International Phase Iii Trial Of Chemo Radiotherapy +/- Hyperthermia For Locally Advanced Cervix Cancer: Interim Update On Toxicities

Several randomized studies demonstrate a benefit to adding cisplatin (CDDP) based chemotherapy to radiotherapy (RT) for cervix cancer. The Dutch phase III pelvic tumor trial demonstrates a survival and local control benefit to the addition of hyperthermia (HT) to RT. We summarize an ongoing international phase III trial centered on the role of HT in locally advanced cervix cancer, and update an interim analysis on treatment related toxicities. Locally advanced cervix cancer patients without paraaortic nodal involvement are screened for eligibility on the basis of FIGO stage, tumor histology, renal function, performance status, and suitability for hyperthermia treatment. Eligible patients, after informed consent, are randomized to chemoradiation versus chemoradiation with weekly hyperthermia. Radiation and chemotherapy are standardized external beam radiation to the whole pelvis, with concurrent weekly cisplatin 40 mg/m2. Low dose rate or high dose rate brachytherapy boosts are delivered, with sidewall boosts as appropriate. Deep whole pelvis hyperthermia is delivered with a BSD 2000 using the sigma ellipse applicator, one weekly treatment on the day of cisplatin infusion. Thermometry catheters are placed in the rectum and foley catheter for normal tissue monitoring. Catheters are also placed in the cervix for monitoring tumor related thermal dose delivered. To date, 84 patients have enrolled on this trial. The overall grade 3 and 4 toxicity appears balanced between the two arms, and the hyperthermia toxicity to date has all been grade 1. Patient demographics and early toxicity data will be reviewed in detail. As mandated by the NCI data safety and monitoring board, no formal comparisons of failure free survival and overall survival are made at this time. In phase II series published to date, trimodality therapy for locally advanced cervical cancer resulted in an excellent clinical response and was well tolerated. The interim results of this phase III trial offer further confirmation that hyperthermia is well tolerated. The addition of HT to chemoradiotherapy represents a promising new strategy which deserves continued multi-institutional and international collaborative efforts.