Hyperthermic Intraperitoneal Chemotherapy in Ovarian Cancer.

Hyperthermic intraperitoneal chemotherapy (HIPEC) is a treatment modality that aims to target the main site of tumor dissemination in ovarian cancer, the peritoneum, by combining the benefits of intraperitoneal chemotherapy with the synergistic effects of hyperthermia all during a single administration at the time of cytoreductive surgery. High-quality evidence currently only supports the use of HIPEC with cisplatin at the time of interval cytoreduction after neoadjuvant chemotherapy for stage III epithelial ovarian cancer. Many questions remain, including HIPEC's role at other timepoints in ovarian cancer treatment, who are optimal candidates, and specifics of HIPEC protocols. This article reviews the history of normothermic and hyperthermic intraperitoneal chemotherapy in ovarian cancer and evidence regarding HIPEC implementation and patient outcomes. Additionally, this review explores details of HIPEC technique and perioperative care, cost considerations, complication and quality of life data, disparities in HIPEC use, and unresolved issues.

Neoadjuvant and adjuvant chemotherapy of cervical cancer: mature results of the phase 2 PBM-PFU protocol.

OBJECTIVE: The mature results of the neoadjuvant and adjuvant chemotherapy arms of the nonrandomized, phase 2 Yale University cisplatin, bleomycin, methotrexate, and 5-FU protocol are presented. METHODS: Sixty-seven patients were prospectively accrued with a median follow-up of 5.4 years, and standard parameters of toxicity and efficacy were studied. Both univariate and multivariate analyses were applied. RESULTS: The 5-year disease-free survival of 78% for the 25 patients in the adjuvant group, of which 80% had high-risk features including positive margins, parametria, and lymph nodes and 28% had adenocarcinomas, was comparable to recent relevant literature. Only 64% of patients in this group received consolidation radiation therapy, which did not impact on survival. Only 12% of patients recurred distantly. Notably, those who received 4 months or more of chemotherapy had prolonged survival (P = 0.012). In the neoadjuvant group, chemotherapy response rate among 42 patients (with stages 1B-IIIB cancer) was 79% (50% partial response, 29% complete response), and no patient progressed. In the subgroup of 22 patients who underwent surgery after chemotherapy, 59% had nonsquamous histology. Forty-five percent of patients with stage IIB cancer were deemed operable after chemotherapy. Ninety-five percent received postoperative radiation therapy. There was a 9% pathologic complete response rate, with positive lymph nodes found in 27%. Notably, those who received 3 months or less of chemotherapy had improved overall survival (P = 0.030). Survival rates of these 22 patients at 3 and 5 years were 73% and 63%, respectively. Although not randomized, these survival rates were similar to those achieved with chemoradiation. CONCLUSIONS: Although there are several logistical/design features of the cisplatin, bleomycin, methotrexate, and 5-FU regimen that are not in line with the current chemotherapy era, our experience with this well-tolerated regimen can serve as a proof of principle. Our data suggests that both neoadjuvant and adjuvant cisplatin-based neoadjuvant chemotherapy may have their place. It also raises the possibility that the optimal duration of chemotherapy in adjuvant cases should be longer than in neoadjuvant cases.

Chemoradiation with 5-fluorouracil and mitomycin C in the treatment of vulvar squamous cell carcinoma.

OBJECTIVE: To investigate the acute and late toxicities associated with the use of chemoradiation therapy (CRT) with 5-fluorouracil (5-FU) and mitomycin C or mitomycin C alone for primary, adjuvant, and salvage therapy for vulvar cancer. METHODS: Medical charts of 17 patients who received CRT with this regimen were reviewed. Toxicity was scored by 1998 standardized common toxicity criteria, Version 2.0, for acute toxicity and the RTOG/EORT Late Radiation Morbidity Scoring Schema for late toxicity. Median follow-up was 20 months (range: 5-74 months). RESULTS: Six patients had grade 4 neutropenia. In three patients, life-threatening neutropenic sepsis developed after the second cycle of chemotherapy. Severe enterocolitis was a direct cause of death in two patients. In four patients, the second cycle of chemotherapy was cancelled because of severe toxicity associated with the first cycle. One patient had grade 4 skin toxicity in the vulvar-perineal area. Six patients had grade 3 and seven patients had grade 2 acute skin toxicity. Skin toxicity necessitated the interruption of CRT in nine patients at a median dose of 32.4 Gy (range: 16.2-48 Gy). One patient developed bowel perforation and colovaginal fistula 1.5 years after completion of CRT. CONCLUSION: Chemoradiation therapy utilizing 5-FU and mitomycin C or mitomycin C alone in the treatment of vulvar cancer can be associated with a high incidence of morbidity and mortality. Strict attention to indications for treatment interruptions or chemotherapy dose adjustments is obligatory for safe delivery of CRT to these patients.