A prospective randomized trial of adjuvant vinorelbine and cisplatin in completely resected stage IB and II non-small cell lung cancer. Intergroup JBR10

English

Reviewer: S. Jack Wei, MD
Abramson Cancer Center of the University of Pennsylvania
Ultima Vez Modificado: 6 de junio del 2004

Presenter: Timothy Winton
Presenter's Affiliation: National Cancer Institute of Canada
Type of Session: Scientific

Background

Recent studies have shown that adjuvant chemotherapy following complete resection of non-small cell lung cancer (NSCLC) improves overall survival
The majority of this benefit has been seen in patients with higher stage disease.
The role of adjuvant chemotherapy is less clear in patients with stage I and II disease
This study was designed to examine whether the addition of vinorelbine and cisplatin is superior to observation alone for overall survival of patients with complete resection of stage IB and II NSCLC

Materials and Methods

Patients with T2N0, T1N1, or T2N1 NSCLC were enrolled in the study (T3N0 patients were excluded) from July 1994 to April 2001
All patients were ECOG performance status (PS) 0-1 and underwent complete surgical resection. Patients undergoing segmentectomy or wedge resection were excluded
Following surgery, patients were randomized to observation or adjuvant chemotherapy
Adjuvant chemotherapy consisted of cisplatin (50 mg/m2, d1&8) q 4 wks x 4 cycles with vinorelbine. Initially vinorelbine dose was 30 mg/m2 qwk x 16 wks but was reduced in August 1995 to 25 mg/m2 qwk x 15 wks due to hematologic toxicities

Results

482 patients were randomized, 41 patients excluded, leaving 441 patients analyzed
Patient groups were well balanced in terms of age, gender, PS, histology, stage, extent of resection, and presence of RAS mutation
65% of patients received 3 or 4 cycles of chemotherapy (median = 3 cycles)
77% of patients required at least one dose reduction, mostly due to neutropenia
5-year recurrence-free survival (RFS): 48% vs. 61% (p=0.012)
Median RFS: 46.7 mo vs. non-yet-reached (p=0.0004) (hazard ratio = 0.61)
5-year overall survival (OS): 69% vs. 54% (p=0.0022)
Median OS: 73 mo vs. 94 mo (p=0.012) (hazard ratio = 0.7)
Grade 3 or 4 granulocytopenia was seen in 73% of patients
7% of patients experienced grade 3 or 4 febrile neutropenia

Author's Conclusions

Vinorelbine and cisplatin can be administered safely after complete resection of NSCLC
With the exception of neurotoxicity, the impact of chemotherapy on QOL was small and generally reversible
Adjuvant cisplatin and vinorelbine result in significantly improved RFS and OS in stage IB and II NSCLC patients

Clinical/Scientific Implications

This study combined with the CALGB study also presented at this conference provide convincing evidence that the addition of adjuvant chemotherapy to completely resected early stage NSCLC improves relapse-free and overall survival. It is unclear why this study shows a dramatic improvement in survival when other similar studies have failed to do so. This study included both stage IB and II patients and was conducted in conjunction with several other cooperative groups including ECOG, SWOG, and CALGB. The patient population does not appear to be particularly favorable compared to previous studies. It is possible the use of more modern chemotherapy may contribute to this benefit. Regardless, these studies along with recently reported data by the International Adjuvant Lung Cancer Trial (IALT) (which showed a small but significant survival benefit for cisplatin-based chemotherapy in completely resected stage I-III NSCLC) have established adjuvant chemotherapy as the standard of care in this group of patients.

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