Randomized phase 2 trial on refinement of early-stage NSCLC adjuvant chemotherapy with cisplatin and pemetrexed versus cisplatin and vinorelbine: the TREAT study.

Abstract

BACKGROUND:

Adjuvant chemotherapy is beneficial in non-small-cell lung cancer (NSCLC). However, balancing toxicity and efficacy mandates improvement.

PATIENTS AND METHODS:

Patients with completely resected stages IB-pT3N1 NSCLC were randomly assigned to either four cycles cisplatin (C: 50 mg/m(2) day (d)1 + 8) and vinorelbine (V: 25 mg/m(2) d1, 8, 15, 22) q4 weeks or four cycles cisplatin (75 mg/m(2) d1) and pemetrexed (Px: 500 mg/m(2) d1) q3 weeks. Primary objective was the clinical feasibility rate (no grade (G)4 neutropenia/thrombocytopenia or thrombocytopenia with bleeding, no G3/4 febrile neutropenia or non-hematological toxicity; no premature withdrawal/death). Secondary objectives were drug delivery and efficacy.

RESULTS:

One hundred and thirty two patients were randomized (stages: 38% IB, 10% IIA, 47% IIB, 5% pT3pN1; histology: 43% squamous, 57% non-squamous). The feasibility rates were 95.5% (cisplatin and pemetrexed, CPx) and 75.4% (cisplatin and vinorelbine, CVb) (P = 0.001); hematological G3/4 toxic effects were 10% (CPx) and 74% (CVb) (P < 0.001), non-hematological toxic effects were comparable (33% and 31%, P = 0.798). Delivery of total mean doses was 90% of planned with CPx, but 66% (cisplatin) and 64% (vinorelbine) with CVb (P < 0.0001). The median number of cycles [treatment time (weeks)] was 4 for CPx (11.2) and 3 for CVb (9.9). Time to withdrawal from therapy differed significantly between arms favoring CPx (P < 0.001).

CONCLUSION:

Adjuvant chemotherapy with CPx is safe and feasible with less toxicity and superior dose delivery compared with CVb.

• Authors: M Kreuter, J Vansteenkiste, J R Fischer, W Eberhardt, H Zabeck, J Kollmeier, M Serke, N Frickhofen, M Reck, W Engel-Riedel, S Neumann, M Thomeer, C Schumann, P De Leyn, T Graeter, G Stamatis, I Zuna, F Griesinger, M Thomas, TREAT investigators
• Journal: Annals of oncology : official journal of the European Society for Medical Oncology (Ann Oncol) Vol. 24 Issue 4 Pg. 986-92 (Apr 2013) ISSN: 1569-8041 [Electronic] England
• PMID: 23161898 (Publication Type: Clinical Trial, Phase II, Journal Article, Randomized Controlled Trial, Research Support, Non-U.S. Gov't)

Chemical References

• Glutamates
• Pemetrexed
• Vinblastine
• Guanine
• Cisplatin
• Vinorelbine

Topics

• Adult
• Aged
• Antineoplastic Combined Chemotherapy Protocols (administration & dosage, adverse effects)
• Carcinoma, Non-Small-Cell Lung (drug therapy, pathology)
• Chemotherapy, Adjuvant
• Cisplatin (administration & dosage, adverse effects)
• Disease-Free Survival
• Drug-Related Side Effects and Adverse Reactions (chemically induced, pathology)
• Female
• Glutamates (administration & dosage, adverse effects)
• Guanine (administration & dosage, adverse effects, analogs & derivatives)
• Humans
• Lung Neoplasms (drug therapy, pathology)
• Male
• Middle Aged
• Pemetrexed
• Survival Rate
• Vinblastine (administration & dosage, adverse effects, analogs & derivatives)
• Vinorelbine