Alternating chemotherapy with etoposide plus cisplatin and topotecan plus paclitaxel in patients with untreated, extensive‐stage small cell lung carcinoma

Abstract

BACKGROUNDThe objective of this study was to test the response rate and toxicity of alternating chemotherapy in previously untreated patients with extensive‐stage small cell lung carcinoma (SCLC).METHODSPatients with histologically proven, extensive‐stage SCLC, with a performance status of 0–2, and who had received no prior chemotherapy were eligible. The design was a two‐stage, Phase II, multicenter trial. Treatment consisted of alternating chemotherapy every 3 weeks with etoposide (100 mg/m2 on Days 1–3) and cisplatin (30 mg/m2 on Days 1–3) on Cycles 1, 3, 5 and with topotecan (1 mg/m2 on Days 1–5) and paclitaxel (200 mg/m2 on Day 5) on Cycles 2, 4, and 6. Filgrastim support was given with Cycles 2, 4, 6.RESULTSForty‐four patients were eligible and evaluable. The primary toxicity was myelosuppression. The median absolute neutrophil count was 300/μL with 70% Grade 4 neutropenia. The median platelet count was 58,000/μL with 23% Grade 4 thrombocytopenia. Grade 4 nonhematologic toxicities occurred in 16% of patients. Overall toxicities were not different between the two regimens. There were no treatment‐related deaths. Complete or partial responses occurred in 34 patients (77%). The median time to progression was 6.9 months, with a median survival of 10.5 months and with 1‐year and 2‐year survival rates of 37% and 12%, respectively.CONCLUSIONSThe regimen of alternating chemotherapy was associated with substantial myelosuppression and resulted in a high response rate and good overall survival. The results were similar to those reported in prior trials and did not suggest any improvement in therapy for patients with SCLC. Cancer 2003;10:2498–503. © 2003 American Cancer Society.DOI 10.1002/cncr.11377

Synergistic interaction of hyperthermia and gemcitabine in lung cancer

“…A CI of > 1 implies antagonism, = 1 is additivity, and < 1 synergy. 34 Clonogenic assay. Aliquots of cells were harvested 4 h after each intervention and plated at low concentrations (10 2 cells per 100-mm plate); multiplicity was determined and then cells were allowed to grow for seven days without being disturbed; cells (colonies) were then fixed with Carnoy's fixative and stained with methyl blue.…”

Topotecan in the First-Line Treatment of Small Cell Lung Cancer

“…In a phase II clinical trial, Jett et al [38] investigated the safety and efficacy of six alternating 21-day cycles of etoposide/cisplatin and topotecan/paclitaxel in previously untreated patients with extensive SCLC. The administration schedule for the first of the two alternating cycles was etoposide (100 mg/m ) on day 5 with G-CSF support.…”

“…Despite the theoretical advantages, alternating treatment regimens have, to date, failed to generate any efficacy benefits above those of therapeutic doublets in the SCLC setting [38,39] and have resulted in considerable toxicity. Further investigations are necessary to determine what role, if any, such regimens will play in the future treatment of patients with SCLC.…”

“…Survival of the overall patient population was consistent with that seen for PE therapy alone. The addition of topotecan consolidation therapy after treatment with four 38 Topotecan in First-Line SCLC /day) on days 1-3 of a 21-day cycle was investigated in a phase I trial [45]. The results from that trial are preliminary, but-in contrast to the results from the PE trials-topotecan treatment resulted in PRs in some patients who had not responded to the initial PE therapy [45].…”

Paclitaxel/Carboplatin/Etoposide Versus Paclitaxel/Topotecan for Extensive-Stage Small Cell Lung Cancer: A Minnie Pearl Cancer Research Network Randomized, Prospective Phase II Trial

“…The addition of paclitaxel to a platinum and etoposide is at least as efficacious, although more toxic, than a platinum plus etoposide [8][9][10][11][12]. Paclitaxel doublet combinations have been developed, including paclitaxel plus topotecan, and have been associated with relatively high response rates [2-4, [13][14][15]. The combination of paclitaxel and topotecan may offer advantages over platinum-based chemotherapy.…”