Preoperative chemo-radiation for carcinoma of the vulva with N2/N3 nodes: a gynecologic oncology group study.

Montana GS, Thomas GM, Moore DH, Saxer A, Mangan CE, Lentz SS, Averette HE

Purpose: To determine if patients with carcinoma of the vulva, with N2/N3 lymph nodes, could undergo resection of the lymph nodes and primary tumor following preoperative chemo-radiation.Methods and Materials: Fifty-two patients were entered in the study, but six patients did not meet the criteria of the protocol and were excluded. The remaining 46 patients are the subject of this report. Patients underwent a split course of radiation, 4760 cGy to the primary and lymph nodes, with concurrent chemotherapy, cisplatin/5-FU, followed by surgery.Following chemo-radiation, the disease in the lymph nodes became resectable in 38/40 patients. The specimen of the lymph nodes was histologically negative in 15/37 patients. Nineteen patients developed recurrent and/or metastatic disease. The sites of failure were as follows: primary area only, 9; lymph node area only, 1; primary area and distant metastasis, 1; distant metastasis only, 8. Local control of the disease in the lymph nodes was achieved in 36/37 and in the primary area in 29/38 of the patients. Twenty patients are alive and disease-free, and five have expired without evidence of recurrence or metastasis. Two patients died of treatment-related complications. Conclusion: High resectability and local control rates of the lymph nodes were obtained in patients with carcinoma of the vulva with N2/N3 nodes treated preoperatively with chemo-radiation.

Int J Radiat Oncol Biol Phys 1998 Aug 1;42(1):79-85

Preoperative chemoradiation for advanced vulvar cancer: a phase II study of the Gynecologic Oncology Group.

Moore Seventy-three evaluable patients with clinical Stage III-IV squamous cell vulvar carcinoma were enrolled in this prospective, multi-institutional trial. Treatment consisted of a planned split course of concurrent cisplatin/5-fluorouracil and radiation therapy followed by surgical excision of the residual primary tumor plus bilateral inguinal-femoral lymph node dissection. Radiation therapy was delivered to the primary tumor volume via anterior-posterior-posterior-anterior (AP-PA) fields in 170-cGy fractions to a dose of 4760 cGy. Patients with inoperable groin nodes received chemoradiation to the primary vulvar tumor, inguinal-femoral and lower pelvic lymph nodes. Following chemoradiotherapy, 33/71 (46.5%) patients had no visible vulvar cancer at the time of planned surgery and 38/71 (53.5%) had gross residual cancer at the time of operation. Using this strategy of preoperative, split-course, twice-daily radiation combined with cisplatin plus 5-fluorouracil chemotherapy, only 2/71 (2.8%) had residual unresectable disease. In only three patients was it not possible to preserve urinary and/or gastrointestinal continence.

Gynecol Oncol 1997 Aug;66(2):258-61

Primary radiation, cisplatin, and 5-fluorouracil for advanced squamous carcinoma of the vulva.

Cunningham. 14 patients with primary squamous carcinoma of the vulva who were not candidates for standard radical vulvectomy were treated with radiation therapy in combination with cisplatin and 5-fluorouracil (5-FU) chemotherapy at the Albany Medical Center. Treatment included two cycles of chemotherapy with cisplatin (50 mg/m2) and 5-FU (1000 mg/m2/24 x 96 hr) in addition to radiation therapy. Total radiation doses to the vulva and groins ranged from 50 to 65 Gray (Gy), with pelvic doses of 45 to 50 Gy. Surgical excision of the primary site was not performed in patients who had complete clinical response. There was a 92% response rate with complete responses in 9 patients (64%). Among patients with complete clinical response, there has been only one recurrence with follow-up of 7-81 months, mean 36.5. All patients with partial responses died, with survival of 8-25 months, mean 15.7. CONCLUSIONS: This combination of chemoradiation was found to be effective therapy for locally advanced vulvar carcinoma, with acceptable morbidity even in an elderly population. Surgical excision of the primary site is not necessary in patients with complete response.

Gynecol Oncol 1996 Jun;61(3):321-7

Concurrent preoperative chemotherapy with 5-fluorouracil and mitomycin C and radiotherapy (FUMIR) followed by limited surgery in locally advanced and recurrent vulvar carcinoma.

