Single-Agent Paclitaxel in the Treatment of Advanced Non-Small Cell Lung Cancer

Abstract

Paclitaxel was the first identified member of a new class of anticancer drugs known as the taxanes. This compound has significant single-agent activity against a number of solid tumors including nonsmall cell lung cancer (NSCLC). In the first-line setting, single-agent paclitaxel has been studied on a number of different schedules and dose levels. Initial studies were done on the 24-h infusion schedule with doses of 200-250 mg/m 2 . Response rates were 21%-24%. Median survival ranged from six to nine months with one-year survival rates of 38%-42%. The major toxicity of this infusion schedule was myelosuppression, mainly neutropenia. Subsequent single-agent studies employed shorter infusion durations (three hours), with doses ranging from 175-225 mg/m 2 . The cumulative experience of the 3-h infusion schedule shows an overall response rate of 28.5% with median survival of 6-11 months and a one-year survival of 37.5%. Similar results were obtained in the one study examining the 1-h infusion schedule with doses ranging from 135-200 mg/m 2 . The major toxicities of the shorter infusion schedule include neutropenia, neuropathy, and myalgia/arthralgia syndrome. Weekly administration of paclitaxel also showed significant activity in advanced, metastatic NSCLC. Overall response rates have ranged from 30%-56% in the phase I/II setting with one-year survival rates of 42%-53%. A recently completed phase III trial comparing single-agent paclitaxel at 200 mg/m 2 over three hours every three weeks to best supportive care (BSC) in advanced or metastatic NSCLC has shown a survival advantage for the single-agent paclitaxel arm (median survival 6.8 months for paclitaxel versus 4.8 months for BSC, p = 0.045). An ongoing phase III trial is comparing singleagent paclitaxel to the combination of carboplatin and paclitaxel (CALGB 9730) in advanced, metastatic NSCLC. Paclitaxel has also been studied in the secondline setting. Infusion schedules have ranged from 1 h, 24 h and 96 h on an every-three-week schedule. Weekly paclitaxel has also been evaluated in the second-line setting. Although the overall experience is limited, response rates have ranged from 0%-38%. The overall role of single-agent paclitaxel in prolonging survival and improving quality of life remains uncertain in this setting.The cumulative experience of single-agent paclitaxel in advanced, metastatic NSCLC suggests that it is a highly active cytotoxic agent in this setting. The consistent finding of a 35%-40% one-year survival rate is notable. The major toxicities include neutropenia, neuropathy, and myalgia/arthralgia syndrome. Given the overall activity and impact on survival along with an acceptable toxicity profile, single-agent paclitaxel warrants comparison to other active agents and combination regimens in advanced, metastatic NSCLC.

Weekly Paclitaxel in Elderly Patients (Aged ≥ 70 Years) with Advanced Non–Small-Cell Lung Cancer: An Alternative Choice? Results of a Phase II Study

“…Paclitaxel every 3 weeks has been demonstrated to achieve significant activity as first line in advanced NSCLC, with responses ranging from 10%-38% and median survival from 6 months to 11 months. 10 The common dose was 200-225 mg/m² every 3 weeks (often in combination with carboplatin), with moderate or severe neutropenia and neurologic toxicity. To reduce these toxicities and improve qual-ity of life, paclitaxel has been administered in a weekly fashion; this schedule offers a theoretical advantage in terms of cytotoxicity as a result of prolonged cellular exposure to paclitaxel with lower toxicity.…”

Improvement of Oral Drug Treatment by Temporary Inhibition of Drug Transporters and/or Cytochrome P450 in the Gastrointestinal Tract and Liver: An Overview

“…This is comparable with the literature, as were the median time to progression of 3.5 months and median overall survival of 6 months. These studies, in which several single agents such as vinorelbine, gemcitabine, and the taxanes were used, revealed response rates between 8%-40% and median overall survival ranged from 6-11 months [123][124][125][126][127][128].…”

Efficacy and safety of weekly intravenous nanoparticle albumin‐bound paclitaxel for non‐small cell lung cancer patients who have failed at least two prior systemic treatments

“…Paclitaxel is one of the most widely used and effective antitumor agents derived from natural sources and plays an important role in non‐small‐cell lung cancer (NSCLC) . Traditional solvent‐based paclitaxel is associated with hypersensitivity reactions to the polyoxyethylated castor oil in which it is dissolving.…”