| Combination Therapy Effective
for Locally Advanced Vulvar Cancer ORLANDO — Concurrent radiation and cisplatin therapy is a reasonable standard of care for patients with locally advanced vulvar cancer, researchers reported here at the Society of Gynecologic Oncology meeting. In a Phase II trial of 58 patients given the combination treatment, two-thirds had clinical complete responses and half had pathologic complete responses. Evolving Therapy For years, Stage T3-4 locally advanced vulvar cancer was thought of as a purely surgical disease, said David H. Moore, MD, a specialist in gynecologic oncology at St. Francis Hospital in Indianapolis, noting that the surgery was cumbersome and often necessitated urinary diversion and/or colostomy. In the 1980s, there was a paradigm shift in treatment, with several groups reporting good outcomes with radiation followed by surgery, Dr. Moore said. The combination led to excellent long-term control and high rates of bladder and rectal preservation. The case reports led to the Gynecologic Oncology Group (GOG) 101 trial of concurrent cisplatin and 5-flouraracil (5-FU) chemotherapy plus radiation. In that study, 48% of patients had clinical complete responses, and only 3% of patients needed urinary diversion or colostomy (Int J Radiat Oncol Biol Phys 1998;42:79-85). "There was still room, however, for improvement because still 50% of patients still had residual microscopic disease, and in eight patients, the vulva was the initial site of recurrence," Dr. Moore said. Design Changes That led to the current Phase II GOG 205 trial, which had several important design changes, he said. First, the chemotherapy was changed from cisplatin-5FU to weekly infusions of cisplatin alone, as is used in cervical cancer, Dr. Moore said. The radiation dose of 47.6 Gy in GOG 101 was intentionally low because all patients were expected to undergo surgical resection, said Dr. Moore. In GOG 205, the total dose was increased by 20% to 57.6 Gy in hopes of maximizing the chemotherapy-radiation interaction. Finally, GOG 101 called for twice-daily radiation therapy, and a treatment break between the first and second cycles of therapy -- "a schedule that is detrimental to the patient," he said. In GOG 205, radiation therapy was given once a day, and the treatment break was eliminated. Interim Analysis At the SGO meeting, Dr. Moore reported results of a planned interim analysis of the GOG 205 trial. A total of 29 of the 58 patients (50%) had pathologic complete responses, compared with 22 of the 71 patients (31%) in GOG 101. Additionally, 37 (64%) patients in GOG 205 had clinical complete responses versus 34 (48%) in GOG 101. Overall, 40 of the 58 patients (69%) completed all treatment, Dr. Moore said. The most common toxicities were hematologic adverse events, dermatitis, pain, and metabolic disturbances. "Although there is still considerable room for improvement, the results of GOG 205 indicate that this is a reasonable standard for treatment of locally advanced squamous-cell carcinoma of the vulva and should be the treatment program for future comparisons in prospective trials," Dr. Moore said. Discussant Study discussant Akila N. Viswanathan, MD, MPH, Director of Gynecologic Radiation Oncology at the Dana-Farber Cancer Institute and Associate Professor of Radiation Oncology at Harvard Medical School, said, "The study leaves us with the question of whether weekly cisplatin with concurrent radiation should be the standard of care for locally advanced vulvar cancer." Dr. Moore would not be pinned down however, instead reiterating that "it's a reasonable standard of care." While there have been no randomized controlled trials comparing chemoradiation to radiation alone, Dr. Viswanathan noted that concurrent chemoradiation is associated with a survival benefit in other squamous-cell cancers, including anal and cervical cancer. Dr. Viswanathan also asked Dr. Moore why he thought the GOG 205 regimen was associated with better outcomes than GOG 101. He replied that he did not think that the switch to platinum-only chemotherapy accounted for the improved results. "I do think the escalation of the radiation dose was probably the biggest factor," he said. The elimination of the treatment break may also have played a role, he said. In response to a question from the audience, Dr. Moore said that he could not address long-term toxicities and quality of life. "There is a possibility of doing a downstream follow-up, but that is not inherent to the study design," he said.
Gynecol Oncol. 2012
Mar;124(3):529-33. Epub 2011 Nov 9.
A phase II trial of radiation therapy and weekly cisplatin chemotherapy for the treatment of locally-advanced squamous cell carcinoma of the vulva: a gynecologic oncology group study.SourceGynecologic Oncology of Indiana, Indianapolis, IN 46237, USA. David.Moore@ssfhs.org AbstractOBJECTIVES:To determine the efficacy and toxicity of radiation therapy and concurrent weekly cisplatin chemotherapy in achieving a complete clinical and pathologic response when used for the primary treatment of locally-advanced vulvar carcinoma. METHODS:Patients with locally-advanced (T3 or T4 tumors not amenable to surgical resection via radical vulvectomy), previously untreated squamous cell carcinoma of the vulva were treated with radiation (1.8 Gy daily × 32 fractions=57.6 Gy) plus weekly cisplatin (40 mg/m(2)) followed by surgical resection of residual tumor (or biopsy to confirm complete clinical response). Management of the groin lymph nodes was standardized and was not a statistical endpoint. Primary endpoints were complete clinical and pathologic response rates of the primary vulvar tumor. RESULTS:A planned interim analysis indicated sufficient activity to reopen the study to a second stage of accrual. Among 58 evaluable patients, there were 40 (69%) who completed study treatment. Reasons for prematurely discontinuing treatment included: patient refusal (N=4), toxicity (N=9), death (N=2), other (N=3). There were 37 patients with a complete clinical response (37/58; 64%). Among these women there were 34 who underwent surgical biopsy and 29 (78%) who also had a complete pathological response. Common adverse effects included leukopenia, pain, radiation dermatitis, pain, or metabolic changes. CONCLUSIONS:This combination of radiation therapy plus weekly cisplatin successfully yielded high complete clinical and pathologic response rates with acceptable toxicity.
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