Docetaxel as salvage therapy in advanced gastric cancer: a phase II study of the Gruppo Oncologico Italia Meridionale (G.O.I.M.).

BACKGROUND: Docetaxel (DCT), a semisynthetic taxoid, has demonstrated cytotoxic activity against gastric cancer in early phase II studies producing an overall response rate of 17-24%. The Gruppo Oncologico Italia Meridionale (G.O.I.M.) started a confirmatory multicenter phase II trial to evaluate the clinical activity and toxicity of single agent TXT in the treatment of advanced gastric cancer patients who had failed a first-line chemotherapy. MATERIALS AND METHODS: Thirty patients with advanced gastric carcinoma refractory to first-line ECF or PELF chemotherapy were treated with DCT administered at the dosage of 100 mg/mq given as a 1-hour i.v. infusion every three weeks. All patients received a premedication with dexamethasone 8 mg i.v. 12 hours and 1 hour before, and 12 hours after DCT administration. Granulocyte colony stimulating factor was employed in case of febrile neutropenia as needed. The first evaluation of disease status was planned after three cycles. RESULTS: We observed 5 partial responses without any complete response for an overall response rate of 17% (95% CI = 6-36%, intent-to-treat analysis). Nine patients showed stable disease and 14 patients progressed. The duration of objective partial responses were 5, 6, 6, 9 and 12 months, respectively. The median overall survival was 6 months and the 1-year survival rate was 20.6%. No chemotherapy-related toxic death was observed. Haematological grade 3-4 side-effects were respectively: anemia (7%), leucopenia (7%) and neutropenia (18%); in 13 patients (45%) G-CSF was employed to avoid severe leukopenia. CONCLUSION: This multinstitutional single-step phase II study confirms that single-agent docetaxel is active in advanced gastric cancer progressing after first-line chemotherapy. The most frequent toxicity is neutropenia, which may be managed by G-CSF and/or dose adjustments. Docetaxel is therefore worthy of further study in combination with other active drugs.

Escalating doses of paclitaxel and epirubicin in combination with cisplatin in advanced ovarian epithelial carcinoma: a phase I-II study.

Our objective was to identify a new active three-drug combination regimen consisting of paclitaxel (PTX), epirubicin (EPI) and cisplatin as first-line line chemotherapy for advanced ovarian carcinoma. A phase I study was carried out to evaluate the dose-limiting toxicity (DLT) and the maximally tolerated dose (MTD) of PXT and EPI in combination with a fixed dose of cisplatin every 4 weeks. Side-effects were recorded according to the NCI Common Toxicity Criteria. Patients were treated in cohorts of three with fixed-dose cisplatin 80 mg/m2 and EPI 80-->100 mg/m2 and PXT 100-->160 mg/m2 until DLT was reached. Once MTD was identified, a single-step phase II study was therefore carried out to test the clinical activity and panel of toxicity of such regimen. Objective responses were recorded according to the WHO criteria. Time to progression and overall survival (OS) were secondary endpoints. The DLT was myelosuppression and, in more detail, febrile neutropenia, which occurred at the fifth dose level (PTX 140 mg/m2, EPI 100 mg/m2 and cisplatin 80 mg/m2) in two out of three patients. Other side-effects were grade 3 mucositis in two out of three patients and grade 3 anemia in one case. The combination of cisplatin 80 mg/m2 plus EPI 80 mg/m2 and PCT 140 mg/m2 every 4 weeks was considered as the MTD. In the phase II study a complete response was observed in six patients (33%) and a partial response in nine cases (50%) for an overall response rate of 83% [95% confidence limits (CL) 59-96%]. Median time to progression of patients with measurable disease was 16.4 months. Median OS was not reached after a follow-up of 42 months. This study demonstrated that PTX and EPI can be safely administered in combination with cisplatin to fit patients with advanced epithelial ovarian carcinoma. The three-drug regimen of cisplatin 80 mg/m2, EPI 80 mg/m2 and PTX 140 mg/m2 every 4 weeks is very active, at least in terms of objective response rate. This level of activity overlaps with the 95% CL of the activity of cisplatin alone; however, it does encourage future trials of the combination.

Vinorelbine plus cisplatin versus cisplatin plus vindesine and mitomycin C in stage IIIB-IV non-small cell lung carcinoma: a prospective randomized study.

PURPOSE: To compare a regimen of vinorelbine and cisplatin (VC) to the combination of mitomycin, vindesine, and cisplatin (MVP) in patients with stage IIIB or stage IV non-small cell lung cancer (NSCLC). The main endpoits were analysis of objective response rates, toxicity, time to progression, and overall survival. PATIENTS AND METHODS: 247 eligible patients were randomized to receive (a) vinorelbine 25 mg/m(2) intravenous bolus on days 1 and 8 plus cisplatin 100 mg/m(2) on day 1 every 4 weeks, or (b) mitomycin c 8 mg/m(2) i.v. on day 1, vindesine 3 mg/m(2) i.v. on days 1, 8, 15 and 22, plus cisplatin 100 mg/m(2) on day 1 every 4 weeks. In subsequent cycles vindesine was given every other week. For both treatments a maximum of six cycles was planned. Patients with performance status 0-2 according to the ECOG scale were enrolled. Response and toxicity were evaluated according to the WHO criteria. Analysis of clinical efficacy was performed according to an intent-to-treat analysis. RESULTS: No statistically significant differences in clinical efficacy were observed between the two chemotherapy regimens. The overall objective response rates were 39% (95% CL, 31-49%) in the VC arm and 42% (95% CL, 33-51%) in the MVP arm (P=0.13). Median time to progression was 4.2 and 4.5 months for the MVP arm and the VC arm, respectively. Median overall survival was 7 months in the VC arm and 8 months in the MVP one (log-rank test, P=0.898). These differences were not statistically significant. However, leukopenia and thrombocytopenia were significantly higher in the MVP arm than in the VC (P=0.0001; P=0.0002). Grade 3 alopecia was more frequent in the MVP arm than in the VC one (P<0.001), which was associated with higher rate of phlebitis (P=0.037). CONCLUSION: Data achieved in this study suggest that the vinorelbine-cisplatin doublet is similar to the three-drug MVP regimen in term of overall response rate, time to progressive disease, and overall survival. However, hematological toxicity and alopecia are more frequent and severe in the MVP regimen which therefore appears to be less tolerable than the VC regimen. The combination of vinorelbine and cisplatin may be considered as a reference treatment for future studies on the treatment of advanced NSCLC.