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Objectives: The incidence of non-small cell lung cancer (NSCLC) is increasing among the elderly. We studied the toxicity and efficacy of a weekly schedule of gemcitabine and cisplatin in elderly patients with advanced NSCLC., Methods: Patients aged 70 years or above with advanced NSCLC were treated in a phase II prospective trial with gemcitabine 1,000 mg/m(2) and cisplatin 35 mg/m(2) on days 1, 8 and 15 every 28 days., Results: Forty-eight patients with a median age of 74 years (range 70-78) participated in the study. We observed 14 cases with partial response, 14 with stable disease and 16 with progressive disease, whilst 4 patients were not evaluable. By intention-to-treat analysis, partial response rate was 31.8% whilst progressive disease was 33.3%. Median survival was 9 months; 1-year survival probability was 34.4% and median time to progression was 4 months. Grade III-IV leukopenia was observed in 5/48 patients (10.4%), 20/48 patients (41.7%) had grade III-IV thrombocytopenia and 7/48 patients (14.6%) had grade III-IV anemia. One patient experienced grade III emesis and 2 patients had grade III-IV fatigue., Conclusions: At this dose and schedule the combination of gemcitabine and cisplatin appears to be an active and well-tolerated regimen for elderly patients with advanced NSCLC., (Copyright 2003 S. Karger AG, Basel)

Background: The combination of gemcitabine and cisplatin has proven effective in the treatment of advanced non-small-cell lung cancer (NSCLC). However, the optimal schedule for administration of the two drugs has not yet been determined. In this study we evaluated the activity and toxicity of a weekly gemcitabine and cisplatin schedule., Patients and Methods: Thirty-six untreated patients with stage IIIB IV NSCLC entered the study. Treatment consisted of gemcitabine 1000 mg/m2 i.v. and cisplatin 35 mg/m2 i.v., both given weekly on day 1,8, and 15, followed by one week of rest., Results: Ninety-seven courses (273 weekly administrations) were delivered. The median dose-intensity was 612 mg/m2 per week for gemcitabine (82%) and 21 mg/m2 per week for cisplatin (80%). All 36 of the patients were evaluable for toxicity, and 30 for response. Partial remissions were observed in 12 patients, for an overall response rate of 40% (95% confidence interval (95% CI): 22.5%-57.5%). Most of the partial remissions were seen in IIIB patients (54% of the stage IIIB and 22% of the stage IV patients responded). According to the intent-to-treat principle, the response rate was 33.3% (12 of 36 patients). The median response duration was 9.9 months (range 4-23) and the median survival time 11.8 months (range 1-24). World Health Organization (WHO) grade 3-4 myelotoxicity was: thrombocytopenia in nine patients (25%), neutropenia in six (16.6%) and anemia in six (16.6%); there was very little additional major toxicity., Conclusions: This regimen appears to be active and to have a favourable toxicity profile.

Twenty-one patients with advanced non-small cell lung cancer and low performance status (Karnofsky: 40-60) were treated with moderate doses of chemo-radiotherapy. Seven patients (33%) had partial response and a median survival time of 10 months; 5 patients (24%) had stable disease and a median survival time of 5 months; 9 patients (43%) had progression of disease and a median survival time of 6 months. Median survival time for the whole group was 7 months. Toxicity related to treatment was minimal and posttreatment performance status was: stable in 10 patients and improved in 5 responsive patients. We conclude that this therapeutic strategy has some efficacy in this category of patients although it failed to show substantial benefit in terms of survival.

Sixty-eight evaluable patients with advanced squamous cell carcinoma (48), large cell carcinoma (2) and adenocarcinoma (18) of the lung were treated with a six-drug regimen delivering two monthly alternated combinations. The combinations were cisplatin, adriamycin and cyclophosphamide (CAP) and methotrexate, etoposide and CCNU (MEC'). Following a minimum of two courses, the overall response rate was 22% (confidence limits, 12% to 32%) (15/68, 2 complete responses and 13 partial responses); 47% (32/68) had stable disease and 31% (21/68) had progressive disease. The responses lasted a median of 3 months (range, 1-15 months). The actuarial median survival was 11 months in responsive patients, 10 months in stable disease patients, and 5 months in progressive patients. The overall median survival obtained was 9 months (range, 2-28+ months). Toxicity was minimal, and subjective tolerance of the treatment appeared good. However, this alternating program did not improve response rate or survival.

