Phase II study of nitrosourea fotemustine as single-drug chemotherapy in poor-prognosis non-small-cell lung cancer.

A phase II study was designed to evaluate objective response rate and toxicity of fotemustine as single-drug chemotherapy in non-small-cell lung cancer. Eighty-seven patients with unresectable non-small-cell lung cancer took part in the study. Seventy-seven were evaluable for response. Of these, 60% had received prior chemotherapy and 74% had metastatic disease. Moreover, 22 patients had central nervous system metastases (of whom 12 were evaluable for this site). Treatment consisted of fotemustine 100 mg m-2 administered on days 1 and 8 followed by a 5 week rest period. Afterwards, responding or stabilised patients received fotemustine 100 mg m-2 every 3 weeks as a maintenance therapy. Toxicity and quality of life were recorded during therapy. Thirteen patients (17%; 95% CI 9-25%) had an objective response (11% for pretreated, 26% for non-pretreated) with a median duration of 22 weeks (range 7-41 weeks). Two objective responses were observed among the 12 patients with evaluable brain metastases. No response was observed among the 14 patients with adenocarcinoma. Haematological, gastrointestinal, hepatic and renal toxicities were mild to moderate and manageable. The most frequent biological adverse reactions were delayed thrombocytopenia and neutropenia. Quality of life did not significantly decrease during the first 6 treatment weeks. Moreover, it remained stable during the study period in patients with response or stabilisation, whereas it significantly decreased in patients who experienced progression of the disease. Fotemustine is feasible for single-drug chemotherapy in non-small-cell lung cancer even though poor prognostic variables such as brain metastases are present. It can be administered on an outpatient basis and toxicity is moderate and manageable. Thus, fotemustine can be considered as a putative drug in further combinations.

Alternating radiotherapy and chemotherapy schedules in limited small cell lung cancer: analysis of local chest recurrences.

An analysis of the chest recurrences was conducted in 72 consecutive patients with limited small cell lung cancer treated in two successive phase II trials alternating six induction chemotherapy courses and three series of thoracic radiotherapy, followed by maintenance chemotherapy. The total radiation dose was 45 Gy (3 series of 15 Gy) in the first trial, and 55 (20, 20 and 15 Gy) in the second. The effect of the irradiated volume was investigated by comparing the local relapse rates in the group of patients treated by radiation fields encompassing the initial tumor volume to another group in which the initial target volume was not fully covered by radiation fields. The definition of these two groups was performed retrospectively by examination of radiological, fiberoptic bronchoscopy initial findings, technical radiation charts and check films. The local recurrence rate were 33 and 36% in each group (no significant difference). This finding could suggest that tumor shrinkage after chemotherapy might allow the use of "reduced" radiation volumes. However, the limited number of patients does not permit a definite conclusion. The effect of radiation dose was investigated by comparing the local control rates in the two consecutive trials which delivered 45 and 55 Gy, respectively. No difference in long-term local control was found: the addition of 10 Gy in the second trial only seemed to delay the appearance of local recurrences by 6 months. Twenty percent of patients died from a local relapse without evidence of distant metastases.(ABSTRACT TRUNCATED AT 250 WORDS)

Alternating radiotherapy and chemotherapy in 173 consecutive patients with limited small cell lung carcinoma. GROP and the French Cancer Center's Lung Group.

One-hundred seventy-three patients with limited small cell lung cancer were included in three consecutive protocols alternating radiotherapy and chemotherapy. The alternating schedule consisted of six courses of chemotherapy (doxorubicin, VP16213, cyclophosphamide, and methotrexate in the first protocol; methotrexate being replaced by cisplatinum in the other two protocols) and three series of thoracic radiotherapy delivering a total dose of 45, 55, and 65 Gy in each consecutive protocol. Radiotherapy was started after the second course of chemotherapy. A 1-week gap was respected between each course of chemotherapy and each series of radiotherapy. Seventy percent of patients were in complete remission at the end of the induction treatment. The actuarial 5-year local control was 60% and the 5-year overall survival was 18%. Sixty percent of patients developed distant metastases. The death rate unrelated to cancer was 10%. These results show that alternating radiotherapy and chemotherapy schedules are reproducible, and provide a consistent long-term local control and a long-term survival rate exceeding 15% in limited disease.

Combination of chemotherapy and radiotherapy in limited small cell lung carcinoma: results of alternating schedule in 109 patients.

One hundred nine patients with limited small cell lung carcinoma were entered in a phase II study of treatment consisting of alternating 6 cycles of combination chemotherapy and 3 courses of mediastinal radiotherapy. Chemotherapy consisted of 40 mg doxorubicin/m2 on day 1; 75 mg etoposide/m2 on days 1, 2, and 3; 300 mg cyclophosphamide/m2 on days 3, 4, 5, and 6; and 400 mg methotrexate/m2 on day 2 (plus folinic acid rescue) or 100 mg cisplatin/m2 on day 2. The total mediastinal radiation dose was 45 or 55 Gy. A 6- to 8-cycle maintenance chemotherapy followed this induction protocol. The complete remission rate at the end of the induction therapy was 79%. The local recurrence rate was 25%, and the distant metastases rate was 52%. Median survival is 17.2 +/- 1.2 months and survival rate at 3 years is 26%. Lethal toxicity occurred in 3% of the patients, and long-term survivors are being evaluated. Our results justify further investigations with this alternating schedule.

[Chemo-radiotherapy combination in small cell bronchial carcinomas. Limitations and results in 109 patients treated with an alternating protocol]. / Association chimio-radiothérapique dans les carcinomes bronchiques à petites cellules. Limites et résultats chez 109 malades traites avec un schéma d'alternance.

One hundred and nine patients with limited small cell lung carcinoma were entered in a phase II study alternating six cycles of combination chemotherapy and three courses of mediastinal radiotherapy. Chemotherapy consisted of doxorubicin 40 mg/m2 day 1, etoposide 75 mg/m2 days 1, 2, 3, cyclophosphamide 300 mg/m2 days 3, 4, 5, 6, and methotrexate 400 mg/m2 day 2 (+folinic acid rescue) or cisplatin 100 mg/m2 day 2. The total mediastinal radiation dose was 45 or 55 Gy. A 6 to 8 cycle maintenance chemotherapy followed this induction protocol. The complete remission rate at the end of the induction therapy was 79%. The local recurrence rate was 25% and the distant metastases rate was 52%. Median survival is 17.2 +/- 1.2 months and survival rate at 3 years is 26%. Lethal toxicity occurred in 3% of patients during induction therapy, and long term survivors are being evaluated. Our results justify further investigations with this alternating schedule.