Phase II trial of high-dose cisplatin with sodium thiosulfate nephroprotection in patients with advanced carcinoma of the uterine cervix previously untreated with chemotherapy Journal Article


Authors: Reichman, B.; Markman, M.; Hakes, T.; Budnick, A.; Rubin, S.; Jones, W.; Almadrones, L.; Lewis, J. L. Jr; Hoskins, W.
Article Title: Phase II trial of high-dose cisplatin with sodium thiosulfate nephroprotection in patients with advanced carcinoma of the uterine cervix previously untreated with chemotherapy
Abstract: Cisplatin is one of the most active single agents in the treatment of advanced cancer of the cervix. The concurrent administration of the nephroprotective agent, sodium thiosulfate, has enabled exploitation of the therapeutic potential of cisplatin. To explore the role of cisplatin dose intensity in the treatment of patients with cancer of the uterine cervix, patients with persistent/recurrent measurable disease were treated with cisplatin at 200 mg/m 2 as a 2-hr infusion with sodium thiosulfate given at 3.3 g/m 2 1 hr prior to cisplatin and 6.6 g/m 2 during the cisplatin infusion. Treatment was repeated monthly. Due to the known cumulative toxcity of cisplatin, treatment beyond two cycles (400 mg/m 2 ) was given only to those patients who had at least demonstrated a PR. Audiologic evaluation was done prior to each cycle of treatment. Eleven patients were entered with a median age of 43 years (range, 25-57), a median KPS of 80% (range, 60-90%), and nine epidermoid and two adenocarcinoma, and all patients had received previous pelvic irradiation. Twenty-eight cycles of treatment were given: 1, five cycles; 3, three cycles; 7, two cycles. No ≥ 3+ hematologic, neurologic, or renal toxicity was demonstrated. Ototoxicity was demonstrated in the mild to moderate hearing loss range (3000-8000 Hz). The greatest threshold shift occurred after the first course of cisplatin. There were three PRs with a maximum duration of 4 months. Due to the significant toxicities encountered, the low response rate, and the limited duration of responses, this trial was closed early to accrual. © 1991.
Keywords: adult; cancer chemotherapy; clinical article; cisplatin; advanced cancer; dose response; treatment planning; drug megadose; neurotoxicity; phase 2 clinical trial; lorazepam; creatinine; dexamethasone; creatinine blood level; urea nitrogen blood level; dose-response relationship, drug; kidney function; carcinoma; thrombocyte count; leukocyte count; metoclopramide; digestive system function disorder; nitrogen; intravenous drug administration; uterine cervix carcinoma; ototoxicity; middle age; urea; drug evaluation; cervix neoplasms; kidney diseases; hearing disorders; sodium thiosulfate; prognosis; human; female; priority journal; article; support, non-u.s. gov't; thiosulfates
Journal Title: Gynecologic Oncology
Volume: 43
Issue: 2
ISSN: 0090-8258
Publisher: Elsevier Inc.  
Date Published: 1991-11-01
Start Page: 159
End Page: 163
Language: English
DOI: 10.1016/0090-8258(91)90064-c
PUBMED: 1743559
PROVIDER: scopus
DOI/URL:
Notes: Article -- Export Date: 27 September 2019 -- Source: Scopus
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MSK Authors
  1. Seth Michael Rubin
    4 Rubin
  2. William Hoskins
    255 Hoskins
  3. Amy S Budnick
    19 Budnick
  4. Lois Ann Cassidy
    72 Cassidy
  5. Thomas B Hakes
    115 Hakes
  6. Walter   Jones
    95 Jones
  7. John   Lewis
    132 Lewis
  8. Maurie Markman
    124 Markman
  9. Stephen C. Rubin
    112 Rubin