Fifteen selected patients with advanced intrathoracic non-small cell lung cancer and solitary metastasis were treated by a combined program including craniotomy, brain and chest irradiation, and systemic chemotherapy. One patient died because of cerebral hemorrhage after the operation. Five patients failed to achieve neurologic benefit. Nine patients improved their neurologic grading, and the median duration of improvement was 10 months (range, 1-26 months). The responses to systemic treatment were: one complete response, three partial responses, six stable disease responses, and four progressive disease responses. The overall median survival was 6 months from craniotomy and 12 months from diagnosis. Five patients became long survivors; they had a survival time ranging between 12 and 26 months after craniotomy. In conclusion, one third of patients had a satisfactory response to treatment; this outlines the value of the combined aggressive therapeutic approach also performed in patients who had a highly unfavorable prognoses.

The cases of 36 patients with inoperable non-small cell lung cancers and similar anatomoclinical features were retrospectively analysed on the basis of treatment received (21 combined chemical and radiation therapy, 15 chemotherapy). The results showed 7 PR (partial response) 5 S (stable) 9 P (progression) in the group given combined chemical and radiation treatment; 2 PR, 7 S and 6 P in the group given chemotherapy alone. The patients with the best Performance Status produced the best PR figures (6/9) and the longest mean survival (10 months). Analysis of 9 patients in each group indicated that the length of survival is not affected by the timing or doses of drug treatment. Altogether the data support the view that no treatment has any influence on the prognosis for inoperable lung cancers.

Sixty-one patients affected by small cell lung cancer (SCLC) entered in the study. Eighteen had limited disease and 43 extensive disease. Treatment consisted of: induction chemotherapy with 3 courses of CAV (cyclophosphamide, adriamycin, vincristine) in limited disease patients or 2 courses of CAV plus 2 courses of DDP-VP16 (cisplatin, etoposide) in extensive disease patients, followed by chest radiotherapy and CNS prophylaxis in responsive patients. Subsequently, responders and stable patients received maintenance chemotherapy by the alternation of cycles of CAV, DDP-VP16 and C'MP (CCNU, methotrexate, procarbazine), which lasted 1 year or until relapse. Four of 17 limited disease patients (23%) obtained a CR and 11 (65%) a PR; their median survival was 11 months (range, 2+-36+). One of the 7 extensive disease patients (3%) achieved a CR and 19 (51%) a PR; their median survival was 6 months (range, 1-22). Median duration of response was 12 months for CR and 5 months for PR. Responders (CR and PR) survived 11.5 months versus 3.5 months for failures (P less than 0.05); 3/61 (5%) showed long-term survival, in the absence of disease. The overall median survival was 7 months (range, 1-36+). The main toxic effects were myelosuppression and vomiting (WHO grade 3). From our results, this program does not offer further substantial gains in patients with SCLC.

From April 1985 to September 1987, 92 patients with advanced NSCLC were randomized to receive cytotoxic chemotherapy, Arm A (treated), or supportive care, Arm B (control). Chemotherapy consisted of the CEP combination (cyclophosphamide 500 mg/m2 i.v. day 1; epirubicin 50 mg/m2 i.v. day 1; cisplatin 80 mg/m2 i.v. day 1) alternated every 4 weeks with the MEC' combination (methotrexate 30 mg/m2 i.v. day 1; etoposide 200 mg/m2 i.v. day 1; CCNU 70 mg/m2 per os, day 1) until progression. Eight-nine patients (44 treated and 45 controls) were eligible for survival and 77 evaluable for response (38 treated and 39 controls). Response rate was: in Arm A, 8/38 (21%) partial response, 20/38 (53%) stable disease and 10/38 (26%) progressive disease; in Arm B, 18/39 (46%) stable disease and 21/39 (54%) progressive disease. Median time to progression was 4 months (range = 1-14) for treated and 2 months (range = 1-9) for controls (P = 0.001). Median survival was 8.5 months (range = 1+ to 25) for Arm A versus 5 months (range = 1+ to 28+) for Arm B; this difference was not statistically significant (Breslow test: chi-square = 2.75, P = 0.097; Mantel-Cox: chi-square = 0.32, P = 0.56). Treatment related toxicity was gastrointestinal WHO grade 3 in 22/102 (22%) CEP courses and in 10/91 (11%) MEC' courses respectively. Other observed side-effects were not clinically important. From these data our treatment was not clearly superior to supportive care in prolonging survival. This suggests the need for the inclusion of a control group in future chemotherapeutic trials of NSCLC.