LONDON, UK-Preliminary results of the Big Lung Trial in a supportive care setting found chemotherapy improved survival of patients with non-small-cell lung cancer (NSCLC) without diminishing their quality of life, according to a report presented by R.J. Stephens, MD, representing the CRC and UCL Cancer Trials Centre, London (ASCO abstract 1161).
LONDON, UKPreliminary results of the Big Lung Trial in a supportive care setting found chemotherapy improved survival of patients with non-small-cell lung cancer (NSCLC) without diminishing their quality of life, according to a report presented by R.J. Stephens, MD, representing the CRC and UCL Cancer Trials Centre, London (ASCO abstract 1161).
"The [prior] meta-analysis included many small trials that used different measurements, different eligibility, and gave minimum information about toxicity and treatment-related deaths and no information at all about quality of life or health economics," Dr. Stephens said.
The aim of the Big Lung Trial was to conduct a single large, multicenter, randomized trial to determine the role of short-term cisplatin-based chemotherapy for all patients with NSCLC. Dr. Stephens reported on preliminary results for patients in a supportive care setting.
Broadly Inclusive Study
Investigators decided to be as inclusive as possible. The only eligibility criterion was having been recently diagnosed with NSCLC, at a time that was relatively late to consider chemotherapy or when there was uncertainty on the part of the patient or physician about the value of chemotherapy. Following primary treatment, which could include surgery, radical radiotherapy, or best supportive care, patients were randomized into two cohorts: chemotherapy or no chemotherapy.
"The design also allowed some flexibility in the choice of regimen," Dr. Stephens said. "Initially three regimens commonly used in the UK were permitted. But about half way through the trial, as new drugs became available, there was pressure to increase the choices."
The trial management group developed criteria for types of chemotherapy that would be allowed, such as evidence from a large, randomized trial that the new regimen was at least as good as the ones being used. At that time, NP (vinorelbine [Navelbine]/cisplatin [Platinol]) was added to the three existing regimens, which were CV (cisplatin/vindesine), MIC (mitomycin [Mutamycin]/ifosfamide [Ifex]/cisplatin) and MVP (mitomycin/vinblastine/cisplatin).
"The initial end was to accrue sufficient patients in each of the settings to confirm survival differences seen in the meta-analysis," Dr. Stephens continued. "However, this proved too daunting a task."
After 6 years, the trial was closed. Researchers felt waiting several more years to achieve all the targets was not justified and that it was more important to produce results as soon as possible.
"Nevertheless, the 725 patients in a supportive care setting make this by far and away the largest trial in this setting, with nearly as many patients as were in the meta-analysis and approximately the same number as all subsequent trials put together," Dr. Stephens said.
Sufficient for Analysis
The quality-of-life investigation started late and just missed its target of 300 patients, likely due to a decline in enrollment in the last couple of years. Nevertheless, Dr. Stephens said the 273 accrued135 in the chemotherapy arm and 138 in the no treatment armwere sufficient for analysis.
Chemotherapy was given to 364 patients, and 361 received none. Patients were well balanced between the two arms in terms of baseline characteristics. Ninety-three percent of patients had stage III or IV disease. Elderly stage I or II patients who had poor performance status or refused more radical treatment were included in the study.
Most patients received MIC, MVP, or NP. Sixty-five patients in the chemotherapy arm received three cycles, 48% with no delays or modifications. A few received no chemotherapy due to deterioration or death. A quarter had one or two cycles due to deterioration, toxicity, or patient request. A few patients in the no-chemotherapy arm received chemotherapy due to administrative error or the patient changing his or her mind. All patients remained in the study, because this was an intention-to-treat analysis.
Toxicity occurred as expected, with 29% of chemotherapy recipients experiencing grade 3 or 4 toxicity, mainly hematologic effects, nausea/vomiting, and neutropenic fever. Nearly 5% succumbed to treatment-related deaths. Only 10% of the patients are still alive.
Chemotherapy provided a median survival benefit of about 2 months, a 10% benefit at 1 year and a 4% benefit at 2 years. The survival advantage remained consistent across subgroups.
The quality-of-life analysis showed very little difference between the two groups. Evaluation of health service costs determined that, apart from chemotherapy patients incurring drug and related hospitalization expenditures, all other costs were similar.