Phase II trial of a 3-hour infusion of paclitaxel in previously untreated patients with advanced non-small-cell lung cancer.

Abstract

PURPOSE To determine the antitumor activity and toxicity of paclitaxel administered as a 3-hour infusion in patients with advanced non-small-cell lung cancer (NSCLC). PATIENTS AND METHODS Fifty-one patients with advanced measurable or assessable NSCLC and performance status 0 to 2 who had not received prior chemotherapy were treated with paclitaxel 175 mg/m2 over 3 hours with premedication. Cycles were repeated every 3 weeks for a maximum of nine cycles. Most patients had prior radiotherapy (57%), extrathoracic metastatic disease (65%), and measurable disease (75%). Twenty-two percent had previously untreated stage III disease. RESULTS The objective response rate was five of 51 (10%; 95% confidence interval, 3% to 21%). No subgroup with a higher response rate could be identified. There were no complete responses (CRs) and all responses lasted less than 5 months. Treatment was well tolerated with brief World Health Organization (WHO) grade IV neutropenia in only 16% of patients. Grade III/IV myalgia/athralgia occurred in 22% of patients. No significant hypersensitivity reactions occurred. CONCLUSION The antitumor activity of this dose and schedule appears inferior to that reported in previously published phase II trials in NSCLC that used higher doses of paclitaxel infused over 24 hours, although confidence intervals for response overlap. Determining the optimal dose and schedule for using paclitaxel in NSCLC requires further investigation, and these results should caution against using shorter infusions outside appropriate clinical trials.

Neutropenic Enterocolitis in Lung Cancer: A Report of Two Cases and a Review of the Literature

“…In the previous phase II studies evaluating a single-agent regimen of paclitaxel or docetaxel, the incidence of mucositis or diarrhea (grade 3 or more) was at most 6% (range 0-6%) (13,14). However, several cases of neutropenic enterocolitis have been reported in patients with solid tumors treated with taxane-based combination chemotherapy (6)(7)(8)(9)(10)(11), and single-agent vinorelbine chemotherapy (8).…”

Feasibility of Oral Topotecan Plus Intravenous Paclitaxel in Advanced Non-Small-Cell Lung Cancer

“…First, both agents have novel mechanisms of action: topotecan inhibits topoisomerase I, an enzyme required for cellular replication and repair, whereas paclitaxel interrupts the reorganization of the microtubule network necessary for normal mitotic function. Second, both agents have demonstrated single-agent tumor activity in NSCLC [10, 15, 16]. Third, the DLTs of topotecan and paclitaxel are well known, and the combination of the 2 agents was not expected to lead to untoward cumulative toxicity.…”

“…Paclitaxel has likewise gained acceptance as an important treatment option for NSCLC patients, with response rates ranging from 10–38% [15, 16]and 1-year survival rates of 35–40% [17]. Paclitaxel (175–225 mg/m 2 ) is given in a 3-hour i.v.…”

Dose-intense therapy with etoposide, ifosfamide, cisplatin, and epirubicin (VIP-E) in 107 consecutive patients with limited- and extensive-stage non-small-cell lung cancer

“…Improvements in patient selection, supportive care, and perhaps utilization of new chemotherapy agents [12,22,32,39,43,48,75], will be required before testing against established protocols can be justified. Similar qualifications apply to the role of HDC in NSCLC, whose role remains experimental in view our findings.…”