Efficacy and safety of the paclitaxel and carboplatin combination in patients with previously treated advanced ovarian carcinoma

Background: Platinum compounds are the most active drugs in ovarian cancer treatment; cisplatin and carboplatin demonstrated similar efficacies but different toxicity profiles. Paclitaxel combined with cisplatin as first-line treatment improved overall survival when compared to a cisplatin-cyclophosphamide combination, but generated higher rates of neutropenia, febrile neutropenia and neurotoxicity. The paclitaxel-carboplatin combination may be better tolerated than cisplatin–paclitaxel.Design: The objective of the present study was to assess the efficacy and safety of the combination of paclitaxel and carboplatin in previously treated advanced ovarian cancer patients.Patients and methods: During or after platinum-based chemotherapy, 73 patients with progressive advanced epithelial ovarian carcinoma were enrolled to receive every four weeks a three-hour infusion of paclitaxel 175 mg/m² followed by a 30-minute carboplatin infusion. The carboplatin dose was calculated to obtain the recommended area concentration-versus-time under the curve of 5 mg·ml^-1·min.Results: Toxicity and response could be evaluated for 72 and 62 patients, respectively. Eleven complete and 15 partial responses gave an overall response rate of 42% (95% CI: 30%–54%). Response rates for platinum-refractory patients and those with early (3 and <12 months) and late (>12 months) relapses were 24%, 33% and 70%, respectively. The respective median response duration, the median progression-free survival and median overall survival were 8, 6 and 14 months. Myelosuppression was the most frequent and severe toxicity. Grade 3 and 4 neutropenia occurred, respectively in 30% and 23% of the cycles; 6% of the cycles benefited from medullary growth factors. Only one episode of febrile neutropenia was observed. Grade 3 and 4 thrombocytopenia occurred, respectively during 3% and 1% of the cycles. Alopecia was frequent. Transient peripheral neuropathy developed in 47% of patients but was severe in only one patient. One early death was attributed to progressive disease and possibly to therapy.Conclusion: This combined paclitaxel–carboplatin therapy is effective and can be safely administered to ovarian cancer patients who relapse after one or two regimens of platinum-based chemotherapy.     

A phase I dose-finding study of a combination of pegylated liposomal doxorubicin (Doxil), carboplatin and paclitaxel in ovarian cancer

Standard chemotherapy for advanced epithelial ovarian cancer is a combination of platinum-paclitaxel. One strategy to improve the outcome for patients is to add other agents to standard therapy. Doxil is active in relapsed disease and has a response rate of 25% in platinum-resistant relapsed disease. A dose finding study of doxil-carboplatin-paclitaxel was therefore undertaken in women receiving first-line therapy. Thirty-one women with epithelial ovarian cancer or mixed Mullerian tumours of the ovary were enrolled. The doses of carboplatin, paclitaxel and doxil were as follows: carboplatin AUC 5 and 6; paclitaxel, 135 and 175 mg m(-2); doxil 20, 30, 40 and 50 mg m(-2). Schedules examined included treatment cycles of 21 and 28 days, and an alternating schedule of carboplatin-paclitaxel (q 21) with doxil being administered every other course (q 42). The dose-limiting toxicities were found to be neutropenia, stomatitis and palmar plantar syndrome and the maximum tolerated dose was defined as; carboplatin AUC 5, paclitaxel 175 mg m(-2) and doxil 30 mg m(-2) q 21. Reducing the paclitaxel dose to 135 mg m(-2) did not allow the doxil dose to be increased. Delivering doxil on alternate cycles at doses of 40 and 50 mg m(-2) also resulted in dose-limiting toxicities. The recommended doses for phase II/III trials are carboplatin AUC 6, paclitaxel 175 mg m(-2), doxil 30 mg m(-2) q 28 or carboplatin AUC 5, paclitaxel 175 mg m(-2), doxil 20 mg m(-2) q 21. Grade 3/4 haematologic toxicity was common at the recommended phase II doses but was short lived and not clinically important and non-haematologic toxicities were generally mild and consisted of nausea, paraesthesiae, stomatitis and palmar plantar syndrome.     

