According to phase III trial data presented at the
recent meeting of the American Society of Clinical Oncology (ASCO), a regimen of docetaxel (Taxotere) with cisplatin
(Platinol) yields a significantly better overall survival rate (P = .0469) than
the combination of vinorelbine (Navelbine) and cisplatin in patients with
advanced non-small-cell lung cancer who have not received prior chemotherapy.
Significantly Higher Response Rates
The three-arm study, presented by Chandra P. Belani, MD,
professor of medicine, University of Pittsburgh School of Medicine and
codirector of the Lung Cancer Program at the University of Pittsburgh Cancer
Institute, showed that patients who were treated with docetaxel and cisplatin
survived significantly longer than those who received the combination of
vinorelbine and cisplatina standard regimen for advanced non-small-cell
lung cancer. The median survival for the docetaxel/cisplatin cohort was 10.9
months vs 10 months for the vinorelbine/cisplatin cohort. The 1- and 2-year
survival rates were 46% and 20% vs 42% and 14%, respectively.
"While platinum-based chemotherapy is often viewed as a
first-line therapy for patients with advanced non-small-cell lung cancer,
there is no established treatment standard for this population," said Dr.
Belani. "The improved survival associated with the docetaxel/cisplatin
combination means that a superior treatment may be available for this vast group
of patients who are not candidates for surgical resection."
The overall survival for patients treated with docetaxel and
carboplatin was similar to that of patients treated with vinorelbine and
cisplatin. Median survival was 9.1 months for the docetaxel/carboplatin regimen.
The 1- and 2-year survival rates were also similar in these two arms (37% and
16%, respectively, for the docetaxel/carboplatin group).
Study Population and Protocol
The trial, which was conducted at 135 sites in 28 countries,
included more than 1,200 men and women 18 years of age or older with
pathologically confirmed, unresectable locally advanced and/or recurrent or
metastatic non-small-cell lung cancer and a Karnofsky performance status of at
least 70%. Recurrent disease was defined as evidence of tumor progression after
surgical or radiation treatment. Patients who received prior treatment with a
biological response modifier or chemotherapy agent were ineligible.
The median age of the study population was 60 years, and most
patients were men. Approximately 67% had stage IV disease, and disease had
spread to at least three other organs in about one-third of patients.
Patients were randomized to one of three treatment groups. The
first group received docetaxel at 75 mg/m2 plus cisplatin at 75 mg/m2, with the
cycle repeated every 21 days. The second group received the combination of
docetaxel at 75 mg/m2, and carboplatin at an area under the concentration-time
curve (AUC) of 6, with treatment repeated every 21 days. The third group
received a combination of vinorelbine at 25 mg/m2/wk and cisplatin at 100
with treatment repeated every 28 days. Patients were treated until there was
evidence of progressive disease or unacceptable adverse events, or until six
cycles had been completed. Treatment response was assessed after every two
All treatment arms were generally well tolerated. Less than 5%
of patients experienced severe sensory neuropathy in both docetaxel treatment
arms. Treatment-related infection, febrile neutropenia, and number of deaths
were also similar between the groups. More patients in the vinorelbine/cisplatin
group experienced severe nausea/vomiting and anemia; however, diarrhea was more
common in patients treated with docetaxel/cisplatin.