|
Advertisement |
|
|
||
 |
|
|||||
|
|||||
|
 |
||||||
|
||||||
|
||||||
|
Journal of Clinical Oncology, Vol 22, No 7 (April 1), 2004: pp. 1345-1347 © 2004 American Society of Clinical Oncology. DOI: 10.1200/JCO.2004.99.228
Should We Discard Vinorelbine Plus Cisplatin From the First-Line Therapy of Advanced Non–Small-Cell Lung Cancer?Institute of Oncology Bucharest, Bucharest, Romania To the Editor: I read with great interest the paper published by Fossella et al,1 reviewed by Harper et al,2 in the August 15, 2003 issue of the Journal of Clinical Oncology, evaluating the results of a phase III trial comparing docetaxel (DOC) plus platinum combination (cisplatin [CDDP] or carboplatin) versus vinorelbine (VNR) plus CDDP (VC) for advanced non–small-cell lung cancer (NSCLC). Basically, the results of the trial suggest the superiority of DOC over the VNR combination, not necessarily based on the antitumor activity, but more strongly related to the toxicity profile and the significant improvement on quality of life (QoL). Despite the very careful analysis of the data, I feel reluctant to accept the final recommendation of Harper et al, who stated that "cisplatin and vinorelbine should no longer be considered a standard first-line therapy in the management of advanced NSCLC." My arguments against such a recommendation would be as follows: (1) Large scale randomized phase III trials have shown an equivalent antitumor activity of the VC combination compared with other new standard platinum-based doublets for advanced NSCLC.3 Of note, the study presented by Fossella et al1 does not reveal any statistical differences in terms of survival data among the regimens. (2) Concerning the toxicity profile and the impact on the QoL, I will resume my comment on the DOC plus CDDP (DC) versus VC arm, because it seems inappropriate to me to compare a CDDP to a carboplatin-based regimen in this regard. Thus, looking at the grade 3-4 toxicity data, one can notice that statistical significant differences between the arms were recorded in case of nausea, vomiting, and anemia. It is worthy to note that those peculiar toxicities are characteristic to CDDP and not to VNR. From this point of view, the two regimens are not equivalent (75 mg/m2 CDDP in the DC arm compared with 100 mg/m2 in the VC arm). Some retrospective analysis showed that CDDP delivered as 75 to 80 mg/m2 every 3 weeks might have the best therapeutic index, while higher doses add only to the toxic side effects.4 It is plausible that enhanced CDDP dose per cycle in the VC arm might have induced a higher degree of nausea and vomiting, especially when, according to the study protocol, the authors do not confirm the regular use of 5-hydroxytryptamine-3 antagonists as standard antiemesis intervention while dexamethasone, a potential antiemetic adjuvant, was recommended only in the DOC arm. (3) The weekly schedule for VNR administration in combination with CDDP might not be optimal, since the day 15 dose comes just over the rapid recovery of bone marrow elements, leading to an enhanced hematologic toxicity (including anemia). Scheduling VNR on days 1 and 85 and lowering CDDP at 75 to 80 mg/m2 every 3 weeks would preserve the dose-intensity of the drugs while diminishing the intensity of associated side effects. A recently presented phase III randomized trial confirmed the above-mentioned assumption.6 In fact, a similar pharmacologic interference was noticed for the gemcitabine plus CDDP combination, which led to a change of the original days 1, 8, and 15 schedule to a days 1 and 8 schedule every 3 weeks.7 (4) The QoL evaluation showed a statistical significant difference for EuroQoL (global QoL scale; P = .016) but not for the Lung Cancer Symptom Scale (P = .064), both of them favoring the DC arm. However, it is worthy to note that a lot of bias could be raised concerning the methodology of QoL evaluation, some of which were very elegantly assessed by the reviewers. More details about this aspect were presented recently.8 On the other