First-line treatment of advanced nonsmall cell lung carcinoma with docetaxel and vinorelbine.

BACKGROUND: Docetaxel and vinorelbine are active agents in the treatment of nonsmall cell lung carcinoma (NSCLC). The efficacy and toxicity of this combination was evaluated in a Phase II study in patients with advanced NSCLC. METHODS: Forty-six chemotherapy-naive patients (44 men and 2 women with a median age of 64 years) with NSCLC (11 with Stage IIIB and 35 with Stage IV disease) were entered into the study; the World Health Organization (WHO) performance status was 0, 1, and 2 in 32, 11, and 3 patients, respectively. Patients received vinorelbine (25 mg/m2) on Day 1 and docetaxel (100 mg/m2) on Day 2 in cycles repeated every 3 weeks. Granulocyte-colony stimulating factor was given to all patients from Day 3 to Day 10. RESULTS: One hundred and seventy-seven courses of chemotherapy were administered. Adverse events included WHO Grade 4 neutropenia (15 patients), Grade 3/4 thrombocytopenia (3 patients), Grade 3 anemia (2 patients), Grade 2 and 3 neurotoxicity (7 patients and 1 patient, respectively), and Grade 3 fatigue (2 patients). Twenty patients (43%) required hospitalization: 11 (24%) for neutropenic fever (2 deaths from sepsis), and 9 (20%) for nonneutropenic pulmonary infections (2 deaths from cardiopulmonary insufficiency). The median overall survival was 5 months and the 1-year survival was 24%. Four complete responses (9.8%) and 11 partial responses (26.8%) (overall response rate of 36.6%; 95% confidence interval, 21.8-51.3%) were documented in 41 evaluable patients (intent-to-treat: 32.6%). Stable and progressive disease occurred in 13 patients each (31.7%). The median duration of response was 5 months and the median time to progression was 3 months (6 months for the responders). CONCLUSIONS: This schedule of docetaxel and vinorelbine combination is effective but its relatively high incidence of complicated neutropenia precludes its general use in patients with advanced NSCLC.

Concurrent platinum and docetaxel chemotherapy and external radical radiotherapy in patients with invasive transitional cell bladder carcinoma. A preliminary report of tolerance and local control.

PURPOSE: The present study aims to evaluate the feasibility, toxicity, and efficacy of concurrent chemotherapy with cisplatinum and docetaxel, and external radical radiotherapy for transitional cell carcinoma of urinary bladder. MATERIALS AND METHODS: 42 patients (34 men, 8 females) with invasive bladder carcinoma (clinical stages T1-4) were treated after transurethral biopsy with chemotherapy and concomitant external radiotherapy. Chemotherapy consisting of cisplatin infusion (30 mg/m2) and Docetaxel (40 mg/m2) was given twice a week simultaneously with-irradiation during the whole treatment period (6-8 weeks) as follows: Cisplatin (D1,D8,D15,D22, D25,D36,D43,D50) and Docetaxel (D4, D11, D18, D25, D32, D39, D46, D53). An external irradiation scheme 1.8 to 2.0 Gy per fraction, 5 days a week was used up to 68-74 Gy (6MeV photons) total tumor dose. RESULTS: All but S patients completed the planned chemoradiation protocol. The complete response rate (CR-rate) assessed at 3 months after completion of combined treatment was 100%, 63.6%, 46.15% and 95% for clinical stage (c) cT1 (9/9), cT2 (7/11), cT3 (6/13) and cT4 (1/4) cases respectively. None of 9 patients with T1 tumors had any local failure at 36.1 months mean follow-up time. In total, 9 of 37 patients (24.32%) relapsed locally and/or distantly and were followed for 25.04 months (mean time), 50% of the relapses occurred at a mean time of 7.25 months. The mortality rate was 10.81% (4/37). All these patients died with a mean time of 11 months. 32 cases remain alive 19-46 months after treatment; 27 of those are with no evidence of disease with a mean follow-up time of 32.24 months. In total, there was a 78.50% (30/37) and a 75.67%, (28/37) rate of overall survival and pelvic control respectively at 25.04 months mean follow-up time. Chemotherapy was discontinued in 2 cases due to acute gastrointestinal toxicity and in 3 more, due to patient compliance. There was 1 toxic death 2 months after treatment completion due to ureteral obstruction and impaired renal function. The acute toxicity was estimated as moderate to severe and caused the interruption of treatment for 5 to 10 days in 8 of 37 patients (21.62%). Myelotoxicity appeared in 22/37 patients but febrile grade III and IV neutropenia was observed in 3 patients (8.10%) and thrombocytopenia (Grade I-III) in 8 (21.62%). Concerning late effects a sigmoid stricture, a transient small bowel obstruction, 4 patients with contracted bladder and 1 case with renal failure were found. Grade I to III hypersensitivity reactions appeared in 8/37 patients (21.62%) while stomatitis (grade I-II) and grade II skin toxicity appeared in 3 and 4 patients respectively. These and other symptoms (Grade I to II peripheral edema, transient myalgias and arthralgias in 7/37 cases), paresthesias or numbness (3/37) and peripheral motor dysfunction (1/37) were responsible for early reduction of docetaxel dose from 40 mg/m2 to 20 mg/m2. CONCLUSION: This preliminary analysis suggest that the radiosensitizing effect of cisplatin and docetaxel to megavoltage irradiation yielded a high CR-rate in transitional cell bladder carcinoma patients with medium to severe early and late side effects. The value of such a combined treatment as far as the tumor eradication is concerned requires further evaluation, because of the small number of patients, the short follow-up, and the absence of other studies using docetaxel as a radiosensitizer in urothelial cell cancer.