Use of vinorelbine in non-small-cell lung cancer. Provincial Lung Disease Site Group

Is there a role for the use of vinorelbine in the treatment of patients with non-small-cell lung cancer (NSCLC)?

To make recommendations about the use of vinorelbine in the management of patients with NSCLC.

Survival is the primary endpoint of interest. Response and toxicity are secondary endpoints.

Evidence was selected and reviewed by the 4 members of the Lung Disease Site Group (Lung DSG). Early drafts of this practice guideline were reviewed by the Lung DSG and by the Systemic Treatment Program Committee (STPC). These committees comprise medical and radiation oncologists, pathologists, surgeons, epidemiologists, pharmacists, nurses, a psychologist, a medical sociologist and administrators. No consumers participated in the development of this guideline.

Only evidence from randomized controlled trials (RCTs) and phase II studies was evaluated. Six RCTs and 5 phase II studies were reviewed and are discussed in this report. Of the 6 RCTs, 3 have been fully published.

Vinorelbine, either as a single agent or in combination with cisplatin, produces higher response rates (12%-37%) than other single agent vinca alkaloids (10%-20%) in patients with previously untreated NSCLC. Two of 3 RCTs that reported survival differences demonstrated a survival benefit for previously untreated patients with NSCLC when treated with vinorelbine in combination with cisplatin as compared with patients treated with either vindesine plus cisplatin (p = 0.04) or leucovorin plus 5-fluorouracil (p = 0.03). The third study reported no statistically significant difference between patients treated with vinorelbine alone and those receiving vinorelbine plus cisplatin.

The major toxic effects are hematologic. Neutropenia is the dose-limiting toxic effect. However, there is less neurotoxicity than with other vinca alkaloids (e.g., vindesine) and less nausea and vomiting than with other active agents used in the treatment of NSCLC.

Evidence from randomized controlled trials supports the use of vinorelbine as an option for the first-line treatment of patients with locally advanced or metastatic NSCLC. Whether vinorelbine is used as a single agent or in combination with cisplatin depends on the anticipated trade-offs between the expected symptomatic benefits of a higher response rate with the combination (as seen in randomized controlled trials) and the increased toxicity. Evidence for a possible survival advantage for the combination of vinorelbine and cisplatin over vinorelbine alone is conflicting. There is insufficient evidence at the present time to advocate the use of vinorelbine in previously treated patients who have recurrent or progressive disease. Similarly, there is insufficient evidence at the present time to advocate the use of vinorelbine as adjuvant or induction therapy for patients with stage I, II or early stage III disease. The enrolment of patients with NSCLC in clinical trials is encouraged.