A phase II trial of erlotinib as maintenance treatment after concurrent chemoradiotherapy in stage III non-small-cell lung cancer (NSCLC): a Galician Lung Cancer Group (GGCP) study.

PURPOSE: This single arm, phase II study aims to evaluate the role of epidermal growth factor receptor-tyrosine-kinase inhibitor erlotinib as maintenance therapy following concurrent chemoradiotherapy (cCRT) in unresectable locally advanced non-small-cell lung cancer (NSCLC). METHODS: Patients with unresectable stage IIIA o dry IIIB NSCLC with no evidence of tumor progression after receiving a standard cCRT regimen with curative intent were included. Oral erlotinib 150 mg/day was administered within 4-6 weeks after the end of the cCRT for a maximum of 6 months if no disease progression or intolerable toxicity occurred. Primary end point was the progression-free rate (PFR) at 6 months. Secondary end points included time to progression (TTP) and overall survival (OS). RESULTS: Sixty-six patients were enrolled and received maintenance treatment with erlotinib [average: 4.5 months (95 % CI 4.0-5.0)]. PFR at 6 months was 63.5 % (41/66). With a median follow-up of 22.7 months (95 % CI 13.5-37.1), the median TTP was 9.9 months (95 % CI 6.2-12.1), and the median OS was 24.0 months (95 % CI 17.3-48.6). Most common adverse events (AEs) related to erlotinib were rash (78.8 %; 16.7 % grade 3), diarrhea (28.8 %; 1.5 % grade 3), fatigue (15.2 %; 1.5 % grade 3), anorexia (7.6 %; 1.5 % grade 3) and vomiting (4.6 %; none grade 3). Five patients (7.6 %) were withdrawn due to AEs. CONCLUSIONS: Erlotinib as maintenance therapy is an active treatment after cCRT in unselected patients with stage III NSCLC, reaching a 6-month PFR of 63.5 % and a median OS of 24 months. The safety profile of maintenance erlotinib was as expected and manageable.

A phase II randomized trial of gemcitabine-docetaxel versus gemcitabine-cisplatin in patients with advanced non-small cell lung carcinoma.

PURPOSE: To test efficacy and tolerability of non-platinum regimens for advanced non-small-cell lung cancer (NSCLC). METHODS: Chemonaive patients with measurable stage IIIB/IV NSCLC treated with gemcitabine and cisplatin (GC), or gemcitabine and docetaxel (GD), maximumsix cycles in a phase IIB trial. RESULTS: A total of 108 patients were randomized. Response rates (GC vs. GD, respectively): complete 3.6/2.0%, Partial 30.9/38.0%. Median Overall Survival (OS): 8.9 months in both groups (P = 0.53); and median time to progression (TTP): 6.2/5.5 months respectively (P = 0.61). Toxicities included (GC vs. GD, respectively): grade 3-4 neutropenia 49.1/41.2%; grade 3 thrombocytopenia 30.9/3.9%; grade 3 anemia 14.5/3.9%. Non-haematological toxicity was similar, except for nausea and vomiting, (16.3/2%); renal toxicity (3.7/0%) and hepatic toxicity (5.6/12.7%). CONCLUSIONS: With a higher overall response rate and lower toxicity, GD is a good first treatment option for advanced NSCLC.

Weekly docetaxel as second-line therapy for patients with advanced breast cancer resistant to previous anthracycline treatment.

This phase II trial evaluated the efficacy and toxicity of weekly docetaxel as treatment of advanced metastatic breast cancer patients resistant to prior anthracycline chemotherapy. After the first 18 patients, the initial dose (40 mg/m2, 30-min i.v. infusion for 6 consecutive weeks, followed by 2-week rest) was reduced to 36 mg/m2 in the remaining 17 patients due to the incidence of toxicity (28% grade 3-4 asthenia). Overall response rate was 34% (95% CI, 19-50): two complete (6%) and ten partial responses (28%) were found. The median duration of response was 6.8 months, the median time to disease progression was 8.4 months, and the median overall survival was 13.6 months (median follow-up of 11.4 months). Neutropenia was the only severe hematologic toxicity (17% of patients), whereas asthenia, nail, ocular and skin disorders were the most common nonhematologic toxicities. Only one death during further follow-up was related to toxicity (caused by pulmonary fibrosis). In conclusion, we found weekly docetaxel to be an active and safe chemotherapy regimen for patients with metastatic breast resistant to previous anthracyclines. This weekly regimen caused minimal myelosupression, while retaining significant activity against advanced breast cancer. Both factors provide attractive possibilities for the development of combination therapies incorporating weekly docetaxel. Nevertheless, the number of patients receiving either dose (40 and 36 mg/m2) which we studied is low and our results require confirmation on larger groups of patients.

Gemcitabine, cisplatin and vinorelbine as induction chemotherapy followed by radical therapy in stage III non-small-cell lung cancer: a multicentre study of galician-lung-cancer-group.

PURPOSE: To determine the effectiveness of a gemcitabine-cisplatin-vinorelbine combination in patients with stage III non-small-cell lung cancer (NSCLC). PATIENTS AND METHODS: Patients (n=46) with stage III NSCLC and naive of therapy were recruited into the trial to receive gemcitabine (G, 1000 mg/m(2)) on days 1 and 8, cisplatin (C, 100 mg/m(2)) on day 1 and vinorelbine (V, 25 mg/m(2)) on days 1 and 8 every 21 days for three cycles. RESULTS: Two patients achieved complete response (CR) and 23 partial response (PR), overall response 52%. Subsequent radical surgery included nine patients of whom four were non-resectable and five were resected and with 1 CR. Radiotherapy was administered to 31 patients, and two achieved CR. The median time to progression and overall survival were 37 and 50 weeks, respectively. Grade 3-4 neutropenia and thrombocytopenia occurred in 35% of cycles, with two toxic deaths. Severe non-haematological toxicity was uncommon. CONCLUSIONS: This GCV combination is effective in patients with stage III NSCLC, and with an acceptable toxicity.

CHOP chemotherapy of intermediate and high-grade non-Hodgkin's lymphoma.

The results of CHOP treatment in 63 patients with intermediate and high-grade non-Hodgkin's lymphoma (Working Formulation D to I), Ann Arbor stage I to IV were analyzed. The response rate was 87%, 71% complete remission and 16% partial remission with a mean duration of 22 months. The 5-year actuarial survival was 61% (95% confidence interval, 51-70%). The treatment was well tolerated and no deaths due to acute toxicity were observed. Poor prognostic factors in univariate analysis were: high-grade histology, stages III and IV, B symptoms, > or = 4 affected lymph node regions, Karnofsky index < or = 70, erythrocyte sedimentation rate (ESR) > 60 mm, haemoglobin < 100 g/l and elevated lactic dehydrogenase (LDH). Poor prognostic factors in multivariate analysis were: high-grade histology, stages III and IV, haemoglobin < 100 g/l and elevated LDH. In summary, good results were obtained with CHOP chemotherapy, without severe toxicity.