Improved QOL With Docetaxel/Platinum Regimens in NSCLC Patients

ORLANDO—The largest prospective evaluation of quality of life (QOL) in chemotherapy-naïve patients with advanced non-small-cell lung cancer (NSCLC) found that first-line treatment with docetaxel (Taxotere) plus a platinum agent achieved better QOL than a standard regimen of vinorelbine (Navelbine) and cisplatin (Platinol).

Richard J. Gralla, MD, professor of medicine, Columbia University College of Physicians & Surgeons, reported the results of TAX 326 at the 38th Annual Meeting of the American Society of Clinical Oncology (abstract 1196).

In short, he said, QOL differences were found among the treatment arms at all treatment cycles favoring the docetaxel/cisplatin and docetaxel/carboplatin (Paraplatin) arms, compared with vinorelbine/cisplatin.

The study included 1,218 patients from 28 countries and 140 institutions. Approximately two thirds of the patients had stage IV disease, and about one third had metastases to at least three organs.

Patients were randomized to one of three treatment arms: Arm A was docetaxel 75 mg/m² plus cisplatin 75 mg/m² every 21 days. Arm B was docetaxel 75 mg/m² plus carboplatin to AUC 6 every 21 days. Arm C was vinorelbine 25
mg/m² on days 1, 8, 15, and 22 plus cisplatin 100 mg/m² on day 1 every 28 days.

The study was designed to compare Arm A and Arm B, respectively, with Arm C, which was a standard chemotherapy doublet. Arm A and Arm B were not directly compared with each other, nor was cisplatin compared with carboplatin, Dr. Gralla noted.

The clinical endpoints analysis of TAX 326, previously reported, showed a significant improvement in survival favoring docetaxel/cisplatin (median survival, 11.3 months vs 10.1 months for vinorel-bine/cisplatin, P = .044). Two-year survival was 21% vs 14%, respectively. There was no significant difference in median survival for docetaxel/carboplatin vs vinorelbine/cisplatin.

Grade 3-4 toxicity (nausea, anemia, and vomiting) was more frequent with vinorelbine/cisplatin than in either of the docetaxel-containing arms (P < .01). Neutropenia, infection, and febrile neutropenia were similar for all arms.

Quality of life was assessed in 926 (76%) patients. Assessments were completed before each treatment cycle, at the end of the study, and every other month during follow-up. Two instruments were used: the Lung Cancer Symptom Scale (LCSS), an assessment of serial QOL and symptoms that is completed by the patient as well as the physician or nurse, and the European Organization for the Research and Treatment of Cancer (EORTC) quality of life questionnaire (EQ-5D), which is self-administered and measures health status and adjusted survival.

A trend toward higher rates of compliance was seen in both docetaxel-containing arms vs the vinorelbine/cisplatin arm for the first six treatment cycles. At the sixth cycle, compliance rates were 68% for both docetaxel-containing arms and 53% for vinorelbine/cisplatin.

Compared with vinorelbine/cisplatin, global QOL was better for docetaxel-containing regimens, both for cisplatin (P = .064 on LCSS and .016 on EQ-5D) and carboplatin (P = .016 on LCSS and < .001 on EQ-5D). The change in pain score from baseline favored docetaxel/cisplatin (P = .033). Performance status improved with both docetaxel-containing arms, and weight loss of 10% or more was less frequent in these arms (7% vs 15%; P < .001), Dr. Gralla reported.

"In the two docetaxel arms, you see improvements in quality of life, either of borderline or statistical significance, using two different instruments," Dr. Gralla said. "You also see clinical benefits for pain control, weight loss, and performance status in the docetaxel arm. The magnitude of any of these effects is not huge, but there is improvement."

He said there is a continued need for investigators to recognize the value of QOL in clinical trials. He noted that some investigators elected not to participate in the QOL assessment component of TAX 326. "This trial shows that QOL can be assessed efficiently, with high acceptance by patients and health care professionals, during a large-scale multinational prospective trial when practical and validated instruments are used," he said. "QOL assessment can be a simple and inexpensive part of routine management for patients participating in trials and for those not in studies."