Phase II study of the combination carboplatin and paclitaxel in patients with ovarian cancer

Background: Recently the feasibility of combining carboplatin withpaclitaxel has been demonstrated in dose-finding studies. Maximum tolerateddoses were 550 mg/m² and 200 mg/m² (threehours), respectively. We report now a phase II study in ovarian cancerpatients.Patients and methods: Twenty-one chemo-naïve patients with optimally(n = 6) or suboptimally (n = 15) debulked stage III or IV ovarian cancer weretreated every three weeks for six courses with paclitaxel (200mg/m²) as a three-hour infusion, immediately followed bycarboplatin (550 mg/m²) as a 30-minute infusion.Results: Uncomplicated neutropenia was the principal toxicity, with mildanemia occurring regularly. As observed in the preceding phase I study, arelative lack of thrombocytopenia, generally grade III was found. Othertoxicities consisted of mild neurotoxicity, nausea and vomiting, alopecia,myalgia, and bone pain. All suboptimally debulked patients responded totherapy. Overall, 12 patients underwent second-look laparoscopy, whichrevealed a pathologically confirmed complete remission in six. The medianfollow-up interval at the time of analysis was 14 months. Twelve patients arecurrently free of progression, at 8+ to 19± months after the start oftherapy.Conclusion: The carboplatin/paclitaxel combination appears to be awell-tolerated regimen, yielding high response rates. This combination has nowgone forward to be evaluated in prospective randomized trials versus thecisplatin/paclitaxel combination.     

Phase I/II study of the combination of carboplatin and paclitaxel as first-line chemotherapy in patients with advanced epithelial ovarian cancer

Purpose: We performed a phase I/II study evaluating the combination ofpaclitaxel and carboplatin as first-line chemotherapy in patients withadvanced ovarian cancer. The aim of this study was to define a feasible andsafe combination regimen that could be recommended for future phase IIIstudies.Design: This study was a parallel two-arm, non-randomized, open trial. Ina first step, carboplatin was administered at a fixed dose of AUC 5 andpaclitaxel was escalated in 25 mg/m² steps starting at 135mg/m². Paclitaxel was given as a three-hour infusion.Carboplatin was administered on day 1 following paclitaxel in one study armand 24 hours after paclitaxel infusion on day 2 in the other study arm.Carboplatin was escalated to AUC 6 and AUC 7.5 after the MTD for paclitaxelhad been defined. Treatment was repeated every three weeks.Patients: Sixty-one patients with untreated histologically confirmedepithelial ovarian cancer were recruited of whom 59 were found eligible andevaluable for toxicity. Thirty-three patients with bidimensionally measurabledisease were evaluable for tumor response.Results: We could not detect any advantage of the two-day schedule comparedwith the more convenient one-day schedule. Dose limiting toxicities wereneutropenia, thrombocytopenia, and neurotoxicity. Except for two patients,toxicity was acceptable and clinically managable. One patient died ofneutropenic sepsis and one further patient developed grade III peripheralneurotoxicity that did not resolve within two months after chemotherapy hadbeen terminated. Overall objective response rate was 70%. The MTD forpaclitaxel was 185 mg/m² and AUC 6 for carboplatin,respectively. Secondary prophylaxis with G-CSF did not allow further doseescalation and therefore is not generally recommended.Conclusions: Paclitaxel 185 mg/m² given as three-hourinfusion followed by carboplatin AUC 6 is a feasible and safe regimen and canbe recommended for phase III trials. Observed response rates justify furtherevaluation of this combination. A randomized phase III trial comparing athree-hour infusion of paclitaxel 185 mg/m² combined witheither carboplatin AUC 6 or cisplatin 75 mg/m² as first-linechemotherapy of advanced ovarian cancer has recently been initiated by ourgroup.     

Phase I trial of carboplatin and weekly paclitaxel in patients with advanced non-small-cell lung cancer

OBJECTIVE: This study was designed to determine the maximum tolerated dose of paclitaxel administered weekly in combination with carboplatin and to assess its dose limiting toxicity and preliminary activity in patients with previously untreated, advanced non-small-cell lung cancer. METHODS: Carboplatin was administered at a fixed dose that maintained an area under the curve of 6. Paclitaxel was given over 1 h once a week for 3 weeks starting at 60 mg/m(2) and escalated in 10 mg/m(2) increments. RESULTS: Twenty-one patients were treated with six dose levels (60, 70, 80, 90, 100, 110 mg/m(2)) of paclitaxel. The dose limiting toxicity was infection and the maximum tolerated dose was 110 mg/m(2). Nine of 21 (42.9%) patients demonstrated a therapeutic response. CONCLUSION: Weekly paclitaxel and carboplatin were well tolerated. Based on our results, 100 mg/m(2) of paclitaxel for 3 weeks of a 4-week cycle, in combination with carboplatin, was recommended for a phase II study.     

