ISSN:
1569-8041
Keywords:
cisplatin
;
epithelial ovarian cancer
;
etoposide
;
intraperitoneal chemotherapy
;
survival analysis
Source:
Springer Online Journal Archives 1860-2000
Topics:
Medicine
Notes:
Abstract Background: High-dose platinum-based regimens can produce responses inpatients not responding to standard chemotherapy. As in many ovarian cancerpatients the disease remains confined to the peritoneal cavity,intraperitoneal (i.p.) chemotherapy has been applied as an alternativeapproach to increase drug exposure. The delivery of cytotoxic agents to theperitoneal cavity can lead to high drug concentrations intraperitoneallywith less systemic toxicity. This study aimed at evaluating the efficacy andtoxicity of high-dose i.p. cisplatin plus etoposide and intravenous sodiumthiosulphate protection in ovarian cancer. Patients and methods: Patients with either a pathologically completeresponse (pCR) after first-line treatment or with persistent disease afterfirst-line platinum-based chemotherapy or abdominal recurrences wereeligible. All intraabdominal lesions had to be 〈2 cm at the start of i.p.treatment. The treatment consisted of etoposide 350 mg/m2 i.p.followed by cisplatin 200 mg/m2 i.p. with intravenous sodiumthiosulphate (4 g/m2 bolus, followed by 12 g/m2over six hours) protection. Four courses of i.p. treatment were administeredin case of pCR and 6 courses otherwise, at four-weekly intervals. Results: The study comprised 29 patients, six patients with pCR, 17patients with persistent disease and six patients with abdominalrecurrences. They received a total of 105 courses of treatment (65%of the scheduled number of courses). Twelve patients completed scheduledtreatment, illustrating its feasibility. In 17 patients treatment had to beprematurely stopped because of inflow obstruction (seven patients), bowelperforation (two patients), renal toxicity (two patients), neurotoxicity(two patients), or malaise and vomiting (four patients). One patient withbowel perforation died of this complication. Severe nausea and vomitingoccurred in 51% of cycles. Leukopenia and thrombopenia grade 3 and 4occurred in 30% and 6% of cycles, respectively. Ototoxicity ofcisplatin was measured by serial tone audiography in 23 patients: only eightpatients (35%) showed significant audiographic changes, although noneof them developed clinical hearing loss. Fifteen patients were evaluable forresponse: four pCR, five PR, two SD, four PD. The median duration of freedomfrom progression was 616 days and the median overall survival 1065 days fromthe start of treatment. Conclusions: High-dose i.p. treatment with cisplatin and etoposide can beassociated with significant toxicities. Major clinical problems are nausea,vomiting, and the formation of intraabdominal adhesions. Intravenous sodiumthiosulphate effectively reduces the systemic toxicity of high-dose cisplatin.The value of high-dose i.p. treatment is uncertain and its routine use cannotbe recommended.
Type of Medium:
Electronic Resource
URL:
http://dx.doi.org/10.1023/A:1008296202198
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