ABDOMINOPELVIC HYPERTHERMIA AND INTRAPERITONEAL CARBOPLATIN IN EPITHELIAL OVARIAN-CANCER - FEASIBILITY, TOLERANCE AND PHARMACOLOGY

Purpose: To investigate the feasibility, toxicity, and pharmacokinetic s of intraperitoneal (i.p.) carboplatin (CB) with concomitant abdomino -pelvic hyperthermia (HT) in advanced ovarian cancer patients. Methods and Materials: Patients with residual disease mainly confined to the peritoneal cavity after platinum based chemotherapy received an initia l course of i.p. CB for baseline pharmacokinetics followed by three cy cles of i.p. CB with concomitant regional hyperthermia. The goal of HT was to achieve at least 45 min of intraperitoneal temperature >42 deg rees but <50 degrees C while maintaining normal tissue temperatures <4 3 degrees C and systemic body temperatures <38 degrees C. No analgesic premedication was used. Thermometry was recorded by multisensor fiber optic probes placed within the peritoneal cavity, bladder, vagina, and oral cavity. Results: Thirteen patients received a total of 31 sessio ns. Our intraperitoneal temperature goal could not be achieved because of patient intolerance. At best, we could maintain intraperitoneal te mperatures >40 degrees C, for more than 40 min in 7 of 31 sessions. Th e average values of thermal variables were T-90 = 40 degrees C, T-AVE = 41 degrees C, T-MIN = 38.2 degrees C, and T-MAX = 42.9 degrees C. Th e mean maximum systemic temperature was 38 degrees C. Acute thermal to xicities requiring early interruption of hyperthermia were systemic te mperature exceeding 38 degrees C (11 of 31), abdominal pain or general ized distress (20 of 31), and vomiting (2 of 31). Hematological toxici ties were not increased by hyperthermia. Pharmacokinetics were consist ent with enhanced clearance of CB by HT. Lower radio frequencies (<75 MHz) achieved better heat deposition in the peritoneal cavity than hig her frequencies (>75 MHz). Two of the 13 patients (a Stage III and a S tage IV patient) are alive with no evidence of disease at 40 and 43 mo nths from treatment. Conclusions: Intraperitoneal temperatures in the range of 40 degrees C maintained for approximately 40 min can be achie ved within the described setting. The probability of successful induct ion of therapeutic intraperitoneal temperatures appears to be higher w hen frequencies below 75 MHz are used. Patients who are potentially pl atinum sensitive and have minimal residual disease could potentially b enefit from the combined treatment under the conditions studied. Howev er, this temperature-time range appears inadequate against platinum re sistant disease, and/or bulky residual pelvic disease. Alternative app roaches such as whole body hyperthermia and carboplatin are warranted to overcome some of the obstacles observed.