Multidisciplinary Approach to Potentially Curable Non-Small Cell Carcinoma of the Lung

The treatment of potentially curable non-small-cell lung cancer (NSCLC)is currently evolving. Drs. Greco and Hainsworth provide information aboutthe potential use of chemotherapy, radiation, and surgery in patients withstage IB-IV NSCLC. The authors have taken on the challenging task of summarizingrecent clinical research, referencing current clinical studies, and providingsome predictions on the outcomes of ongoing clinical investigation.

Substaging of Stage IIIA Disease

The authors propose that we adopt a staging system for stage IIIA patientswith seven different substages, and they reference Dr. Ruckdeschel's 1996American Society of Clinical Oncology educational session text, which usedfour substages. Although I agree with the concept that investigators needto be accurate in defining the subgroups of patients with stage III NSCLCwho are eligible for different clinical trials and treatment, I believethat substaging of stage IIIA into seven different substages is less attractivethan using careful definitions of those patients eligible for therapeuticinterventions. I think breaking down a subset of stage III (IIIA) intoseven different substages is needlessly complicated and is unlikely tobe adopted by the oncologic community.

Adjuvant, Neoadjuvant, and Concurrent Chemotherapy

The authors present information on neoadjuvant, adjuvant, and concurrenttherapy for patients with stage II and III NSCLC. I agree with their statementsand would like to provide a reference for the published meta-analysis coveringthese topics prepared by the Non-Small Cell Lung Cancer Collaborative Group.[1]This publication provides references for some of the older studies andmay prove more useful to the reader than the abstract reference providedby Greco and Hainsworth (their reference 58).

I also agree with the authors' assessment of the ongoing large NationalCancer Institute (NCI) intergroup study looking at the role of surgicalresection in addition to chemotherapy and chest irradiation in patientswith stage IIIa NSCLC. However, they make the statement, "given allthe data and the several large series reported, we agree with the use ofcombined radiation and chemotherapy in this setting, as well as in theadjuvant setting, for stage II and IIIa patients who are initially resected."I do not concur that there is enough information available to routinelyuse combined-modality therapy after resection in stage II and IIIa patients.The statement is also somewhat at odds with an earlier comment made bythe authors in their discussion of postoperative or adjuvant therapy: "Thereare too few definitive comparisons of therapy to make confident conclusionswith regard to patients who have had surgical resection for stage II andIII disease."

Chemotherapy

I agree with the authors' statements and table about the different generationsof chemotherapy; these provide a useful framework for thinking about currentcombinations of chemotherapy for NSCLC.[1] The authors state that the combinationof paclitaxel (Taxol) and cisplatin (Platinol) has been shown to prolongsurvival, when compared with the older combination of etoposide (Etophos,VePesid)and cisplatin for a patient with advanced NSCLC. They could also have includedthe randomized study showing that patients with stage III or IV NSCLC treatedwith a third-generation combination (vinorelbine [Navelbine] plus cisplatin)lived longer than patients treated with the older standard treatment, vindesine(Eldisine) plus cisplatin.[2] I agree that, taken together, these studiesindicate that third-generation combinations are somewhat more effectivefor patients with advanced NSCLC.

Conclusions

The authors provide a series of recommendations by stage for patientswith NSCLC and employ what they call a positive treatment philosophy andapproach. I think that all of their recommendations have merit and areimportant areas of ongoing clinical research. However, I do not believethat there are adequate data at this time to recommend chemotherapy forpatients with stage Ib disease, and I am particularly concerned about givingcombined-modality therapy to patients with N1 disease in the absence ofdata to support this approach. I am also concerned about recommending thevinorelbine-cisplatin or paclitaxel-carboplatin (Paraplatin) regimens forcombined-modality therapy without information about the efficacy and potentialunanticipated toxicities encountered when combining new drugs with chestirradiation. Unexpected toxicity has been reported this year when paclitaxelwas given weekly with up to 56 Gy of chest radiotherapy.[3] Moderate tosevere interstitial pneumonia developed in 7 of 14 patients.

This article by Drs. Greco and Hainsworth points out important areasin which the treatment for lung cancer is rapidly changing. I agree withmany of their conclusions, but take exception with others, as outlinedabove. The authors and I have a healthy difference of opinion about thecurrent management of NSCLC, but we share optimism about the likelihoodfor some improvement in treatment with the third generation of chemotherapyregimens.

References:

1. Non-Small Cell Lung Cancer Collaborative Group: Chemotherapy in non-smallcell lung cancer: A meta-analysis using updated data on individual patientsfrom 52 randomized clinical trials. Br Med J 311:899-909, 1995.

2. Le Chevalier T, Brisgand D, Douillard JY, et al: Randomized studyof vinorelbine and cisplatin versus vindesine and cisplatin versus vinorelbinealone in advanced non-small cell lung cancer: Results of a European multicentertrial including 612 patients. J Clin Oncol 12:360-367, 1994.

3. Reckzeh B, Merte H, Pfluger KH, et al: Severe lymphocytopenia andinterstitial pneumonia in patients treated with paclitaxel and simultaneousradiotherapy for non-small cell lung cancer. J Clin Oncol 14:1071-1076,1996.