Combined doxorubicin and paclitaxel in advanced breast cancer: effective and cardiotoxic.
BACKGROUND
Paclitaxel has shown activity in metastatic breast cancer, including anthracycline-resistant breast cancer. The efficacy, toxicity and optimal scheduling of the combination of the two drugs needs to be defined.


METHODS
Thirty women with advanced breast cancer who had undergone at most one prior adjuvant chemotherapy regimen, were treated at three different dose levels with doxorubicin (50, 60 and 60 mg/m2) followed 30 minutes later by paclitaxel (155, 175 and 200 mg/m2, respectively) every 3 weeks.


RESULTS
The overall response rate was 83% (95% CI: 64-94), with 24% of patients achieving CR. The median response duration for complete responders was 11 months (range 4-14+) and median survival 18 months (range 3-28+). Two hundred sixty-five treatment courses were given (median 9, range 3-13) and the median cumulative dose of doxorubicin was 369 mg/m2 (range 114-550). The main toxicities were neutropenia, parestesia, nausea/vomiting, alopecia, myalgia and cardiotoxicity. Fifteen patients (50%) had reductions of left ventricular ejection fraction of below normal levels and 6 of these patients (20%) developed congestive heart failure.


CONCLUSIONS
The combination of doxorubicin and paclitaxel is highly active, but is accompanied by the dose-limiting toxic effects of neutropenia, neuropathy and cardiotoxicity.
Department of Oncology, Herlev University Hospital, Denmark.
J
J
Gehl
M
M
Boesgaard
T
T
Paaske
B
B
Vittrup Jensen
P
P
Dombernowsky
D000328:Adult; D000368:Aged; D000903:Antibiotics, Antineoplastic / Q000008:administration & dosage; D000972:Antineoplastic Agents, Phytogenic / Q000008:administration & dosage; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage / Q000009:adverse effects* / Q000627:therapeutic use*; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000473:pathology*; D002490:Central Nervous System / Q000187:drug effects*; D018572:Disease-Free Survival; D004305:Dose-Response Relationship, Drug; D004317:Doxorubicin / Q000008:administration & dosage; D005260:Female; D005500:Follow-Up Studies; D006321:Heart / Q000187:drug effects*; D006801:Humans; D007262:Infusions, Intravenous; D008875:Middle Aged; D009362:Neoplasm Metastasis; D017239:Paclitaxel / Q000008:administration & dosage; D015996:Survival Rate
D000903:Antibiotics, Antineoplastic; D000972:Antineoplastic Agents, Phytogenic; D004317:Doxorubicin; D017239:Paclitaxel