Summary
Rebeccamycin analog (NSC 655649) is a synthetic antibiotic cytotoxic agent thought to inhibit topoisomerase function. We sought to determine the response rate to rebeccamycin analog among patients with refractory advanced breast cancer using two different treatment schedules. Eligible patients had measurable disease, central venous access, and one or two prior chemotherapy regimens for advanced cancer, or recurrence within 12 months of adjuvant chemotherapy. Patients were randomized to rebeccamycin analog on one of two treatment schedules: arm 1, 500 mg/m2 IV bolus every 21 days; arm 2, 140 mg/m2 IV bolus daily ×5 days, every 21 days. The primary study endpoint was response rate; a two stage accrual design evaluated each schedule separately. Forty-two women entered the trial, 21 on each arm. Prior chemotherapy regimens for metastatic breast cancer were: 0, n=4; 1, n=21; 2, n=17. Prior treatments (including adjuvant therapy) anthracyclines: 88%, taxanes 67%, 5FU-based therapy, 50%. There were 5 partial responses (overall response rate 12%), two in arm 1 and 3 in arm 2, all in patients with prior anthracycline-based adjuvant chemotherapy. Median time to progression was 2.1 months (range 1–14+ months). An additional 9 patients had stable disease as best response. Grade 3 or 4 toxicity rates were: anemia 5%, neutropenia 33%, thrombocytopenia 12%, RBC transfusion 14%, nausea/vomiting 10%. Toxicity profiles were similar between the treatment arms. Rebeccamycin analog is reasonably well tolerated on two different treatment schedules for advanced breast cancer, with modest clinical activity in this heavily pretreated population.
Similar content being viewed by others
References
Prudhomme M (2003) Rebeccamycin analogues as anti-cancer agents. Eur J Med Chem 38:23–140
Merchant J, Tutsch K, Dresen A, Arzoomanian R, Alberti D, Feierabend C, Binger K, Marnoccha R, Thomas J, Cleary J, Wilding G (2002) Phase I clinical and pharmacokinetic study of NSC 655649, a rebeccamycin analogue, given in both single-dose and multiple-dose formats. Clin Cancer Res 8:2193–2201
Tocher AW, Beckahrdt SG, Kuhn J, Hammong L, Weiss G, Rizzo J, Aylesworth C, Hidalgo M, Putnik A, Schwartz G, Felton S, Campbell E, Rowinsky EK (2001) Phase 1 and pharmacokinetic study of NSC 655649, a rebeccamycin analogue with topoisomerase inhibitor properties. J Clin Oncol 19:2937–2947
Dowlati A, Hoppel CL, Ingalls ST, Majka S, Li X, Dedransk N, Spiro T, Gerson SL, Ivy P, Remick SC (2001) Phase I clinical and pharmacokinetic study of rebeccmycin analog NSC 655649 given daily for five consecutive days. J Clin Oncol 19:2309–2318
Therase P, Arbuck SG, Eisenhauer EA, Wanders J, Kaplan RS, Rubinstein L, Verweij J, Van Glabbeke M, Van Oosterom AT, Christian MC, Gwyther SG (2000) New guidelines to evaluate the response to treatment in solid tumors. J Natl Cancer Inst 92:205–216
Hussain M, Vaishampayan U, Heilbrun LK, Jain V, LoRusso PM, Ivy P, Flaherty L (2003) A phase II study of rebeccamycin analog (NSC-655649) in metastatic renal cell cancer. Invest New Drugs 21:465–471
Goel S, Wadler S, Hoffman A, Volterra F, Baker C, Nazario E, Ivy P, Silverman A, Mani S (2003) A phase II study of rebeccamycin analog NSC 655649 in patients with metastatic colorectal cancer. Invest New Drugs 21:103–107-471
Dowlati A, Chapman R, Subbiah S, Fu P, Ness A, Cortas T, Patrick L, Reynolds S, Xu N, Levitan N, Ivy P, Remick SC (2005) Randomized phase II trial of different schedules of administration of rebeccamycin analogue as second line therapy in non-small cell lung cancer. Invest New Drugs 23:1–5
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
About this article
Cite this article
Burstein, H.J., Overmoyer, B., Gelman, R. et al. Rebeccamycin analog for refractory breast cancer: A randomized phase II trial of dosing schedules. Invest New Drugs 25, 161–164 (2007). https://doi.org/10.1007/s10637-006-9007-6
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s10637-006-9007-6