Comparison of outcomes for elderly patients treated with weekly paclitaxel in combination with carboplatin versus the standard 3-weekly paclitaxel and carboplatin for advanced nonsmall cell lung cancer

BACKGROUND: The purpose of this study was to compare the outcomes between elderly (aged > or = 70 years) patients treated with paclitaxel on a weekly basis and with carboplatin (every 4 weeks) versus the standard 3-weekly regimen of carboplatin and paclitaxel for first-line therapy of advanced nonsmall cell lung cancer. METHODS: Of the 444 patients enrolled, 136 (31%) were aged > or = 70 years. Seventy-two patients were randomized to the weekly schedule (paclitaxel, 100 mg/m(2) weekly for 3 of 4 weeks; carboplatin, area under the curve [AUC] = 6 mg/mL.min on Day 1 every 4 weeks), and 64 patients were randomized to the standard schedule (paclitaxel, 225 mg/m(2); carboplatin, AUC = 6 mg/mL.min on Day 1 every 21 days). Patients with stable disease or objective response after 4 cycles of therapy were eligible for maintenance therapy with weekly paclitaxel (70 mg/m(2), 3 of 4 weeks). RESULTS: The response rate for elderly patients was 26% on the weekly regimen and 19% on the standard schedule. The median survival duration for the weekly and the standard schedules was 37 weeks and 31 weeks, respectively. The 1-year survival rates were similar at 31% and 33%. Grade 3 to 4 anemia was more common on the weekly schedule (16% vs 6%), whereas grade 3 neuropathy was less common (5.5% vs 9.5%). Nausea and emesis were also less frequent on the weekly schedule. CONCLUSIONS: Efficacy was similar between the weekly regimen and the standard regimen of carboplatin and paclitaxel for elderly patients with advanced NSCLC and may be advantageous based on its favorable tolerability profile.     

Phase II trial of a paclitaxel and carboplatin combination in Asian patients with metastatic nasopharyngeal carcinoma

Purpose: An earlier phase II trial of paclitaxel in patients with metastatic nasopharyngeal carcinoma (NPC) demonstrated a response rate of 22%. Hence we proceeded to study the combination of paclitaxel and carboplatin in these patients.Patients and methods: The 21-day regimen was as follows: i.v. paclitaxel 175 mg/m2 over three hours preceded by standard premedications, followed by i.v. carboplatin dosed at AUC of six infused over one hour. Only chemotherapy-naïve patients with histological diagnoses of undifferentiated carcinoma of the nasopharynx, systemic metastases and radiologically measurable lesions were eligible.Results: Thirty-two patients were accrued to this study. Twenty patients (62%) had at least two sites of metastasis. The main grade 3–4 toxicity was neutropenia (31%). Nine patients (28%) developed neutropenic sepsis, which caused the demise of one of them. Twenty-four patients (75%) responded to treatment, with one (3%) attaining a complete response. The median time to progression of disease was seven months and the median survival was 12 months. At one year, 52% of the patients were alive.Conclusions: The combination of paclitaxel and carboplatin is an active regimen in NPC. Its convenience of administration and good tolerability make it an attractive alternative regimen to consider for patients with metastatic disease.     

Final overall survival results of phase III GCIG CALYPSO trial of pegylated liposomal doxorubicin and carboplatin vs paclitaxel and carboplatin in platinum-sensitive ovarian cancer patients

Background:The CALYPSO phase III trial compared CD (carboplatin-pegylated liposomal doxorubicin (PLD)) with CP (carboplatin-paclitaxel) in patients with platinum-sensitive recurrent ovarian cancer (ROC). Overall survival (OS) data are now mature.Methods:Women with ROC relapsing >6 months after first- or second-line therapy were randomised to CD or CP for six cycles in this international, open-label, non-inferiority trial. The primary endpoint was progression-free survival. The OS analysis is presented here.Results:A total of 976 patients were randomised (467 to CD and 509 to CP). With a median follow-up of 49 months, no statistically significant difference was observed between arms in OS (hazard ratio=0.99 (95% confidence interval 0.85, 1.16); log-rank P=0.94). Median survival times were 30.7 months (CD) and 33.0 months (CP). No statistically significant difference in OS was observed between arms in predetermined subgroups according to age, body mass index, treatment-free interval, measurable disease, number of lines of prior chemotherapy, or performance status. Post-study cross-over was imbalanced between arms, with a greater proportion of patients randomised to CP receiving post-study PLD (68%) than patients randomised to CD receiving post-study paclitaxel (43%; P<0.001).Conclusion:Carboplatin-PLD led to delayed progression and similar OS compared with carboplatin-paclitaxel in platinum-sensitive ROC.     

