Effective palliative radiation therapy in advanced and recurrent ovarian carcinoma

Abstract

Purpose: To retrospectively review our experience using radiation therapy as a palliative treatment in ovarian carcinoma.

Methods and Materials: Eighty patients who received radiation therapy for ovarian carcinoma between 1983 and 1998 were reviewed. The indications for radiation therapy, radiation therapy techniques, details, tolerance, and response were recorded. A complete response required complete resolution of the patient’s symptoms, radiographic findings, palpable mass, or CA-125 level. A partial response required at least 50% resolution of these parameters. The actuarial survival rates from initial diagnosis and from the completion of radiation therapy were calculated.

Results: The median age of the patients was 67 years (range 26 to 90 years). A median of one laparotomy was performed before irradiation. Zero to 20 cycles of a platinum-based chemotherapy regimen were delivered before irradiation (median = 6 cycles). The reasons for palliative treatment were: pain (n = 22), mass (n = 23), obstruction of ureter, rectum, esophagus, or stomach (n = 12), a positive second-look laparotomy (n = 9), ascites (n = 8), vaginal bleeding (n = 6), rectal bleeding (n = 1), lymphedema (n = 3), skin involvement (n = 1), or brain metastases with symptoms (n = 11). Some patients received treatment for more than one indication. Treatment was directed to the abdomen or pelvis in 64 patients, to the brain in 11, and to other sites in 5. The overall response rate was 73%. Twenty-eight percent of the patients experienced a complete response of their symptoms, palpable mass, and/or CA-125 level. Forty-five percent had a partial response. Only 11% suffered progressive disease during therapy that required discontinuation of the treatment. Sixteen percent had stable disease. The duration of the responses and stable disease lasted until death except in 10 patients who experienced recurrence of their symptoms between 1 and 21 months (median = 9 months). The 1-, 2-, 3-, and 5-year actuarial survival rates from diagnosis were 89%, 73%, 42%, and 33%, respectively. The survival rates calculated from the completion of radiotherapy were 39%, 27%, 13%, and 10%, respectively. Five percent of patients experienced Grade 3 diarrhea, vomiting, myelosuppression, or fatigue. Fourteen percent of patients experienced Grade 1 or 2 diarrhea, 19% experienced Grade 1 or 2 nausea and vomiting, and 11% had Grade 1 or 2 myelosuppression.

Conclusions: In this series of radiation therapy for advanced ovarian carcinoma, the response, survival, and tolerance rates compare favorably to those reported for current second- and third-line chemotherapy regimens. Cooperative groups should consider evaluating prospectively the use of radiation therapy before nonplatinum and/or nonpaclitaxel chemotherapy in these patients.

Introduction

Ovarian carcinoma is the fifth leading cause of cancer death in women. Although there have been significant advances in treatment, 40 to 85% of patients who have Stage II through IV disease will relapse after primary therapy. In the Gynecologic Oncology Group trial (GOG-111) comparing cis-platinum and cyclophosphamide to cis-platinum and paclitaxel in suboptimally debulked Stage III and Stage IV ovarian carcinoma patients, only 25% remained free of progression at 36 months (1). In GOG-158 which compared the use of carboplatinum and paclitaxel to cis-platinum and paclitaxel in optimally debulked Stage III patients, the median relapse-free survival was only 22 months in both arms (2). Often, depending on the time to relapse, patients may receive additional cycles of platinum or paclitaxel or both with expected response rates between 15% and 35% 3, 4. Salvage surgery may also be invoked.

Second- or third-line chemotherapy is frequently used, but the response rates average between 10% and 26% 5, 6, 7, 8, 9, 10, 11. Disappointingly, such efforts have not been shown to extend survival after relapse (4). Moreover, subsequent failures become progressively less responsive to additional therapy, and the options for treatment quickly become limited. Typically, at this point, palliation of symptoms becomes the utmost priority.

Investigators have examined the use of salvage whole abdominopelvic radiation therapy (WAPRT) after cis-platinum failure or in women who have received more than one salvage chemotherapy regimen 5, 12, 13, 14, 15. The consensus of these investigators is that salvage whole abdomen radiation therapy is minimally effective and too toxic in this situation to recommend. In the United States, radiation therapy is generally the last resort for palliation of severe symptoms. Even for purely palliative treatment, such as control of bleeding or pain, investigators have questioned the utility of radiation therapy in ovarian carcinoma because there may be cross-resistance between cis-platinum and irradiation (16). To complicate the situation further, more recent reports from radiation oncology investigators have proven that this information is not correct and that radiation therapy can be effective after chemotherapy 17, 18, 19. We performed this review to analyze our experience with radiation therapy for ovarian carcinoma over a recent 15-year period and to compare the results with the current literature.