Minimal clinical benefit of single agent Orathecin (Rubitecan) in heavily pretreated metastatic breast cancer.
OBJECTIVE
The purpose of this phase II study was to evaluate the efficacy and tolerability of Orathecin, an oral camptothecin analog that has exhibited antitumor activity in breast cancer patients during preclinical studies.


METHODS
Sixteen patients with metastatic breast cancer previously treated with anthracycline and taxane were utilized in the study. Orathecin was administered orally at 1.5 mg/m2 /day for the first five consecutive days of the cycle followed by 2 days of rest on a 7-day schedule. The end points of the study were efficacy and toxicity.


RESULTS
The median age of the patients was 51 years (range, 35-73). Eight patients (50%) had multiple disease sites, and nine patients (56%) received more than three chemotherapy regimens. All patients were evaluated for toxicity, three patients were removed from the study for toxicity or disease progression prior to 8 weeks and were thus not evaluated for efficacy. The median follow-up was 110 days (range, 15-554). There were no responses to treatment. Five of the 13 evaluable patients (38%) had stable disease, eight (61%) had progressive disease. Most adverse events were mild to moderate in intensity. The median time to progression (TTP) for evaluable patients was 109 days (range, 56-374 days) (lower 95% C.I., 57 days). The median survival time was 272 days (lower 95% C.I., 209 days).


CONCLUSIONS
Orathecin at the dose and regimen used in this study resulted in no objective tumor responses for this heavily pretreated population. Accurate risk stratification strategies can improve patients' selection and contribute to determine the appropriate benefit of therapies in MBC.
Chedid
Silwan
S
Department of Breast Medical Oncology, M. D. Anderson Cancer Center, The University of Texas, 1515 Holcombe Boulevard, Unit 424, Houston, TX, 77030-4095, USA.
Rivera
Edgardo
E
Frye
Debbie K
DK
Ibrahim
Nuhad
N
Esteva
Francisco
F
Valero
Vicente
V
Hortobagyi
Gabriel
G
Mettinger
Karl L
KL
Cristofanilli
Massimo
M
D000328:Adult; D000368:Aged; D000972:Antineoplastic Agents, Phytogenic / Q000009:adverse effects / Q000627:therapeutic use*; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000473:pathology; D002166:Camptothecin / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000627:therapeutic use; D018450:Disease Progression; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D008875:Middle Aged; D009362:Neoplasm Metastasis; D011446:Prospective Studies; D016896:Treatment Outcome
D000972:Antineoplastic Agents, Phytogenic; C079905:rubitecan; D002166:Camptothecin