A phase II study of weekly paclitaxel and carboplatin in previously untreated patients with advanced non-small-cell lung cancer

Purpose: Both paclitaxel (P) and carboplatin (C) have a significant activity in non-small cell lung cancer (NSCLC). Weekly administration of P is active, is dose intense, and has a favorable toxicity profile. To evaluate the efficacy and toxicity of weekly P and C in advanced-stage NSCLC, we initiated this phase II study in patients with advanced NSCLC (III B with pleural effusion and stage IV). Patients and Methods: Eligible patients were treated with paclitaxel 100 mg/m² intravenously (iv) over 1 h followed by carboplatin AUC 2 iv over 30 min. This treatment was administered weekly for 3 of every 4 wk until disease progression or intolerable toxicities. Results: Of the 30 patients enrolled in the study, one patient did not meet the eligibility criteria. Of the remaining 29 patients, 6 did not complete at least two cycles of treatment and hence were not assessable for response. The overall response rate was 43.5% (10/23) (all partial responses). An additional 43.5% had stable disease. The median time to progression was 162 d and the median duration of response was 169 d. Overall survival at 1 yr on intent-to-treat analyses was 44% and median survival was 10.8 mo. We observed the following grade 3/4 toxicities: hypersensitivity to paclitaxel (13%), hypersensitivity to carboplatin (3%), neutropenia (31%), thrombocytopenia (7%); 31% experienced grade 1 neuropathy and 17% experienced grade 2 neuropathy. Conclusions: We conclude that weekly paclitaxel and carboplatin is active and very well tolerated in patients with advanced NSCLC.     

Phase I/II study of cisplatin combined with weekly paclitaxel in patients with advanced non-small-cell lung cancer

To determine the maximum-tolerated dose (MTD) and the recommended dose (RD) of paclitaxel administered weekly with a fixed dose of cisplatin, and to assess the toxicity and activity of this combination, we conducted a phase I/II trial in patients with advanced non-small-cell lung cancer (NSCLC). In this study, patients with stage IIIB/IV NSCLC were eligible. Paclitaxel, at a starting dose of 40 mg x m(-2) week(-1) on days 1, 8, and 15, was combined with a fixed dose of cisplatin 80 mg x m(-2) on day 1. Chemotherapy was given in a 4-week cycle. In this phase I/II study, 38 patients were enrolled. Dose-limiting toxicities (DLT) were neutropenia, fatigue, and omission of treatment due to leucopenia, thrombocytopenia, or febrile neutropenia. The MTD and RD were estimated to be 70 mg x m(-2). Of the 37 assessable patients, 23 had a partial response and one had a complete response. Overall response rate was 62.1% (95% confidence interval (CI): 46.5-77.7%). The progression-free survival, the median survival time, and the 1-year survival rate were 5.5 months, 13.7 months, and 56.9%, respectively. This regimen is tolerable and very active against advanced NSCLC, and its efficacy should be confirmed in a phase III study.     

Weekly dose-dense paclitaxel and carboplatin in recurrent ovarian carcinoma: A phase II trial

PurposeThe aim of this study was to investigate efficacy and toxicity of the dose-dense weekly paclitaxel (T) and carboplatin (C) in the management of platinum-resistant/sensitive recurrent epithelial ovarian cancer (EOC) previously treated with 3 weekly paclitaxel/carboplatin.MethodsThirty two patients with recurrent EOC who had received 3 weekly TC before were enrolled. Nine patients relapsed within 6 months (platinum-resistant), 13 patients relapsed after 12 months (platinum-sensitive) and in 10 patients recurrence occurred between 6 and 12 months (intermediate platinum-sensitive). Weekly (T) at a dose of 80 mg/m², followed by weekly (C) AUC 2 on day 1, 8, and 15 of a 28-day cycle for 6 planned cycles were administrated. End-points were overall response rate (ORR), progression free survival (PFS), overall survival (OS) and toxicity.ResultsThe ORR was 62.5%. For the platinum-resistant, intermediate platinum-sensitive and platinum-sensitive patients the ORR was 44.4% (4/9), 60% (6/10) and 76.9% (10/13), respectively, and 1 (11.1%), 2 (20%) and 5 (38.46%) patients, respectively had CR. PFS was 9.1 months (6.13, 9.1 and 12.17 months, for the 3 groups, respectively) (P < 0.001). OS was 14 months (9.17, 15.2, and 19.23 months, for the 3 groups, respectively) (P < 0.001). Treatment-related adverse events were manageable with only 1 patient (3.1%) suffering from grade 4 neutropenia. Grade 3 hematological and non-hematological toxicities were neutropenia in 8 (25%), and peripheral neuropathy in 4 (12.5%) patients, respectively.ConclusionWeekly TC is active and well-tolerated in platinum-resistant and platinum-sensitive patients with recurrent EOC previously treated with TC given every 3 weeks.     

