Sc. Formenti et al., ABDOMINOPELVIC HYPERTHERMIA AND INTRAPERITONEAL CARBOPLATIN IN EPITHELIAL OVARIAN-CANCER - FEASIBILITY, TOLERANCE AND PHARMACOLOGY, International journal of radiation oncology, biology, physics, 35(5), 1996, pp. 993-1001
Citations number
34
Categorie Soggetti
Oncology,"Radiology,Nuclear Medicine & Medical Imaging
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.