International Journal of Radiation Oncology*Biology*Physics
Clinical InvestigationsAlternating radiotherapy and chemotherapy for inoperable stage III non–small-cell lung cancer: long-term results of two phase II GOTHA trials
Introduction
Locally advanced Stage IIIA and IIIB disease represents about 40% of all currently diagnosed cases of non-small cell lung cancer (NSCLC). Although treatment philosophy toward this disease at this stage varies considerably from country to country (1), conventionally fractionated, moderate- to high-dose radiotherapy (RT) was considered by many as the treatment of choice, since it was shown to have a small but definitive curative potential, with a median survival of 9–12 months 2, 3. With radiotherapy alone, both local and distant failures rates were high; therefore, many studies were conducted in which chemotherapy was added to standard radiotherapy, aiming at improving local and distant control 4, 5, 6. From several randomized Phase III trials, it appeared that only platin-based combinations of chemotherapy (CT) and radiotherapy had an impact on survival 7, 8, 9, 10, 11, 12. In the EORTC trial, daily, low-dose cisplatin with RT demonstrated a significant improvement in local control and survival (12), whereas in the French study, the addition of vindesin, cyclophosphamide, cisplatin, and lomustin, before and after radiotherapy, led to a decrease of distant metastases with an improved survival when compared to RT alone 9, 10. A large number of drug associations and RT-CT combinations have been tested. The majority of published Phase II or III trials deal with sequential CT-RT regimes or concomitant CT-RT regimes; only very few have tried truly alternated RT-CT in NSCLC (13). Our group elected to study the latter type of combination, based on theoretical and practical considerations. According to the Goldie and Coldman mathematical model (14), and experimental animal data (15), a rapid alternance of chemotherapy and radiotherapy may prove efficient by decreasing the emergence of resistant tumor cells to either modality. In addition, rapidly alternating schedules, like concomitant schedules, allow the delivery of RT and CT in a shorter period of time when compared to sequential schemes, while trying to avoid the synchronous additive toxic effect of CT and RT produced by their simultaneous application.
We present here the results of two consecutive Phase II trials, GOTHA I and GOTHA II, in which a total of 132 patients with Stages IIIA and IIIB NSCLC were entered from 1986 to 1992.
Section snippets
Patients and methods
Between February 1986 and September 1989, 65 patients were entered in the first Phase II trial (GOTHA I) (13), and between December 1989 and October 1992, 67 patients were enrolled in the second Phase II trial (GOTHA II). Eligibility criteria, treatment intent, radiotherapy protocols, type of combined chemotherapy-radiotherapy, evaluation parameters, and participating institutions were identical in both studies; the only difference was due to the chemotherapeutic regimes. Since separate
Patients
A total of 132 patients were enrolled by the member institutions of the GOTHA group in these two consecutive Phase II studies: 65 patients in GOTHA I and 67 in GOTHA II. Patients’ overall characteristics are shown in Table 1. When pooling the two studies, the following were included: the median age was 55.5 years, the male to female ratio was 7.3:1, tumor stages were IIIA in 44% and IIIB in 56%, WHO performance status was 0 in 36%, 1 in 52%, and 2 in 12%. Histologic types consisted in squamous
Discussion
For many years, radiotherapy alone was considered in many countries to be the treatment of choice for inoperable Stage III NSCLC, and was shown to have a modest, but definitive curative potential 2, 3, 22. In the last two decades, a large number of Phase II studies have shown that various combinations of chemotherapy and radiation therapy were feasible, with a high degree of activity, and suggested an improved survival. These apparently encouraging results stimulated various institutions or
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