title: A phase II clinical and pharmacological study of oral 9-nitrocamptothecin in patients with refractory epithelial ovarian, tubal or peritoneal cancer.
abstract: 9-Nitrocamptothecin (9-NC) is a water-insoluble topoisomerase I inhibitor with a broad antitumor activity in animal models. A phase II study was performed in patients with heavily refractory ovarian, tubal or peritoneal cancer (median number of previous chemotherapy regimens > 3) to determine the activity of a daily oral dose of 9-NC. 9-NC dose was 1.5 mg/m2/day for four consecutive days every week. Increments of 0.25 mg/day were authorized in patients without significant side effects. Of 29 evaluable patients, a 7% remission rate was observed. Thirty-four percent of patients had stable disease. The median survival was 8 months. Toxicity was evaluated in 31 patients. Grade 3 or 4 hematologic toxicity consisted of anemia in 10 patients (32%), neutropenia in eight (26%) and thrombocytopenia in three (10%). Grade > or = 2 non-hematologic toxic effects were nausea and vomiting in 26 (84%), diarrhea in 12 (39%), weight loss in seven (22%), chemical cystitis in six (19%) and neutropenic sepsis in six (19%). 9-NC was tolerated for sustained periods of time in some patients (up to 47 weeks). The observed 8-month survival in such a refractory patient population is noteworthy. Further clinical research of prolonged exposure to less toxic analogs of 9-NC is warranted.
authors.affiliation: The University of Texas MD Anderson Cancer Center, Houston 77030, USA. cverschr@notes.mdacc.tmc.edu
authors.forename: C F
authors.initials: CF
authors.lastname: Verschraegen
authors.forename: E
authors.initials: E
authors.lastname: Gupta
authors.forename: E
authors.initials: E
authors.lastname: Loyer
authors.forename: J J
authors.initials: JJ
authors.lastname: Kavanagh
authors.forename: A P
authors.initials: AP
authors.lastname: Kudelka
authors.forename: R S
authors.initials: RS
authors.lastname: Freedman
authors.forename: C L
authors.initials: CL
authors.lastname: Edwards
authors.forename: N
authors.initials: N
authors.lastname: Harris
authors.forename: M
authors.initials: M
authors.lastname: Steger
authors.forename: V
authors.initials: V
authors.lastname: Steltz
authors.forename: B C
authors.initials: BC
authors.lastname: Giovanella
authors.forename: J S
authors.initials: JS
authors.lastname: Stehlin
mesh_terms: D000284:Administration, Oral; D000328:Adult; D000368:Aged; D000970:Antineoplastic Agents / Q000009:adverse effects / Q000493:pharmacokinetics / Q000627:therapeutic use*; D002166:Camptothecin / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000493:pharmacokinetics / Q000627:therapeutic use; D018572:Disease-Free Survival; D005185:Fallopian Tube Neoplasms / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology; D005260:Female; D006801:Humans; D008875:Middle Aged; D010051:Ovarian Neoplasms / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology; D010534:Peritoneal Neoplasms / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology; D015996:Survival Rate
chemical_list: D000970:Antineoplastic Agents; C079905:rubitecan; D002166:Camptothecin