A phase II feasibility study of carboplatin followed by sequential weekly paclitaxel and gemcitabine as first-line treatment for ovarian cancer

A total of 53 women with chemotherapy-na?ve stage Ic-IV ovarian cancer were treated with four cycles of carboplatin area under the curve 7 every 3 weeks, followed by four cycles of paclitaxel 70 mg m(-2) (days 1, 8, and 15) and gemcitabine 1000 mg m(-2) (days 1 and 8) every 3 weeks. In all, 37 (70%) had stage III/IV disease, with 22 (42%) having tumour >2 cm; 38 patients (72%) completed all planned treatment; 27 of the 32 (84%) patients with radiologically evaluable disease had partial or complete responses; and 30 of the 39 patients (77%) with elevated cancer antigen (CA) 125 had a greater than 75% fall in this value. At a median follow-up of 28 months, 31 patients had relapsed with a median progression-free survival of 19.5 months. In total, 79% of patients were alive at 2 years. Common Toxicity Criteria grade 3/4 haematological toxicity, predominantly neutropenia, was seen in 57% of the patients. A certain degree of pulmonary toxicity was observed; eight patients had symptomatic breathlessness, +/- decreased diffusing capacity of the lung for carbon monoxide, and interstitial chest X-ray changes during the weekly phase. In all cases, this toxicity was reversible. No significant neurotoxicity was seen. This regimen is generally well tolerated with encouraging efficacy. However, the observation of pulmonary toxicity, potentially a feature of the weekly taxane-gemcitabine regimen, was of some concern. Alternative schedules, including 3-weekly taxanes, are currently being evaluated.     

紫杉醇脂质体联合卡铂治疗晚期卵巢上皮癌的临床分析

目的研究紫杉醇脂质体联合卡铂方案化疗治疗晚期卵巢上皮癌的临床疗效和毒副作用。方法对经减瘤术后病理组织学确诊的Ⅲ一Ⅳ卵巢上皮癌患者26例,采用紫杉醇脂质体联合卡铂方案化疗,其中紫杉醇脂质体130～175mg／m^2第1天静脉滴注;卡铂300mg／m^2第2天静脉滴注,每21天为1个周期,每2个周期评价1次疗效。结果26例患者完全可以评价疗效,其中完全缓解7例,部分缓解11例,稳定6例,进展3例,总有效率为69．23％,其中Ⅲ期有效率为72．22％,Ⅳ期有效率为62．50％。中位疾病进展时间（MTYP）10个月（5～13个月）,无复发生存期5个月。毒副作用主要为骨髓抑制和胃肠道反应。结论紫杉醇脂质体联合卡铂方案治疗晚期卵巢上皮癌近期疗效好,毒副作用可以耐受,值得临床推广使用。     

Phase I/II investigation of paclitaxel, ifosfamide and carboplatin for advanced non-small-cell lung cancer.

