Few Long-Term SCLC Survivors With Current Rx

CHICAGO—Although concomitant platinum-based systemic chemotherapy and thoracic radiotherapy have yielded the best short-term survival rates for patients with limited-stage small-cell lung cancer (SCLC), this approach produces few long-term survivors because local failure and distant metastasis are common.

That is why Charles R. Thomas, Jr, MD, suggested that oncologists encourage patients who reach the 2-year mark after current treatment to participate in chemoprevention studies involving novel antiproliferative systemic agents directed at inhibiting tumor growth and retarding disease progression. Dr. Thomas is a radiation and medical oncologist at the University of Texas Health Science Center at San Antonio/San Antonio Cancer Institute and a member of the Southwest Oncology Group (SWOG).

Long-Term Results of SWOG 8269

In a presentation at the annual meeting of the Radiological Society of North America (RSNA), Dr. Thomas reported the long-term results from SWOG 8269, the first North American cooperative experience with concomitant cisplatin (Platinol), etoposide (VePesid), and external beam radiation therapy for limited-stage SCLC. Preliminary results of the trial had been published previously after a follow-up period of 3 years, and a further analysis of data concerning patterns of failure was performed after a median follow-up period of 6.5 years.

Because of recent observations in the literature about long-term survival of patients with limited-stage small-cell lung cancer, SWOG again reviewed data after a minimum follow-up interval of 13.1 years, maximum interval of 14.5 years, and median interval of 13.4 years, and Dr. Thomas reported on these findings.

When SWOG 8269 began, it enrolled 123 patients between April 1985 and May 1986. After excluding nine patients, the trial evaluated 114 patients from 47 institutions who received induction chemotherapy, consolidative chemotherapy, and thoracic irradiation.

Therapy Protocol

Induction therapy consisted of three cycles of IV cisplatin 50 mg/m² on days 1 and 8, 29 and 36, and 57 and 64; IV etoposide 50 mg/m² on days 1 through 5, 29 through 33, and 57 through 61; and IV vincristine 1.4 mg/m² on days 15, 22, 43, and 50. Consolidative chemotherapy involved two cycles of vincristine, methotrexate, etoposide, doxorubicin, and cyclophosphamide (Cytoxan, Neosar).

A total thoracic irradiation dose of 45 Gy was administered concomitantly in 25 daily fractions at 1.8 Gy per fraction. A total cranial irradiation dose of 30 Gy was administered in 15 fractions at 2.0 Gy per fraction with the third cycle of chemotherapy.

As of May 2000, 5 of the 114 patients (4%) were alive and free from disease progression. The median progression-free survival was 12 months, and overall survival was 19.5 months. After 2 years, approximately one third of patients were progression free, but by 5 years, only one fourth of patients had no signs of disease progression. Two fifths of patients were alive at the end of 2 years, but only one fourth were alive at the end of 5 years.

Second Primary Cancers

A significant subset of patients developed second primary cancers. Second primary cancers were responsible for the deaths of 29% of 38 patients who died of causes other than small-cell lung cancer.

Second primary cancer tumor types included acute myelogenous leukemia (AML), squamous cell lung cancer, breast cancer, prostate cancer, pancreatic cancer, renal cell carcinoma, and myelodysplasia. One patient had both melanoma and non-Hodgkin’s lymphoma.

A pattern-of-failure analysis involving 76 patients who died of SCLC revealed that local recurrence was a factor in nearly half. Exclusively local failure occurred in one quarter of patients; distant metastasis was the first sign of treatment failure in more than one third of patients; both local and distant failure occurred in approximately one quarter.

Late failures were detected up to 13 years after treatment. Both progression-free and overall survival curves continued to flatten after 12 years, indicating that the risk for late failure or a second malignancy follows survivors well into the second decade after therapy, he said.

Data from SWOG 8269 appear to suggest that progression of SCLC accounts for most of the failures and deaths during the first 3 years after treatment. The cause of treatment failure in subsequent years is not as clear because of confounding variables, such as continued use of tobacco products and upper airway or digestive tract malignancies, he said.

Dr. Thomas indicated that because the survival and disease-free progression curves continue to decline with long-term follow-up, "it would make sense to develop clinical trials to study the effect of maintenance or prophylactic novel anti-proliferative systemic agents because classic cytotoxic chemotherapy and concomitant radiation therapy alone is not going to be the answer."