5 on day 1), and EMP (560 mg orally daily). The DEC therapy was continued intermittently after two consecutive courses. End points were DEC effect on prostate-specific antigen (PSA), radiographic response, progression-free survival (PFS), and overall survival (OS). All patients received DP before DEC administration with a median of 6 cycles (range, 1 - 12). Mean follow-up duration was 19.0 months after starting DEC therapy;median total number of the therapy cycles was 2 (range, 1 - 11). Thirteen patients (68.4%) showed a PSA decrease;6 (31.6%) showed a decrease in the PSA level of ≥50%, including 4 with no PSA response to DP. Grade 3/4 neutropenia and febrile neutropenia were observed in 13 (68.4%) and 2 (10.5%) patients, respectively. The median PFS following DEC was 3.7 months. The median OS was 18.0 months. In univariate analyses, patients with ≤12 months from CRPC to DEC had shorter PFS and OS, whereas PSA response to DP was not associated with PFS or OS in CRPC patients treated with DEC after DP. In conclusion, DEC retains some clinical benefits for CRPC patients pretreated with DP, even in patients without any response to DP. Therefore, they may be an effective and feasible treatment option for CRPC patients after first-line docetaxel therapy, particularly for those deemed unfit for novel endocrine and chemotherapeutic drugs.
文摘Patients with non-small cell lung cancer (NSCLC) who have received more than one cycle of platinum-based chemotherapy in their lifetime may be at risk of hypersensitivity. The overall incidence of hypersensitivity to carboplatin ranges from 1% to 27% and that of hypersensitivity to carboplatin is between 5% and 20%. However, the actual incidence of cross-reactivity between platinum salts has not yet been known. In this paper, we reported a case of a 39-year-old man with advanced non-small cell lung cancer, who had cisplatin anaphylaxis after having had carboplatin hypersensitivity at the previous cycle. The anaphylactic reaction was managed successfully with adrenaline, corticosteroids, antihistamines, oxygen mask and isotonic fluid support. No further reactions were observed and after that he stopped the platinum regimen. This case illustrates that NSCLC patients may experience hypersensitive and cross-reactivity to both carboplatin and cisplatin. It is important to be aware of the possibility of anaphylaxis so that appropriate premedication or effective treatment can be promptly instituted.
基金Young Fund of Hubei Natural Science Foundation of China(2016CFB340)Basic Research Project of Wuhan Science and Technology Bureau(NO.2015061701011626)Key Project of Wuhan Municipal Health and Family Planning Commission(NO.WX15A08).
文摘Objective:To study the clinical efficacy and effect on serum HE4, SMRP, CA125, CA199, B7-H4, TPS of carboplatin combined with paclitaxel for patients with ovarian cancer.Methods:A total of 80 patients with ovarian cancer in our hospital from December 2014 to December 2016 were enrolled in this study. The subjects were divided into the control group (n=40) and the treatment group (n=40) randomly. The control group was treated with carboplatin;the treatment group was treated with carboplatin combined with paclitaxel. 21 d for a period of treatment and the two groups were treated for 2 periods. The serum HE4, SMRP, CA125, CA199, B7-H4, TPS levels of the two groups before and after treatment was compared. Results:There were no significantly differences of the serum HE4, SMRP, CA125, CA199, B7-H4, TPS levels of the two groups before treatment. The serum HE4, SMRP, CA125, CA199, B7-H4, TPS levels of the two groups after treatment were significantly lower than before treatment, and that of the treatment group were significantly lower than that of the control group.Conclusion: Carboplatin combined with paclitaxe for patients with ovarian cancer can significantly reduce the serum HE4, SMRP, CA125, CA199, B7-H4, TPS levels;can be used for the prognosis of patients with ovarian cancer after treatment.
文摘Objective: To evaluate the efficacy and safety of nedaplatin/gemcitabine (NG) and carboplatin/gemcitabine (CG) in the management of untreated advanced non‐small cell lung cancer (NSCLC). Methods: Sixty‐two patients with previously untreated advanced NSCLC were recruited between June 2006 and November 2007. Subjects were randomly assigned to the NG arm (n=30) and the CG arm (n=32). Only patients (24 and 25 in the NG and CG arms, respectively) who completed ≥2 chemotherapy cycles were included in the data analysis. The primary outcome measure was the objective response rate (ORR). The secondary outcome measures included progression‐free survival (PFS), overall survival (OS) and adverse events. Results: There were no statistically significant differences in the efficacy measures (ORR, P=0.305; median PFS, P=0.198; median OS, P=0.961) or in the major adverse events (grade 3/4 neutropenia, P=0.666; grade 3/4 anemia, P=0.263; grade 3/4 thrombocytopenia, P=0.212) between the two treatment arms. However, there was a trend towards higher ORR (37.5% vs. 24.0%), longer PFS (6.0 vs. 5.0 months), and less adverse events in the NG arm. Conclusion: NG regimen seems to be superior over CG regimen for advance NSCLS, but further investigation is needed to validate this superiority.
基金supported in part by grants from Chinese National Major Project for New Drug Innovation(2012ZX09303012-001)
文摘Objective: This phase Ⅰ study was to evaluate safety, maximum tolerated dose, pharmacokinetics and preliminary antitumor activity of chidamide, a novel subtype-selective histone deacetylase(HDAC) inhibitor, in combination with paclitaxel and carboplatin in patients with advanced non-small cell lung cancer(NSCLC).Methods: Ten patients received oral chidamide 20, 25, or 30 mg twice per week continuously with paclitaxel(175 mg/m^2) and carboplatin [area under the curve(AUC) 5 mg/m L/min] administered in a 3-week cycle. Patients with response and stable disease after four cycles maintained chidamide monotherapy until disease progression or unacceptable toxicity. Blood samples were collected for pharmacokinetic analysis after the first single oral of chidamide and first combination treatment in cycle 1 from all patients.Results: Two dose-limiting toxicities were recorded in the 30 mg cohort, including thrombocytopenia and prolonged neutropenia in the first cycle. Grade 3/4 neutropenia in any cycle was observed in all patients, but was not associated with significant complications. Other grade 3/4 hematologic toxicities included thrombocytopenia and leucopenia. No significant changes were observed in pharmacokinetic parameters for both chidamide and paclitaxel. One patient in the 20 mg cohort had confirmed partial response(PR). Two out of 5 patients with brain metastases had intracranial complete remission after 4-cycle treatment.Conclusions: Chidamide combined with paclitaxel and carboplatin was generally tolerated without unanticipated toxicities or clinically relevant pharmacokinetic interactions. The recommended dose for chidamide in this combination was established at 20 mg, and a phase Ⅱ trial is ongoing with this regimen in patients with advanced NSCLC.
