Chemotherapy of non small cell lung cancer. A prospectively randomized study of cisplatin-etoposide versus cisplatin-mitomycin-vinblastine

Based on preclinical studies showing synergism between cisplatin and etoposide, we randomized patients with non small cell lung cancer (NSCLC) to receive either the above combination (cisplatin 100mg/m(2) day 1, etoposide 130mg/m(2) days 1-3) or the combination of cisplatin-mitomycin-e and vinca drugs (MVP) (cisplatin 100mg/m(2), vinblastine 6mg/m(2), mitomycin 10mg/m(2) day 1), a regimen with a steady response rate. Partial responses were achieved in 12/44 (27%) of the cisplatin-etoposide group and in 11/43 (26%) of the MVR group. No difference in median survival could be demonstrated between the two groups (36 weeks versus 38 weeks). Myelotoxicity and alopecia were more severe in the cisplatin-etoposide group. Compared to international experience both regimens exhibited a relatively low response rate. It seems that for NSCLC new agents are required

Outcome of patients with brain metastases after combined modality therapy in small cell lung cancer (SCLC): A retrospective study

The authors evaluated the role of whole brain radiotherapy (WBRT) on the outcome of brain metastasis and survival in 41 patients with small cell lung cancer (SCLC) treated in their department. In addition to chemotherapy, radiotherapy was given to the primary site in all responder patients. Six patients presented brain metastasis initially and 10 patients after the fourth course of chemotherapy. Brain metastases were symptomatic in 12 of 16 patients with a median time of 5 months (1-14) until symptoms developed. All patients but 2 with brain metastasis received WBRT (30 Gy in 10 fractions) in addition to chemotherapy. The median survival time of patients with brain metastasis was 8.3 months (3.5 to 16) compared to 12 months (4 to 34+) for patients without brain metastasis. In addition, the median survival time for patients with brain metastasis who responded to systemic chemotherapy was better than that of nonresponders. The authors found no improvement in survival in patients who received concomitant WBRT after chemotherapy compared to patients who received WBRT after completion of chemotherapy. In conclusion, the role of consolidating cranial irradiation in addition to chemotherapy in SCLC patients is unclear and warrants prospective randomized studies. © 1995 E.I.F.T. srl - Firenze

Optimal duration of chemotherapy in small cell lung cancer: A randomized study of 4 versus 6 cycles of cisplatin-etoposide

With the purpose of investigating whether the 6-course standard dose treatment of etoposide-platinum (EP) in small cell lung cancer could be reduced to 4 courses without compromising patient's survival, 70 patients were randomized to receive either 4 or 6 cycles of etoposide 120 mg/m2 i.v. days 1-3 and cisplatin 80 mg/m2 day 1. With the intention of comparing these two durations as primary treatment policies, patients were randomized on admission and not after the fourth course. From the 69 evaluable patients 34 received EPx4 cycles and 35 EPx6 cycles. Objective response for EPx4 was achieved by 21 patients (62%, 95% CI 44%-78%) compared to 24 patients (69%, 95% CI 51%-83%) of the EPx6 group. Median times to progression were 6 mo (4-19) and 7 mo (4-40) respectively (P = 0.06) in the two groups. Median survivals were 8.5 mo (4-28.5) and 9.5 mo (4-51) (p = 0.04) respectively. No differences in the survival of limited-disease patients were shown with 10.5 mo (6-28.5) and 12 mo (8-51) respectively, in the two groups. Patients with extensive disease had a trend favoring prolonged chemotherapy with a median survival of 9 mo (5-16) versus 6.5 mo (4-16.5) for those in the EPx4 group (p = 0.09). Toxicity was not significantly more severe in the EPx6 group. In conclusion, patients achieving complete response within 4 cycles may not need continued chemotherapy, but patients with extensive disease may benefit from 2 more cycles

Sequential versus alternating administration of cisplatin/etoposide and topotecan as first-line treatment in extensive-stage small-cell lung cancer: Preliminary results of a phase III trial of the hellenic oncology research group

Background: This trial was designed to compare the efficacy and toxicity of sequential versus alternating administration of cisplatin/etoposide and topotecan in patients with previously untreated extensive-stage small-cell lung cancer (SCLC). Patients and methods: Two hundred eighty-four chemotherapy-naive patients were randomized between the sequential therapy arm (n = 142; 4 cycles of cisplatin 75 mg/m2 intravenously [I.V.] on day 1 with etoposide 100 mg/m2 per day I.V. on days 1-3 followed by 4 cycles of topotecan 1.5 mg/m2 per day I.V. on days 1-5) and the alternating arm (n = 142; same doses of cisplatin/etoposide on cycles 1, 3, 5, and 7 and topotecan on cycles 2, 4, 6, and 8). Treatment cycles for both regimens were administered every 3 weeks. Results: At this preliminary analysis, no statistically significant difference in the overall response rate, duration of response, time to disease progression, or median survival was observed between the 2 arms. A total of 756 cycles of the sequential therapy and 830 cycles of the alternating therapy were administered, with a median numbers of 6 and 7 cycles per patient, respectively. Topotecan was administered in 85 patients on the sequential arm and 132 patients on the alternating arm. Dose reductions for toxicity were similar in both arms. Grade 3/4 toxicities in the sequential and alternating arms, respectively, included neutropenia (51% and 52%; P = NS), anemia (12% and 11%; P = NS), febrile neutropenia (7% and 9%; P = NS), thrombocytopenia (19% and 20%; P = NS), and asthenia (8% and 2%; P = 0.02). There were 4 toxicity-related deaths in the sequential arm versus 3 in the alternating arm. Conclusion: Our preliminary conclusion is that the sequential and alternating regimens resulted in comparable activity and tolerability in previously untreated patients with extensive-stage SCLC