BACKGROUND: The aim of this study was to evaluate feasibility and tolerability of the three-drug combination of paclitaxel, ifosfamide and carboplatin (TIC) in patients with advanced non-small-cell lung cancer. The specific objectives of the study were: (i) to define the dose-limiting toxicities (DLTs) and the maximum-tolerated dose of ifosfamide administered as part of the combination; and (ii) to determine the overall response rate and overall survival of patients treated with this regimen. PATIENTS AND METHODS: Patients with untreated, stage IIIB (pleural effusion) or stage IV non-small-cell lung cancer were enrolled in one of three cohorts. Patients received paclitaxel 200 mg/m(2) as a 1-h infusion on day 1 with carboplatin at an area under the concentration-time curve (AUC) of 6 mg.min/ml on day 2. For dose level I, ifosfamide was administered at a dose of 2 g/m(2) on days 1 and 2. For dose levels II and III, the dose of ifosfamide was decreased to 1.5 g/m(2) on days 1 and 2 and the dose of carboplatin was decreased to AUC 5 mg.ml/min. Therapy for dose levels I and III included filgrastim support (5 micro g/kg/day), which was initiated on day 3 and continued until after day 11 or until an absolute neutrophil count >10 000/ micro l. Treatment cycles were repeated every 21 days. Once the phase II dose was established, a full cohort of patients received therapy at this dose level to examine further the regimen's activity and tolerability. RESULTS: Neutropenia was the DLT encountered for dose levels I and II. No DLT was encountered in the initial six patients treated at dose level III, and therefore this dose level was declared the recommended phase II dose. A total of 49 patients were treated at the recommended phase II dose. The predominant non-hematological toxicity encountered with this triplet regimen was cumulative peripheral neuropathy. Of the 65 eligible patients enrolled in this study, 17 (26%) responded. There were 15 patients with partial responses (23%), two with regression, and 26 with stabilization of disease (40%). Median progression-free and overall survival were 4.8 and 9.4 months, respectively. CONCLUSIONS: The combination TIC is well-tolerated. This triplet regimen produced response and survival rates in advanced non-small-cell lung cancer similar to those of other current combination chemotherapy regimens.     

Phase I evaluation of continuous 5-fluorouracil infusion followed by weekly paclitaxel in patients with advanced or recurrent gastric cancer

OBJECTIVE: We conducted a phase I trial of escalating doses of weekly paclitaxel (Taxol) in combination with a fixed systemic administration of 5-fluorouracil (5-FU) in patients with advanced or metastatic gastric cancer. METHODS: Patients with advanced or recurrent gastric cancer were treated with escalating doses of weekly paclitaxel as a 60 min intravenous (i.v.) infusion, along with a fixed dose of continuous 5-FU infused over 5 days. Plasma sampling was performed to characterize the pharmacokinetics and pharmacodynamics of paclitaxel. RESULTS: Eighteen patients received combination therapy at four dose levels of weekly Taxol, ranging from 60 to 90 mg/m2/week. Dose-limiting toxicities > grade 3 were observed at the 90 mg/m2/week dose level. Toxicities included anemia, neutropenia, thrombocytopenia, nausea and alopecia. Two episodes of grade 4 neutropenia occurred in two of the three patients receiving this dose. At each dose level, pharmacological studies documented the persistence of significant serum paclitaxel levels over 24 h after drug administration. The maximum tolerated dose (MTD) for this regimen was 90 mg/m2/week of paclitaxel for 3 weeks plus 600 mg/m2/day of continuous 5-FU for 5 days. CONCLUSIONS: The combination of weekly paclitaxel and 5-FU demonstrated an acceptable toxicity profile and feasible pharmacokinetic results suggesting its practical applicability. Based on these findings, the recommended dose and schedule for phase II study of combination chemotherapy is paclitaxel 80 mg/m2/week x 3 over 4 weeks, and continuous 5-FU 600 mg/m2/day x 5 days every 4 weeks.     

Phase II study of paclitaxel and carboplatin in advanced gastric cancer previously treated with 5-fluorouracil and platinum

BACKGROUND: The combination of paclitaxel and carboplatin has been used to treat patients with many types of tumor, including gastric cancer. We evaluated the efficacy and safety of this combination in advanced gastric cancer patients previously treated with 5-fluorouracil and platinum. METHODS: Patients who had pathologically been proven to have measurable lesions were treated with paclitaxel (200 mg/m(2) for 3 h) and carboplatin [area under the concentration-time curve (AUC = 6)] on day 1 and in 21 day cycles. RESULTS: A partial response was achieved in 10 of 45 patients [22%, 95% confidence interval (CI), 10-34]. Of the 32 patients previously treated with cisplatin, four (13%) achieved partial response, whereas, of the 13 patients previously treated with heptaplatin, six (46%) achieved partial response. In all patients, the median time to progression was 14 weeks (95% CI, 10-18), and the median overall survival was 32 weeks (95% CI, 26-38). The most common grade 3/4 adverse events were neutropenia (40% of patients) and neuropathy (2.2%). Two patients developed neutropenic fever. However, there were no treatment-related deaths. CONCLUSIONS: Combination chemotherapy with paclitaxel and carboplatin is feasible in patients with advanced gastric cancer who were previously treated with 5-fluorouracil and platinum.     

