A phase I study of cetuximab in combination with paclitaxel in patients with advanced-stage breast cancer Journal Article
| Authors: | Modi, S.; D'Andrea, G.; Norton, L.; Yao, T. J.; Caravelli, J.; Rosen, P. P.; Hudis, C.; Seidman, A. D. |
| Article Title: | A phase I study of cetuximab in combination with paclitaxel in patients with advanced-stage breast cancer |
| Abstract: | Background: The epidermal growth factor receptor (EGFR) is part of the ErbB family of receptor tyrosine kinases and is known to be variably expressed in breast cancers. Cetuximab is a humanized monoclonal antibody directed against the EGFR that works by blocking the downstream signaling function of this protein and thereby interfering with cancer cell proliferation. Preclinical studies have indicated a synergistic effect for the combination of anti-EGFR therapy plus paclitaxel in breast cancer models. Patients and Methods: Hence, we conducted a dose-escalation phase I trial using cetuximab/paclitaxel in patients with metastatic breast cancer to eveluated the feasibility of this combination. Patients with EGFR-positive metastac breast cancer treated with ≤ 1 previous therapy, excluding taxanes, were eligible. Treatment consisted of weekly cetuximab theraphy and every-3-week paclitaxel, with dose escalation of cetuximab until the maximum tolerated dose was reached. Results: Twelve patients were enrolled to 3 treatment cahorts. Two of 6 patients of on the second cohort (cetuximab 100 mg/m 2) developed dose-limiting toxicities, presenting as grade 3 rash. The third cohort was amended to allow the same cetuximab dose but to modify the paclitaxel to a weekly schedule. Despite this, 1 of 3 patients in this group also developed grade 3 skin toxicity as a dose-limiting toxicity; thus, the trial was stopped. Ten of the 12 patients were evaluable for response, and of these, 2 patients experienced stable disease, and 8 patients experienced disease progression. Conclusion: Because of prohibitive dermatologic toxicity and disappointing preliminary efficacy, the combination of paclitaxel/ cetuximab was not considered promising in this population, although further study of this regimen might be warranted. |
| Keywords: | adult; clinical article; human tissue; treatment outcome; aged; middle aged; antibiotic agent; clinical trial; constipation; drug tolerability; fatigue; neutropenia; advanced cancer; area under the curve; cancer growth; diarrhea; dose response; drug dose reduction; drug efficacy; drug safety; drug withdrawal; skin toxicity; paclitaxel; cancer patient; cancer staging; drug megadose; neurotoxicity; drug eruption; infection; liver toxicity; pain; breast cancer; anemia; bone marrow suppression; leukopenia; mucosa inflammation; nausea; stomatitis; vomiting; antineoplastic combined chemotherapy protocols; myalgia; epidermal growth factor receptor; cohort analysis; steroid; receptor, epidermal growth factor; breast neoplasms; cetuximab; arthralgia; drug hypersensitivity; fever; rash; drug synergism; maculopapular rash; antibodies, monoclonal; feasibility study; neoplasm metastasis; granulocyte colony stimulating factor receptor; open study; receptor, erbb-2; bacteremia; headache; metastasis potential; drug blood level; maximum tolerated dose; phase 1 clinical trial; taxane derivative; sensory dysfunction; drug half life; cancer control; corticosteroid; motor dysfunction; toxicity; anthracycline; drug dose regimen; drug treatment failure; metastatic breast cancer; alopecia; infusions, intravenous; epistaxis; clinical trials; cellulitis; histamine h2 receptor antagonist; gastritis; skin edema; folliculitis; dose escalation; histamine h1 receptor antagonist |
| Journal Title: | Clinical Breast Cancer |
| Volume: | 7 |
| Issue: | 3 |
| ISSN: | 1526-8209 |
| Publisher: | Elsevier Inc. |
| Date Published: | 2006-08-01 |
| Start Page: | 270 |
| End Page: | 277 |
| Language: | English |
| PUBMED: | 16942645 |
| PROVIDER: | scopus |
| DOI: | 10.3816/CBC.2006.n.040 |
| DOI/URL: | |
| Notes: | --- - "Cited By (since 1996): 43" - "Export Date: 4 June 2012" - "CODEN: CBCLB" - "Source: Scopus" |
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