Landoni University of Milan, Italy. 58 patients referring for primary (41) or recurrent (17) disease received preoperative external radiotherapy to a dose of 54 Gy, divided into two courses with an interval of 2 weeks. 5-Fluorouracil (750 mg/m2 daily for 5 days) and mitomycin-C (15 mg/m2 single bolus) were given at the start of each cycle. Wide local excision and inguinal lymphadenectomy were planned after treatment. Eighty-nine percent of patients completed the chemoradiotherapeutic treatment, whereas 72% underwent surgery. Objective responses were observed in 80% of vulvar diseases and in 79% of groin metastases. This treatment allows good control of locally advanced and recurrent vulvar cancer with acceptable side effects.

Gynecol Oncol 1995 Oct;59(1):51-6

Prolonged continuous infusion cisplatin and 5-fluorouracil with radiation for locally advanced carcinoma of the vulva.

Eifel M.D. Anderson Cancer Center,. Twelve patients ages with locoregionally advanced vulvar carcinoma were treated with a combination of irradiation and chemotherapy using prolonged continuous infusions of 5-fluorouracil (5-FU) and cisplatin. Patients received weekly 96-hr infusions of cisplatin (4 mg/m2/day) and 5-FU (250 mg/m2/day) for a total of 64 mg/m2 of cisplatin and 4 g/m2 of 5-FU in 4 weeks. Concurrent radiation therapy was delivered to the lower pelvis, vulva, and inguinal nodes to a total dose of 40-50 Gy at 2 Gy per fraction in 11 patients.Eleven of 12 patients had at least a partial clinical response; one patient had a minimal response of unresectable vulvar disease. Overall, 6 of 12 patients treated with this chemoradiation regimen remain disease-free 17-30 months after treatment. This is a well-tolerated outpatient regimen that yields a high response rate in patients with massive vulvar carcinomas.

Int J Radiat Oncol Biol Phys 1993 Aug 1;26(5):809-16

Combined radiotherapy and chemotherapy in the management of local-regionally advanced vulvar cancer.

Koh University of Washington . 20 patients with locally extensive primary or recurrent carcinoma of the vulva were treated with initial combined radiotherapy and chemotherapy.Median radiation doses to regions of microscopic disease and gross tumor were 40 Gy (range 30-54 Gy) and 54 Gy (34-70.4 Gy), respectively. All patients received 2 or 3 cycles of 5-Fluorouracil concurrently with radiotherapy. In addition, five patients received Cis-platinum, and one Mitomycin-C. Ten patients had complete resolution of tumor to initial chemoradiotherapy, and eight of these have remained free of tumor relapse. Eight other patients had partial responses, with tumor bulk reduced by > 50%, while the remaining two patients had local-regionally progressive disease. Six of the patients with partial responses had residual tumor successfully resected, although four subsequently recurred. For the entire group of 20 patients, the actuarial 3- and 5-year local control rates were 48% each, and the corresponding disease-specific survival rates were 59% and 49%. There was a suggestion that better local control was obtained in patients who received gross tumor radiation doses > or = 50 Gy. Skin reaction was the major acute toxicity and responded well to conservative management. Long-term sequalae were limited to skin and subcutaneous atrophy.

Gynecol Oncol 1991 Sep;42(3):197-201

Concurrent cisplatin and 5-fluorouracil chemotherapy and radiation therapy for advanced-stage squamous carcinoma of the vulva.

Berek UCLA . trial of concurrent cisplatin and 5-fluorouracil (5-FU) chemotherapy and radiation therapy (CT + RT) was conducted for the primary treatment of 12 patients with retrospective surgical FIGO stages III-IV squamous carcinoma of the vulva. Chemotherapy was used as a radiation sensitizer and it was administered in two 5-day cycles 28 days apart. Cisplatin, 50 mg/m2/day iv on Days 1 and 2 or 100 mg/m2 on Day 1 or 2, plus continuous-infusion 5-FU, 1000 mg/m2/day for 4-5 days commencing on Days 1 and 28 of external-beam radiation therapy, are given. The pelvic radiation to a dose of 4400-5400 cGy is administered AP and PA to treat the primary tumor, the groin nodes, and the iliac vessels to the level below the common iliac nodes. Complete tumor responses were seen in 8 of 12 (67%) patients. Responses were observed in 6 of 8 (75%) stage III patients and 2 of 4 (50%) stage IV patients. At the completion of concurrent chemoradiation therapy, radical vulvectomy or excision was used in 3 patients and posterior exenteration in 1. With a median follow-up of 37 months (range, 7-60 months), 10 patients are alive and free of disease, and 2 patients died at 12 and 15 months. The morbidity included moist desquamation of the vulva in all patients, with grade 2 toxicity in 10 and grade 3 in 2. These data support the use of concurrent cisplatin and 5-FU chemotherapy and radiation therapy as an alternative to primary radical surgery to treat advanced-stage squamous carcinoma of the vulva.