Phase II randomized multicenter study evaluating a treatment regimen alternating docetaxel and cisplatin-vinorelbine with a cisplatin-vinorelbine control group in patients with stage IV non-small-cell lung cancer: GFPC 97.01 study.

BACKGROUND: The potential absence of cross-resistance between cisplatin and docetaxel in non-small-cell lung cancer (NSCLC) suggests that alternating regimens of cisplatin-based chemotherapy and docetaxel might increase the activity of chemotherapy in stage IV NSCLC. PATIENTS AND METHODS: Randomized, multicenter, non-comparative phase II study in patients with stage IV NSCLC (Eastern Cooperative Oncology Group performance status of 0-2). Patients randomized to alternating treatment group (A) received docetaxel 100 mg/m2 on days (D) 1 and 43 alternating with cisplatin 100 mg/m2 on D22 and vinorelbine 30 mg/m2 on D22, D29 and D36. Those randomized to the control group (B) received cisplatin 80 mg/m2 on D1, D22 and D43 and vinorelbine 30 mg/m2 once a week from D1 to D57. Treatment was continued for a further 6 weeks in the event of objective response or stabilization. RESULTS: Seventy patients were enrolled (group A: 38, group B: 32). More premature treatment discontinuations due to toxicity were observed in group A (median number of cycles: 3) than in group B (median number of cycles: 5). The intention-to-treat objective response rate was 10.8% [95% confidence interval (CI) 0.8% to 20.8%] in group A compared with 25% (95% CI 10% to 40%) in group B, the median time to treatment failure being 10.2 weeks and 17.3 weeks, respectively. The median survival and 1-year survival were 29.1 weeks and 39% in group A compared with 41.6 weeks and 42% in group B. Febrile neutropenia occurred in 5.9 and 4.9% of the cycles in group A and group B, respectively. Non-hematological toxicity was moderate in the two groups. CONCLUSIONS: The addition of docetaxel alternating with cisplatin-vinorelbine did not enhance the activity of this combination. The development of sequential regimens might be a more promising way of exploiting the absence of cross-resistance between these two drugs.

Dose-finding, pharmacokinetic and phase II study of docetaxel in combination with gemcitabine in patients with inoperable non-small cell lung cancer.

BACKGROUND: The good efficacy-toxicity ratio of both docetaxel and gemcitabine in non-small cell lung cancer (NSCLC) stimulates the investigation of the combination of these drugs as a first line chemotherapy. This two-step study firstly aimed at determining the maximum tolerated and recommended doses of docetaxel given every 3 weeks in combination with a fixed dose of gemcitabine; the phase I study paid particular attention to pharmacokinetics. Afterwards, the safety and efficacy of the recommended dose was carefully assessed in the phase II-step. METHODS: The following range of docetaxel dosages were tested in the phase I study; 60, 75, 85, and 100 mg m(-2) given on day 8 in combination with gemcitabine 1000 mg m(-2) delivered on days 1 and 8 of a 3-week cycle. Haematopoietic growth factors were not allowed. The treatment was delivered on an outpatient basis. Main eligibility criteria consisted of stage III b or IV histologically proven NSCLC, Eastern Co-operative Oncology Group (ECOG) performance status PS < or =2, age < or =70 years, measurable disease, adequate blood counts, chemistry, and no symptomatic brain metastasis. RESULTS: Four centres enrolled 49 patients (eight having been pre-treated); 16 in phase I and 33 in phase II. The maximal tolerated dose was almost reached at the last dose level (i.e. docetaxel, 100 mg m(-2)). Consequently, we considered the 85 mg m(-2) level as the recommended dose. There was a positive relationship of the docetaxel dose to the area under the curve of this drug. Toxicity was assessable in all patients. Among the 200 cycles delivered, 192 were assessable for this feature. Main toxicity was grade 3-4 neutropenia affecting 23 patients (47% of the population; 23% of the cycles). Six febrile episodes were recorded leading to two treatment-related deaths. Another patient died from congestive cardiac failure. In addition, six patients experienced interstitial pneumonitis, (one half considered as severe), two of them having received the recommended dose. All patients recovered from this toxicity after corticosteroids. Fourteen patients out of the whole population (29%; 95% CI [17-43], including ten patients receiving the recommended dose), achieved an objective response. Median follow-up was 14 months (range, 0.3-29.4). Median survival was 11.2 months (95% CI [8.3-13.2]), and the 1-year survival rate was 45%. CONCLUSION: Gemcitabine, 1000 mg m(-2) days 1 and 8 in combination with docetaxel, 85 mg m(-2), day 8, given every 3 weeks could be considered as an active regimen with manageable toxicities in locally advanced or metastatic NSCLC. This study deserves further comparisons with classical platinum-based regimens.

