A phase II study of paclitaxel in heavily pretreated patients with small-cell lung cancer

Abstract

Summary The purpose of the study was to delineate the efficacy and toxicity of paclitaxel (Taxol, Bristol Myers Squibb) in the treatment of drug resistant small-cell lung cancer (SCLC). Patients with SCLC relapsing within 3 months of cytotoxic therapy received paclitaxel 175 mg m-2 intravenously over 3 h every 3 weeks. The dose of paclitaxel was adjusted to the toxicity encountered in the previous cycle. Of 24 patients entered into the study, 24 and 21 were assessable for response and toxicity respectively. There were two early deaths and two toxic deaths. No complete and seven partial responses (29%) (95%CI 12-51%) were observed and five patients had disease stabilization. The median survival (n = 21) was 100 days. Life-threatening toxicity occurred in four patients; in others (non)-haematological toxicity was manageable. Paclitaxel is active in drug-resistant SCLC. Further investigation in combination with other active agents in this poor prognosis group is appropriate.Keywords: small cell lung cancer; chemotherapy; early relapse With present-day chemo-and radiotherapy regimens, a major response with considerable prolongation of survival (Ihde, 1992) will be achieved in 90-95% of patients with small-cell lung cancer (SCLC). However, in the majority of these patients the tumour will relapse after a shorter or longer treatment-free period. In this situation, second-line treatment is necessary for adequate palliation. A multifocal relapse will usually lead to treatment with chemotherapy (Andersen et al, 1990). It is then necessary to distinguish between patients with tumours that are sensitive and patients with tumours presumably resistant to cytotoxic agents used in the induction phase (Giaccone, 1989). Patients relapsing within 3 months of induction chemotherapy are considered resistant to the drugs used in the induction regimen (Postmus et al, 1987;Smit et al, 1989). For such patients, second-line treatment should consist off non-cross-resistant drugs. The poor results currently obtained by second-line chemotherapy support the view that failure to identify real non-cross-resistant agents is the primary reason for lack of success (Andersen et al, 1990). Further evidence for this view comes from the fact that, although in most studies on second-line chemotherapy it is not specifically stated, most therapy-resistant patients responding to a second-line regimen have shown a previous response of short duration to first-line treatment (Smit et al, 1989;Postmus, 1993). Thus, there is a great need for new active agents in the setting of second-line treatment in so-called therapy-resistant patients. Moreover, identification of such agents may lead to the development of more potent first-line regimens.

Small Cell Lung Cancer: Current Therapy and Promising New Regimens

“…Recently, topotecan was approved by the U.S. patient relapses while on therapy or has been off therapy fewer than 2-3 months, his response to topotecan or any other chemotherapy regimen is generally <10% [32]. There are multiple single-agent studies demonstrating activity for recurrent SCLC with response rates ranging from 11%-40% [33][34][35][36][37][38]. These agents include irinotecan, docetaxel, paclitaxel, topotecan, vinorelbine, and carboplatin.…”

Epirubicin/paclitaxel/etoposide in extensive-stage small-cell lung cancer: a phase I–II study

“…Among the last generation drugs, paclitaxel is particularly noteworthy; this drug is highly active in various malignancies and its documented activity, in refractory patients, makes it especially interesting for testing in SCLC (Smit et al, 1998). The experience with paclitaxel, in the treatment of SCLC, is still limited but promising: available data from literature strongly suggest a high antitumour activity of paclitaxel-based regimens, with toxicity profiles which vary according to the different drugs used in combination.…”

“…This drug showed encouraging single-agent activity as second-line treatment: in patients with ED pretreated with CDE as first-line combination, single-agent paclitaxel showed an overall response rate of 29%, which is at the upper level of activity for any single agent in this setting (Smit et al, 1998). An interesting activity was also observed in untreated patients; in the Eastern Cooperative Oncology Group (ECOG) phase II study a 34% remission rate and a 43-week median survival were observed (Ettinger et al, 1995); the North Central Cancer Treatment Group (NCCTG) also reported a 53% response rate in 43 untreated patients (Kirschling et al, 1999).…”

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

“…The demonstrated activity of these two new drugs (topotecan and paclitaxel) in the middle 1990s with novel mechanisms of action against SCLC prompted us to reevaluate the hypothesis of alternating noncross-resistant chemotherapy. Although it is debatable whether the drugs employed in our trial truly are noncross resistant, it is clear that both topotecan 8,9 and paclitaxel 10 have activity against SCLC when they are employed as second-line agents in patients who have failed initial therapy with etoposide and cisplatin. We also were encouraged by the high response rate to topotecan and paclitaxel in previously untreated patients.…”

“…8,9 In a second-line setting, paclitaxel had a 29% response rate in heavily pretreated patients. 10 Those studies suggested that, from a clinical perspective, topotecan and paclitaxel may be noncross resistant with etoposide and cisplatin.…”