Vinorelbine in Non-Small-Cell Lung Cancer

During the past 5 years, real strides have been made in the management of advanced non-small-cell lung cancer (NSCLC). The introduction of newer chemotherapeutic agents and novel treatment regimens is paving the way for marked improvements in both clinical outcomes and quality of life.

This investigators’ meeting on “Vinorelbine (Navelbine) in Non-Small-Cell Lung Cancer” provided an opportunity to review results from recent clinical trials, assess the implications of the emerging data, and share ideas on how we might build on these advances in the future.

In the first contribution, I examine the current state of the art in the management of unresectable non-small-cell lung cancer. Combined-modality treatment with chemotherapy plus irradiation is now the standard of care for patients with stage III, locally advanced disease. Still to be resolved is the issue of whether chemotherapy and radiation are best administered sequentially or concurrently. Most patients with stage IIIB disease and positive pleural effusion, as well as those with stage IV disease, are candidates for chemotherapy, which has undergone marked evolution with the identification of several new active agents. The combination of vinorelbine and cisplatin (Platinol) is currently a reasonable community standard. Other agents of interest are paclitaxel (Taxol), docetaxel (Taxotere), gemcitabine (Gemzar), irinotecan (Camptosar), and topotecan (Hycamtin). The results of recent and ongoing clinical trials of these therapies are reviewed.

Dr. John A. Hohneker presents a summary of safety data obtained in North American trials of vinorelbine. The studies conducted to date demonstrate that this agent is well tolerated and can easily be administered in the outpatient setting. Myelosuppression is the primary toxic effect, but the rate of hospitalization for granulocytopenic complications is low. The author’s analysis reveals a relatively low incidence of thrombocytopenia, symptomatic neuropathy, alopecia, and nausea and vomiting—all of which are noncumulative and reversible on drug discontinuation. This favorable safety profile has been maintained when vinorelbine has been given in combination with cisplatin.

An historical review of phase III trials with vinorelbine in non-small-cell lung cancer is offered by Dr. Mark A. O’Rourke. A multicenter European trial demonstrated greater efficacy and less toxicity with the combination of vinorelbine plus cisplatin than with vindesine plus cisplatin. In a multicenter North American trial, single-agent vinorelbine was associated with superior survival rates when compared with leucovorin plus fluorouracil (5-FU). The author suggests that the combination of vinorelbine plus cisplatin be given strong consideration as a reference treatment regimen in advanced non-small-cell lung cancer.

Dr. Antoinette J. Wozniak presents a preliminary report from a phase II Southwest Oncology Group (SWOG) trial comparing cisplatin with cisplatin plus vinorelbine in advanced non-small-cell lung cancer. The final results of this recently completed study will be reported elsewhere in the near future. Based on encouraging results from an interim analysis, a new SWOG trial is being conducted to compare cisplatin plus vinorelbine with paclitaxel plus carboplatin (Paraplatin) in non-small-cell lung cancer.

Dr. Alex Y. Chang and colleagues describe in vitro studies demonstrating dose- and sequence-dependent synergism between paclitaxel and vinorelbine. This work has prompted a clinical trial to evaluate combined treatment with these drugs in patients with stage IV, refractory non-small-cell lung cancer. The results obtained thus far demonstrate that the combination regimen of paclitaxel and vinorelbine is active and warrants further study. The authors also recommend that this combination be studied as first-line therapy for stage IV disease.

The use of new double- and triple-drug combinations for the palliative care of non-small-cell lung cancer is addressed by Dr. Everett E. Vokes and colleagues. In an attempt to achieve greater efficacy with less toxicity, this group has studied non-cisplatin-based regimens combining drugs that have been shown to have single-agent activity and more favorable safety profiles than cisplatin-based regimens. Promising results have been obtained in phase I/II studies of ifosfamide (Ifex) in combination with either vinorelbine or paclitaxel. A regimen combining all three agents is currently being evaluated.

Dr. Gregory A. Masters and colleagues present preliminary findings from a phase I study of concomitant cisplatin, vinorelbine, and radiation in patients with advanced chest malignancies. Previous research had suggested that benefit may be accrued from the radiosensitizing properties of these chemotherapeutic agents. The authors note that the data obtained thus far have shown myelosuppression to be the acute dose-limiting toxicity. Early responses have been noted, and the final analysis will examine response rates both inside and outside the field of radiation.

In the final article, Dr. Jeffrey Crawford reports on a phase I/II study of the combination of vinorelbine and carboplatin in patients with advanced non-small-cell lung cancer. The 1-year survival rate was comparable to that obtained with vinorelbine and cisplatin in large-scale, multicenter trials. The use of granulocyte colony-stimulating factor limited all the episodes of febrile neutropenia. The investigators concluded that this combination is a useful addition to the treatment choices for advanced non-small-cell lung cancer.

Taken together, the articles in this supplement attest to an ongoing commitment to the search for safer and more effective treatments for patients with non-small-cell lung cancer. It is hoped that the information presented here will spark continued progress in the future