Phase II study of concomitant chemoradiotherapy with local hyperthermia and metronidazole for locally advanced fixed rectal cancer

Abstract

Aim Locally advanced fixed T4 rectal cancer has a poor prognosis and no standard treatment strategy. The aim of this study was to investigate the safety and efficacy of neoadjuvant chemoradiotherapy using hypofractionated radiotherapy combined with local hyperthermia, capecitabine, oxaliplatin and metronidazole.Method Radiotherapy was given to a total dose of 40 Gy in 10 fractions. Capecitabine 650 mg/m 2 twice a day was given on days 1À22 and intravenous oxaliplatin 50 mg/m 2 was administered on days 3, 10 and 17. Local hyperthermia, 41À45°C for 60 min, was performed on days 8, 10, 15 and 17. Metronidazole 10 g/m 2 was administered per rectum on days 8 and 15. Surgery was carried out within 6À8 weeks after neoadjuvant treatment. The primary end-point was R0 resection rate. Secondary end-points included 2-year disease-free survival, 2-year overall survival, local recurrence rate, grade IIIÀIV tumour regression (Dworak) and treatment toxicity.Results From July 2006 to February 2011, 64 previously untreated patients were enrolled. R0 resection was carried out in 59 (92.2%). Five (7.8%) remained inoperable. Seven (10.9%) patients had grade IV and 30 (46.9%) had grade III regression. The main grade III toxic events included diarrhoea (15.6%, n = 10), vomiting (3.1%, n = 2), proctitis (3.1%, n = 2) and skin reaction (1.6%, n = 1). Only one (1.6%) patient had grade IV diarrhoea and vomiting. The median follow-up was 24.9 months. Two-year overall survival was 91% and 2-year disease-free survival was 83%.Conclusion Hyperthermia combined with chemotherapy to produce radiosensitization for locally advanced fixed primary rectal cancer is followed by a high R0 resection rate, with toxicity comparable with standard regimens.Keywords Fixed rectal cancer, chemoradiotherapy, hyperthermia, metronidazoleWhat does this paper add to the literature?The results of a phase II trial testing a new chemoradiotherapy regime with local hyperthermia for locally advanced fixed T4 rectal cancer treatment are presented. They show considerable improvement in the R0 resection rate for patients considered unresectable or borderline at presentation.

Long-term local control and survival after preoperative radiochemotherapy in combination with deep regional hyperthermia in locally advanced rectal cancer

“…A recent prospective phase II study applied a quadrimodal preoperative regimen for locally advanced fixed (T4) rectal cancers. Treatment consisted of hypofractionated radiotherapy with concomitant capecitabine and oxaliplatin, rectal metronidazole and capacitative hyperthermia with a target temperature of 41-45 C. The authors report a complete resection rate of 92% and a local failure rate of 13.6% after a median follow-up of 24.9 months [19]. These numbers are superior to data reported before for this population with a very high risk for local failure [20].…”

Integrating Hyperthermia into Modern Radiation Oncology: What Evidence Is Necessary?

“…In a further retrospective study encompassing 235 patients, HT appeared to confer better downstaging of the primary tumor and involved lymph nodes (95). Two small studies evaluated hypofractionated RTHTCT schemes showing principal efficacy and safety (96, 97). Additional HT appears to be well tolerated without increased impairment of quality of life (98).…”

Future directions in combined modality therapy for rectal cancer: reevaluating the role of total mesorectal excision after chemoradiotherapy

“…In a retrospective review of 106 patients, Schroeder et al found that patients treated with the addition of regional hyperthermia had improved pCR rates (16.4% versus 6.7%) 40. However, two single-group Phase II studies combining hyperthermia with nCRT found similar pCR compared with nCRT alone 41,42. Therefore, the role of hyperthermia is unclear.…”