甘氨双唑钠(CMNa)联合紫杉醇卡铂化疗对中晚期卵巢癌术后CA125升高的影响

Objective:To investigate the effects of CMNa combined with paclitaxel and carboplatin on elevated CA125 levels in post-operation advanced ovarian cancer patients.Methods:The effects of CMNa combined with paclitaxel and carboplatin on elevated CA125 levels in 25 post-operation advanced ovarian cancer patients were retrospectively analyzed and compared with those in 20 control cases.Results:After 1 cycle of chemotherapy,CA125 levels had decreasing trend compared with control,but had no statistical significance.While after two cycles of chemotherapy,CA125 levels decreased more rapidly compared with those in control.Side effects in two groups were alike.Conclusion:CMNa combined with paclitaxel and carboplatine has a stronger effect on the decrease of elevated CA125 levels than paclitaxel and carboplatin have in the treatment of post-operation advanced ovarian cancer,which indicates that CMNa has chemo-sensitizing effects on chemotherapy of paclitaxel and carboplatin.     

A randomized phase II trial comparing every 3-weeks carboplatin/paclitaxel with every 3-weeks carboplatin and weekly paclitaxel in advanced non-small cell lung cancer.

BACKGROUND: The optimal schedule of taxane administration has been an area of active interest in several recent clinical trials. METHODS: To address a pure schedule question, we randomized 161 patients with advanced stage IIIB or IV non-small-cell lung cancer (NSCLC) to either paclitaxel 225 mg/m2 every 3 weeks x 4 cycles or 75 mg/m2/week x 12 (cumulative dose on each arm = 900 mg/m2). Both arms received concurrent carboplatin AUC 6 every 3 weeks x 4 cycles. RESULTS: The two arms were well-balanced in terms of known prognostic factors. The overall response rate and survival outcomes were similar on the two arms. There was significantly more grade 3/4 thrombocytopenia and grade 2-4 anemia on the weekly arm but less severe myalgias/arthralgias and alopecia. No difference in the rates of peripheral neuropathy was observed; however, patients on the every 3 weeks arm reported significantly more taxane therapy-related side-effects on the functional assessment of cancer therapy taxane subscale. CONCLUSIONS: This randomized trial exploring schedule-related issues with carboplatin/paclitaxel confirms the versatility of this regimen.     

Phase I dose escalation study of topotecan combined with alternating schedules of paclitaxel and carboplatin in advanced solid tumors

Background:Combining topotecan with other cytotoxics has been problematic due to marrow suppression. A phase I trial was initiated to identify the optimal sequence and maximum-tolerated dose of topotecan in combination with paclitaxel and carboplatin. Patients and methods:Patients with advanced cancer and performance status ECOG 2. The starting dose was paclitaxel 175 mg/m² day 1, carboplatin AUC 6.0 day 1, and topotecan 0.5 mg/m² daily day 1–5 (early sequence). The next course of paclitaxel and carboplatin administration was delayed to day 5 (late sequence). Treatment was repeated every three weeks. After determining maximum-tolerated dose without cytokines, granulocyte colony-stimulating factor (G-CSF) was added and further dose escalation was pursued. Results:Fifty-one patients were entered; men : women ratio 30 : 21. Dose-limiting toxicity (DLT) for the early sequence was neutropenia at doses paclitaxel mg/m²/carboplatin AUC 5/topotecan mg/m² (PCT) 175/5/0.75 for four to five days. DLT for the late sequence was neutropenia at PCT doses of 175/5/1.0 for four days. G-CSF 5 µg/kg subcutaneously starting day 6 permitted further topotecan dose escalation. After adding G-CSF, late sequence DLT was neutropenia at doses 175/5/1.25 for four days. Forty-six patients were evaluable for response and of those, there were thirteen partial responses. Conclusions:The late sequence resulted in less toxicity and was better tolerated. The early sequence maximum-tolerated dose (MTD) was 175/6/0.5 for five days. The late sequence MTD was PCT 175/5/0.75 for five days. The late sequence MTD with G-CSF was 175/5/1.0 for four days. The recommended phase II PCT dose is the late sequence 175/5/1.0 for four days with G-CSF.