The treatment of potentially curable non-small-cell lung cancer (NSCLC) is currently evolving. Drs. Greco and Hainsworth provide information about the potential use of chemotherapy, radiation, and surgery in patients with stage IB-IV NSCLC. The authors have taken on the challenging task of summarizing recent clinical research, referencing current clinical studies, and providing some 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 patients with seven different substages, and they reference Dr. Ruckdeschel's 1996 American Society of Clinical Oncology educational session text, which used four substages. Although I agree with the concept that investigators need to be accurate in defining the subgroups of patients with stage III NSCLC who are eligible for different clinical trials and treatment, I believe that substaging of stage IIIA into seven different substages is less attractive than using careful definitions of those patients eligible for therapeutic interventions. I think breaking down a subset of stage III (IIIA) into seven different substages is needlessly complicated and is unlikely to be adopted by the oncologic community.
Adjuvant, Neoadjuvant, and Concurrent Chemotherapy
The authors present information on neoadjuvant, adjuvant, and concurrent therapy for patients with stage II and III NSCLC. I agree with their statements and would like to provide a reference for the published meta-analysis covering these topics prepared by the Non-Small Cell Lung Cancer Collaborative Group. This publication provides references for some of the older studies and may prove more useful to the reader than the abstract reference provided by Greco and Hainsworth (their reference 58).
I also agree with the authors' assessment of the ongoing large National Cancer Institute (NCI) intergroup study looking at the role of surgical resection in addition to chemotherapy and chest irradiation in patients with stage IIIa NSCLC. However, they make the statement, "given all the data and the several large series reported, we agree with the use of combined radiation and chemotherapy in this setting, as well as in the adjuvant setting, for stage II and IIIa patients who are initially resected." I do not concur that there is enough information available to routinely use combined-modality therapy after resection in stage II and IIIa patients. The statement is also somewhat at odds with an earlier comment made by the authors in their discussion of postoperative or adjuvant therapy: "There are too few definitive comparisons of therapy to make confident conclusions with regard to patients who have had surgical resection for stage II and III disease."
I agree with the authors' statements and table about the different generations of chemotherapy; these provide a useful framework for thinking about current combinations of chemotherapy for NSCLC. The authors state that the combination of paclitaxel(Drug information on paclitaxel) (Taxol) and cisplatin(Drug information on cisplatin) (Platinol) has been shown to prolong survival, when compared with the older combination of etoposide(Drug information on etoposide) (Etophos,VePesid) and cisplatin for a patient with advanced NSCLC. They could also have included the randomized study showing that patients with stage III or IV NSCLC treated with a third-generation combination (vinorelbine [Navelbine] plus cisplatin) lived longer than patients treated with the older standard treatment, vindesine(Drug information on vindesine) (Eldisine) plus cisplatin. I agree that, taken together, these studies indicate that third-generation combinations are somewhat more effective for patients with advanced NSCLC.
The authors provide a series of recommendations by stage for patients with NSCLC and employ what they call a positive treatment philosophy and approach. I think that all of their recommendations have merit and are important areas of ongoing clinical research. However, I do not believe that there are adequate data at this time to recommend chemotherapy for patients with stage Ib disease, and I am particularly concerned about giving combined-modality therapy to patients with N1 disease in the absence of data to support this approach. I am also concerned about recommending the vinorelbine-cisplatin or paclitaxel-carboplatin (Paraplatin) regimens for combined-modality therapy without information about the efficacy and potential unanticipated toxicities encountered when combining new drugs with chest irradiation. Unexpected toxicity has been reported this year when paclitaxel was given weekly with up to 56 Gy of chest radiotherapy. Moderate to severe interstitial pneumonia developed in 7 of 14 patients.
This article by Drs. Greco and Hainsworth points out important areas in which the treatment for lung cancer is rapidly changing. I agree with many of their conclusions, but take exception with others, as outlined above. The authors and I have a healthy difference of opinion about the current management of NSCLC, but we share optimism about the likelihood for some improvement in treatment with the third generation of chemotherapy regimens.