British Trials Assessing Value of Chemo in Advanced NSCLC

TOKYO, Japan—Large, multicenter trials underway in the United Kingdom are questioning whether chemotherapy is actually worth it for patients with advanced non-small-cell lung cancer (NSCLC), according to Jeremy Steele, MD, of the Division of Hematology, Oncology and Imaging, St. Bartholomew’s Hospital, London.

Some studies are looking at the role of platinum-based and newer agents, while others are exploring the role of hyper-fractionated radiotherapy in stage IIIA/B disease.

"In the UK, many respiratory physicians and patients remain uncertain about the value of chemotherapy in NSCLC," Dr. Steele said at the 9th World Conference on Lung Cancer. Respiratory physicians, who care for most lung cancer patients in the United Kingdom, use chemotherapy in just a small proportion of patients with advanced disease.

The Big Lung Trial

The Big Lung Trial (BLT) is looking at the effect of cisplatin (Platinol)-based regimens in NSCLC at any stage, including advanced disease.

The trial design stems in part from a previous meta-analysis of 52 randomized clinical trials, including more than 9,000 patients. The results showed that cisplatin-based chemotherapy provided a modest survival advantage, particularly when combined with best supportive care or radical radiotherapy (NSCLC Collaborative Group: Br Med J 311:899-909, 1995).

Conducted at 72 UK and 8 international centers, the BLT study specifically includes patients in whom the value of chemotherapy is thought to be marginal. The patients are randomized to one of four chemotherapy regimens or no chemotherapy. All patients in the study receive best supportive care.

The four active treatment regimens, given in three cycles at 21-day intervals, include: vindesine (Eldesine)/cisplatin; vinorelbine (Navelbine)/cisplatin; mitomycin (Mutamycin)/ifosfamide (Ifex)/cisplatin (the MIC regimen); and mitomycin/vinblastine/cisplatin (the MVP regimen).

The study will look not only at endpoints of survival and progression but also at questions of quality of life and health economics.

At the time of the World Conference on Lung Cancer meeting, patient accrual in the best supportive care arm had reached 650 patients, with a target of 800 patients. Recruitment is expected to be completed by the autumn of 2001.

Other Ongoing Trials

Dr. Steele described three other ongoing UK trials of chemotherapy in NSCLC. The London Lung Cancer Group is evaluating gemcitabine (Gemzar) plus carboplatin (Paraplatin) vs the MIC regimen in patients with histologically or cytologically proven stage IIIB/IV disease.

In this randomized, phase III trial to include 387 patients, either therapy is given in four courses at 21-day intervals. Besides common response and toxicity endpoints, quality of life is of special concern. Patients will complete a European Organization for Cancer Research and Treatment (EORTC) quality-of-life questionnaire plus a lung cancer module. Accrual is ongoing.

The CHARTWEL study (Continuous Hyperfractionated Accelerated Radiotherapy With Weekend Leave), in progress, is a phase II evaluation of hyperfractionated radiotherapy following chemotherapy.

Conducted at Mount Vernon Hospital, London, the study is predicated on an earlier trial showing that, for patients with localized, inoperable NSCLC, hyperfractionated radiotherapy provides a survival advantage over conventional radiotherapy (Saunders M et al: Lancet 350:161-165, 1997).

"There exists the exciting possibility that the addition of chemotherapy to hyperfractionated radiotherapy could lead to a further improvement in survival," Dr. Steele said. So far, however, only limited data exist on the tolerability and efficacy of the particular combination being used in the study: three cycles of paclitaxel (Taxol)/carboplatin followed by radiation.

Another study to watch asks whether synthetic erythropoietin (epoetin alfa, Epogen, Procrit) will affect survival and quality of life in stage IIIB/IV disease with respect to anemia. The randomized phase III study will require 448 patients, all undergoing cisplatin-based therapy with or without epoetin alfa, to demonstrate a difference in anemia-related quality of life, hemoglobin response, and survival.

Epoetin alfa is administered at 10,000 IU subcutaneously three times a week, starting at onset of anemia and continuing to approximately 1 month after therapy ends.

"This study, now in progress, should help determine the role of this novel agent in reducing the toxicity of chemotherapy," Dr. Steele said.