hand, this negative trend for QoL in the VC regimen would have been expected, while roughly 25% of the patients were recorded with 3-4 grade anemia. Early intervention on this aspect (erythropoietin, transfusions) would have precluded the impact of anemia related symptoms (dyspnea, malaise, anorexia) on the QoL. From this point of view it is worthy to note that two other randomized trials found no difference in the QoL between the same VC schedule compared with other accepted first-line platinum-based doublets (paclitaxel [TXL] or gemcitabine).9,10 (5) Despite the statistical significant difference in the mean weight loss during the treatment, the actual numeric difference (2.06 kg) seems clinically irrelevant. Of note, the grade 1-4 edema was 32% (DC) versus 16% (VC). (6) Last but not least, the cost of the treatment is to be taken into account while evaluating the recommendations for the first-line treatments, in case of same efficacy. From this point of view, the cost of 6 months with VC ($6,400) compares favorably with most of the accepted first-line standards: gemcitabine-CDDP, $10,800, TXL-CDDP, $15,000, or TXL-carboplatin, $24,000.11 Considering the above mentioned aspects, I believe that the VNR plus CDDP combination still has a role to play in the first-line treatment options for advanced NSCLC. Author's Disclosures of Potential Conflicts of Interest The author indicated no potential conflicts of interest. REFERENCES
1. Fossella F, Pereira JR, von Pawel J, et al: Randomized, multinational, phase III study of docetaxel plus platinum combination versus vinorelbine plus cisplatin for advanced non-small cell lung cancer: The TAX 326 study group. J Clin Oncol 21:3016-3024, 2003
2. Harper P, Plunkett T, Khayat D: Quality trials and quality of life in non-small-cell lung cancer. J Clin Oncol 21:3007-3008, 2003 3. Giaccone G: State of the art in systemic treatment of lung cancer. Eur J Cancer 37:S99–S114, 2001 (suppl 7) 4. Raftopoulos H, Gralla R, Nelli F, et al: Can survival be found among cisplatin, carboplatin, and non-platinum regimens? Results of a comprehensive review of chemotherapy in advanced non-small-cell lung cancer (NSCLC) randomized trials including 12,181 patients from 1992-2002. Lung Cancer 41:S68, 2003 (suppl 2; abstr 0-232)
5. The Elderly Lung Cancer Vinorelbine Italian Study Group. Effects of vinorelbine on Quality of life and survival of elderly patients with advanced non-small cell lung cancer. J Natl Cancer Inst 91:66-72, 1999 6. Gebbia V, Galetta D, Caruso M, et al: Phase III trial comparing cisplatin (CDDP) plus weekly vinorelbine (VNR) and CDDP plus day 1+8 VNR in advanced non small cell lung cancer (NSCLC). Lung Cancer 41:S63, 2003 (suppl 2; abstr 0-216) 7. Soto Parra HJ, Cavina R, Antonelli G, et al: Superiority of three-week vs. four-week schedule of cisplatin and gemcitabine: Results of a randomized phase II study. Proc Am Soc Clin Oncol 19:546a, 2000 (abstr 2152) 8. Bottomley A, Efficace F, Thomas R, et al: Health-related quality of life in non-small-cell lung cancer. Methodologic issues in randomized controlled trials. J Clin Oncol 15:2982-2992, 2003
9. Kelly K, Crowley J, Bunn PA, et al: Randomized phase III trial of paclitaxel plus carboplatin versus vinorelbine plus cisplatin in the treatment of patients with advanced non-small cell lung cancer: A Southwest Oncology Group Trial. J Clin Oncol 19:3210-3218, 2001
10. Scagliotti GV, De Marinis F, Rinaldi M, et al: Phase III randomized trial comparing three platinum-based doublets in advanced non-small cell lung cancer. J Clin Oncol 20:4285-4291, 2002 11. Gralla RJ, Grusenmeyer PA, Brooks BJ: Evaluating the costs and cost-effectiveness of new regimens for non-small cell lung cancer (NSCLC). Proc Am Soc Clin Oncol 16:420a, 1997 (abstr 1501)
Related Article
Related Editorial
Related Reply
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|
|
|||||||||||
|
|||||||||||
|
|
Copyright © 2004 by the American Society of Clinical Oncology, Online ISSN: 1527-7755. Print ISSN: 0732-183X
|
