A.J. Dembo

Concurrent radiation and chemotherapy in vulvar carcinoma

Between June 1984 and February 1988 the role of radiation with concurrent infusional 5-fluorouracil with or without mitomycin C (CT-RT) was examined in 33 patients with vulvar cancer. The median duration of follow-up is 16 months (range 5 to 45 months). Nine received adjuvant postsurgical CT-RT and none has relapsed in the radiation field. Seven are alive disease free. Two have died of distant metastases. Of the 9 receiving definitive primary CT-RT, 6 had initial complete response with subsequent vulvar relapse developing in 3. Seven of the 9 remain disease free after CT-RT alone (in 3) or with the addition of a local excision of residual or recurrent disease (in 6). One patient did not respond to CT-RT and required a radical vulvectomy and groin node dissection. Fifteen received CT-RT for disease recurrence following primary surgery. Disease was present in the vulva only in 11, vulva and inguinal nodes in 1 and nodes only in 3. Eight of the 15 had a complete response and no relapses occurred in the treated sites. Four of the 8 dying of disease developed pulmonary metastases. Serious late complications developed in 2 patients, 1 avascular hip necrosis and 1 proctitis requiring a defunctioning colostomy. CT-RT appears tolerable and may contribute to enhanced locoregional control in recurrent or advanced disease. As initial therapy it may allow lesser surgery with preservation of normal anatomy in selected primary vulvar cancers.

Concurrent chemoradiation in advanced cervical cancer

The pelvis is the predominant site of failure following radical radiotherapy (RT) for locally advanced cervical cancer. We report the results of phase I-II studies on 200 patients with bulky (greater than or equal to 5 cm) carcinoma of the cervix. Patients were treated between 1981 and 1988 on sequential protocols of concurrent chemoradiation to establish an acceptable treatment regimen. RT with daily or partially hyperfractionated pelvic (n = 154) or pelvic plus paraaortic (n = 46) fields was given by continuous (n = 154) or split course (n = 46) regimens. Infusional fluorouracil (5-FU) in a dose of 1 g/m2/day was given on the first and last 4 days of a 5-week course of continuous RT, or with both halves of split course RT. Seventy-eight patients received bolus mitomycin C (Mit-C), 6 mg/m2, once or twice with the start of the 5-FU infusion. The median external RT dose was 46 Gy (range 40 to 65 Gy) followed in 90% (n = 181) by a single intracavitary application of 40 Gy using a linear source of cesium-137. Median follow up is 2.5 years (range 0.6 to 6.9 years) and is sufficient to reliably estimate late toxicities. Acute toxicities were transient oral mucositis (13), RT interruption for enteritis (7), febrile neutropenia (3), and thrombocytopenic tumor bleed (1). Serious late toxicities resulted in death in 3 patients and occurred in bladder in 6 and in bowel in 25, including 8 patients with tumor recurrence. The incidence of late bowel toxicity correlated with the specific therapy given and decreased with each successive protocol. On logistic regression the only treatment variable showing a statistically significant effect on complications was the use of Mit-C (P = 0.0053). Pelvic RT and 5-FU alone produced fewer complications, only 4/105, than historically seen with standard pelvic RT alone. Three-year pelvic control and survival rates were 85 and 71% respectively in stage Ib/II (n = 100) and 50 and 42% in stage III/IV (n = 100). Encouraged by these results and decreased toxicity, we have begun a phase III study to determine whether the addition of concurrent 5-FU to continuous partially hyperfractionated pelvic RT improves local control and survival.

Changing concepts in the management of vulvar cancer

Vulvar carcinoma varies widely in its clinical presentations and prognosis. The reviewed literature outlines the achievements of conventional surgery, radiation, or chemoradiation therapy in its management. Currently therapeutic concepts are evolving. New treatment strategies replacing the uniform use of radical vulvectomy and bilateral groin dissection are proposed. These strategies are tailored to the clinical and pathological disease extent and location and integrate the possible therapeutic advantages of both surgery and chemoradiation. The testing and use of the proposed multimodality therapy protocols require the expertise of gynecologic, radiation, and medical oncologists. This approach should lead to improved anatomic and functional preservation in early disease and improved locoregional in advanced disease.

Concurrent radiation and chemotherapy for carcinoma of the cervix recurrent after radical surgery

Results of salvage therapy in patients with carcinoma of the cervix, recurrent after primary surgery, have been dismal even when disease was apparently confined to the pelvis. Further surgery or radiation therapy cured only some with central pelvic disease alone who had recurred at intervals longer than 6 months after primary therapy. To try to improve the results of salvage therapy, we used a combination of concurrent chemotherapy, 5-Fluorouracil with or without Mitomycin-C, and radiation therapy. Seventeen patients were treated. Recurrent disease was present in the pelvis or pelvis and paraaortic nodes after radical surgery for Stage IB carcinoma of the cervix. Eight of seventeen (47%) are alive, disease-free, 21 to 58 months after therapy. Seven of the eight had biopsy proven recurrence. Five of eight had recurred within 9 months of primary surgery and 7/8 had a component of pelvic side wall disease. Thus the survivors had unfavorable prognostic features. Nevertheless, the use of concurrent radiation and chemotherapy produced an exceptionally high proportion of sustained complete remissions and possible cures.

Outcome of patients with unfavorable optimally cytoreduced ovarian cancer treated with chemotherapy and whole abdominal radiation

There is a subgroup of patients with Stage II or III ovarian cancer whose survival is poor despite optimal cytoreduction of tumor and abdominopelvic radiation. This study examined whether the survival of these patients, who have tumor with unfavorable histopathological characteristics and/or small residual disease, could be improved by giving chemotherapy before radiation. Forty-four out of fifty-one eligible patients, seen between 1981 and 1985, with Stage II or III disease were entered into the study. Following six courses of cisplatin-based chemotherapy, 33 (75%) received abdominopelvic radiotherapy. Survival was compared to that of 48 eligible matched control patients, treated with radiation between 1978 and 1981. The median follow-up is 6.6 years. The median survival was extended from 2.4 to 5.7 years (P = 0.13), and 42.6% of patients receiving combined therapy were free of relapse at 5 years, compared to 21.6% (P = 0.03) in the historical control group, treated with abdominopelvic irradiation alone. Only 2 of 44 patients in the combined group required surgery for bowel obstruction, as did 1 of 48 in the control group. Tolerance and toxicity of the combined approach were acceptable. Although we cannot be certain that the entire benefit we observed was not attributable to the chemotherapy alone, there is evidence that the radiotherapy may have been additive. Chemotherapy followed by abdominopelvic radiotherapy seems a reasonable management policy in these patients.