Biweekly paclitaxel plus gemcitabine in advanced breast cancer: phase II trial and predictive value of HER2 extracellular domain.
BACKGROUND
We wanted to assess the toxicity and efficacy of paclitaxel plus gemcitabine in advanced breast cancer and to confirm whether circulating HER2 extracellular domain (ECD) correlates with treatment response.


METHODS
Forty-three patients received paclitaxel 150 mg/m2 followed by gemcitabine 2500 mg/m2, both on day 1 of 14-day cycles, with a maximum of eight cycles. Serum levels of HER2 ECD were assessed by ELISA.


RESULTS
All patients were evaluable for toxicity and 42 for efficacy. Overall toxicity was low. Grade 3 neutropenia occurred in 12% of patients and grade 4 in 17%, and other grade 3 toxicities in <5%. One patient had an allergic infusion reaction. Overall response rate was 71% [95% confidence interval (CI) 62% to 81%], with 11 patients achieving a complete response (26%). With a median follow-up of 26 months, the median time to progression was 16.6 months. Response rate correlated significantly with HER2 ECD, with 42% of HER2 ECD-positive patients responding versus 83% of HER2 ECD-negative patients (P = 0.02). Furthermore, response duration was shorter in patients with positive HER2 ECD levels (7.9 versus 14.4 months; P = 0.04).


CONCLUSIONS
Paclitaxel plus gemcitabine given as an every 2-weeks schedule is a well tolerated and active regimen in advanced breast carcinoma. This is an attractive combination to use when anthracyclines are not indicated, such as in HER2 positive cases that receive trastuzumab. In addition, elevated levels of HER2 ECD adversely affect the efficacy of treatment.
Colomer
R
R
Institut Català d'Oncologia, Hospital Dr Josep Trueta, Girona, Spain. rcolomer@icogirona.scs.es
Llombart-Cussac
A
A
Lluch
A
A
Barnadas
A
A
Ojeda
B
B
Carañana
V
V
Fernández
Y
Y
García-Conde
J
J
Alonso
S
S
Montero
S
S
Hornedo
J
J
Guillem
V
V
D000230:Adenocarcinoma / Q000188:drug therapy* / Q000235:genetics* / Q000473:pathology; D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000235:genetics* / Q000473:pathology; D004273:DNA, Neoplasm / Q000032:analysis; D003841:Deoxycytidine / Q000008:administration & dosage / Q000031:analogs & derivatives*; D018450:Disease Progression; D018572:Disease-Free Survival; D004334:Drug Administration Schedule; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D018734:Genes, erbB-2; D006801:Humans; D007262:Infusions, Intravenous; D008875:Middle Aged; D017239:Paclitaxel / Q000008:administration & dosage; D011237:Predictive Value of Tests; D011379:Prognosis; D016896:Treatment Outcome; D000093542:Gemcitabine
D004273:DNA, Neoplasm; D003841:Deoxycytidine; D017239:Paclitaxel; D000093542:Gemcitabine