[Phase II study of docetaxel in inoperable advanced non small cell lung cancer]. / Etude de phase II: docétaxel dans les cancers bronchopulmonaires non à petites cellules inopérables.

The purpose is to determine the response to, and toxicity of docetaxel (Taxotère) in patients with inoperable non small cell lung cancer (NSCLC), previously untreated. Seventy patients with stage IIIB or IV NSCLC were treated by 100 mg/m2/ 3 weeks of docetaxel until tumor progression or severe toxicity. Premedication with diosmine and prednisolone was given in all patients: 66/70 were eligible and 55/70 were assessable for antitumoral activity. Median age: 63 years, WHO performans status 0-1: 83%, stage IV: 96%. For eligible patients, 17/66 (26%) achieved an objective response: 1 complete response and 16 partial response (IC 95% = 15-36). With a median follow-up of 23.4 months (range 14.9-28.7), for evaluable patients, the median response duration was 8 months, the median time to progression 4 months, and the median survival time 10 months. The median number of administered cycles is 5 (range 1-12). The estimate one year survival rate was 47%. Seventy-six patients presented neutropenia (grade 3-4); febrile neutropenia was observed in 7% of cycles. Non haematological toxicities are: fluid retention related to docetaxel (2.9%), diarrhea (6%), nausea-vomiting (4%), asthenia (3%), nail changes (6%). Docetaxel (Taxotère) administered at 100 mg/m2/3 weeks has relevant clinical activity in previously untreated NSCLC with a acceptable toxicity.

[Efficacy of docetaxel in non-small cell lung cancer patients previously treated with platinum-containing chemotherapy. French Group of Pneumo-Cancerology]. / Efficacité du docétaxel dans les cancers bronchopulmonaires non à petites cellules antérieurement traités par une chimiothérapie comportant des sels de platine. Groupe Français de Pneumo-Cancérologie.

PURPOSE: Determine the response to, and toxicity of docetaxel (Taxotere) in patients (pts) with inoperable non-small-cell lung cancer (NSCLC) previously treated with platinum-containing chemotherapy. PATIENTS AND METHODS: Twenty-seven patients with stage IIIB or IV NSCLC, having received one platinum-containing regimen were treated with 100 mg/m2/3 weeks of docetaxel until tumor progression or severe toxicity. Premedication with prednisolone and diosmin was given in all patients. Antitumoral activity was assessable in 21/27 pts. Median age: 52 years; WHO performance status 0-1: 77% pts, stage IV disease: 63% pts. RESULTS: 6/21 eligible pts (24%) achieved a partial response to treatment [C.I 95%: 5.6-42]. Median time to progression: 2.9 months, median survival: 8.5 months with a median follow-up of 23.7 months (range: 13.5-27). Hematologic toxicity: grade 3-4 neutropenia: 75% pts, febrile neutropenia: 11% cycles. Non hematologic toxicities: fluid retention, rash, alopecia, sensory neuropathy, asthenia, and nail changes. CONCLUSION: Docetaxel (Taxotere) administered at 100 mg/m2/3 weeks has relevant clinical activity against platinum treated NSCLC pts. Neutropenia is the main toxicity.