Phase I/II trial of non-cytotoxic suramin in combination with weekly paclitaxel in metastatic breast cancer treated with prior taxanes.
OBJECTIVE
Suramin, a polysulfonated naphthylurea, inhibits the actions of polypeptide growth factors including acidic and basic fibroblast growth factors (aFGF and bFGF), which confer broad spectrum chemotherapy resistance. We hypothesized that suramin at non-cytotoxic doses in combination with weekly paclitaxel would be well tolerated and demonstrate anti-tumor activity.


METHODS
Women with metastatic breast cancer who had been previously treated with a taxane in the adjuvant or metastatic setting were eligible. The primary objective of the phase I was to determine the dose of intravenous (IV) weekly suramin that resulted in plasma concentrations between 10 and 50 umol/l over 8-48 h (or the target range) in combination with IV 80 mg/m(2) of weekly paclitaxel. The primary objective of the phase II trial was to determine the anti-tumor activity of the dosing regimen defined in phase I. Therapy was continued until disease progression or development of unacceptable toxicity.


RESULTS
Thirty-one patients were enrolled (9: phase I; 22: phase II). In phase I, no dose-limiting toxicities were observed. Pharmacokinetics during the first cycle showed suramin concentrations within the target range for 21 of 24 weekly treatments (88 %). In phase II, the objective response rate (ORR) was 23 % (95 % CI 8-45 %), the median progression-free survival was 3.4 months (95 % CI 2.1-4.9 months), and the median overall survival was 11.2 months (95 % CI 6.6-16.0 months).


CONCLUSIONS
Non-cytotoxic doses of suramin in combination with weekly paclitaxel were well tolerated. The efficacy was below the pre-specified criteria required to justify further investigation.
Division of Medical Oncology, Department of Internal Medicine, The Ohio State University Comprehensive Cancer Center, B421 Starling-Loving Hall, 320 West 10th Avenue, Columbus, OH 43210-1240, USA. maryam.lustberg@osumc.edu
Maryam B
MB
Lustberg
Shubham
S
Pant
Amy S
AS
Ruppert
Tong
T
Shen
Yong
Y
Wei
Ling
L
Chen
Lisa
L
Brenner
Donna
D
Shiels
Rhonda R
RR
Jensen
Michael
M
Berger
Ewa
E
Mrozek
Bhuvaneswari
B
Ramaswamy
Michael
M
Grever
Jessie L
JL
Au
M Guillaume
MG
Wientjes
Charles L
CL
Shapiro
D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D001943:Breast Neoplasms / Q000097:blood / Q000188:drug therapy* / Q000473:pathology; D018572:Disease-Free Survival; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D005221:Fatigue / Q000139:chemically induced; D005260:Female; D016222:Fibroblast Growth Factor 2 / Q000097:blood; D006801:Humans; D007970:Leukopenia / Q000139:chemically induced; D008875:Middle Aged; D009325:Nausea / Q000139:chemically induced; D009362:Neoplasm Metastasis; D017239:Paclitaxel / Q000008:administration & dosage / Q000009:adverse effects; D013498:Suramin / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics; D043823:Taxoids / Q000008:administration & dosage; D016896:Treatment Outcome
D043823:Taxoids; D016222:Fibroblast Growth Factor 2; D013498:Suramin; D017239:Paclitaxel