AIMS: This Phase II study was conducted to determine the efficacy and toxicity of 9-nitro-camptothecin (9-NC) in patients with previously treated metastatic breast cancer. Pharmacokinetic samples were obtained to investigate the correlation of plasma 9-NC exposure with clinical response and toxicity. PATIENTS AND METHODS: Eligible patients had histologically confirmed metastatic breast cancer with measurable or evaluable disease. Patients must have received one or two prior chemotherapy regimens for metastatic disease. 9-NC was given orally, 1.5 mg/m(2)/day for 5 days each week; response was assessed every 8 weeks. Pharmacokinetic samples were obtained on day 1 of weeks 1 and 5. RESULTS: Eighteen patients were enrolled between September 1999 and May 2000; seventeen patients were evaluable for response. The most common toxicities were nausea, vomiting, urinary symptoms, fatigue and diarrhea. No objective responses were observed; six patients had stable disease. 9-NC apparent clearance ranged from 0.57 to 55.08 L/h (median 5.91 L/h); 9-NC area under the curve ranged from 38 to 2130 ng/ml x h (median 377 ng/ml x h). There was no relationship between pharmacokinetic parameters and individual patient toxicity. CONCLUSION: 9-NC has limited activity in patients with previously treated metastatic breast cancer. Though 9-NC has substantial pharmacokinetic variability in this patient population; no correlation was found between pharmacokinetic variables and toxicity.
AIMS: This Phase II study was conducted to determine the efficacy and toxicity of 9-nitro-camptothecin (9-NC) in patients with previously treated metastatic breast cancer. Pharmacokinetic samples were obtained to investigate the correlation of plasma 9-NC exposure with clinical response and toxicity. PATIENTS AND METHODS: Eligible patients had histologically confirmed metastatic breast cancer with measurable or evaluable disease. Patients must have received one or two prior chemotherapy regimens for metastatic disease. 9-NC was given orally, 1.5 mg/m(2)/day for 5 days each week; response was assessed every 8 weeks. Pharmacokinetic samples were obtained on day 1 of weeks 1 and 5. RESULTS: Eighteen patients were enrolled between September 1999 and May 2000; seventeen patients were evaluable for response. The most common toxicities were nausea, vomiting, urinary symptoms, fatigue and diarrhea. No objective responses were observed; six patients had stable disease. 9-NC apparent clearance ranged from 0.57 to 55.08 L/h (median 5.91 L/h); 9-NC area under the curve ranged from 38 to 2130 ng/ml x h (median 377 ng/ml x h). There was no relationship between pharmacokinetic parameters and individual patienttoxicity. CONCLUSION: 9-NC has limited activity in patients with previously treated metastatic breast cancer. Though 9-NC has substantial pharmacokinetic variability in this patient population; no correlation was found between pharmacokinetic variables and toxicity.
Authors: J L Blum; S E Jones; A U Buzdar; P M LoRusso; I Kuter; C Vogel; B Osterwalder; H U Burger; C S Brown; T Griffin Journal: J Clin Oncol Date: 1999-02 Impact factor: 44.544
Authors: C F Verschraegen; E A Natelson; B C Giovanella; J J Kavanagh; A P Kudelka; R S Freedman; C L Edwards; K Ende; J S Stehlin Journal: Anticancer Drugs Date: 1998-01 Impact factor: 2.248
Authors: E A Natelson; B C Giovanella; C F Verschraegen; K M Fehir; P D De Ipolyi; N Harris; J S Stehlin Journal: Ann N Y Acad Sci Date: 1996-12-13 Impact factor: 5.691
Authors: H L McLeod; F Douglas; M Oates; R P Symonds; D Prakash; A G van der Zee; S B Kaye; R Brown; W N Keith Journal: Int J Cancer Date: 1994-12-01 Impact factor: 7.396