Impact of the extent and duration of cytoreductive surgery on postoperative hematological toxicity after intraperitoneal chemohyperthermia for peritoneal carcinomatosis.
BACKGROUND
Peritoneal carcinomatosis (PC) is a major disease, currently treated using complete cytoreductive surgery and intraperitoneal chemohyperthermia (IPCH). Morbidity is a significant limitation of this procedure, usually related to the extent of surgery, and hematological toxicity, which is considered as dependent upon the chemotherapy dosage alone. The aim of our study was to investigate whether surgery alone had an impact on the hematological toxicity associated with the standardized drug protocol that we routinely prescribed.


METHODS
Data were prospectively recorded from 83 consecutive patients who underwent complete cytoreductive surgery followed by IPCH with intraperitoneal oxaliplatin (360 mg/m(2)) and irinotecan (360 mg/m(2)), in 2 L/m(2) of dextrose over 30 min at 42-45 degrees C, using the Coliseum technique. Sixty minutes prior to IPCH, patients also received an intravenous perfusion of leucovorin (20 mg/m(2)) and 5-fluorouravyl (400 mg/m(2)). The doses and volume of IPCH were determined on the basis of the body surface area, so that all patients received the same concentration of drugs. Severe aplasia were defined as a leucocyte count of <500/ml, platelets <50,000/ml, and reticulocytes <6.5 g Hb/L.


RESULTS
Postoperatively, severe aplasia was seen in 40 of the 83 patients (48%). There was no difference in the characteristics of patients with and without aplasia, other than the extent of surgery. The incidence of severe aplasia was only related to the duration of surgery (537 min in the aplastic group versus 444 min in the non aplastic group) (P = 0.002), and to the extent of the peritoneal disease (peritoneal index of 19.5 in the aplastic group, vs. 15.3 in the nonaplastic group) (P = 0.02).


CONCLUSIONS
We report for the first time that the duration of surgery may increase the incidence of hematological toxicity following intraperitoneal chemotherapy. We also hypothesized that intra- and postoperative transient biochemical disorders, such as hypoalbuminemia, hemodilution, liver, and renal insufficiency and stress can be involved in this process. These hypotheses may allow improved postoperative care.
Elias
Dominique
D
Department of Surgical Oncology, the Institut Gustave Roussy, Tertiary Cancer Center, France. elias@igr.fr <elias@igr.fr>
Raynard
Bruno
B
Boige
Valérie
V
Laplanche
Agnes
A
Estphan
George
G
Malka
David
D
Pocard
Marc
M
D000328:Adult; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D002166:Camptothecin / Q000008:administration & dosage / Q000031:analogs & derivatives*; D003131:Combined Modality Therapy; D004305:Dose-Response Relationship, Drug; D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage; D005947:Glucose / Q000008:administration & dosage; D006438:Hemodilution; D006801:Humans; D006979:Hyperthermia, Induced; D034141:Hypoalbuminemia / Q000209:etiology; D007263:Infusions, Parenteral; D000077146:Irinotecan; D002955:Leucovorin / Q000008:administration & dosage; D008297:Male; D008875:Middle Aged; D009944:Organoplatinum Compounds / Q000008:administration & dosage; D000077150:Oxaliplatin; D010534:Peritoneal Neoplasms / Q000188:drug therapy* / Q000601:surgery*; D011184:Postoperative Period; D011446:Prospective Studies; D012010:Red-Cell Aplasia, Pure / Q000209:etiology*; D016896:Treatment Outcome
D009944:Organoplatinum Compounds; D000077150:Oxaliplatin; D000077146:Irinotecan; D005947:Glucose; D002955:Leucovorin; D005472:Fluorouracil; D002166:Camptothecin