Phase II trial of weekly nanoparticle albumin-bound paclitaxel with carboplatin and trastuzumab as first-line therapy for women with HER2-overexpressing metastatic breast cancer Journal Article
| Authors: | Conlin, A.; Seidman, A.; Bach, A.; Lake, D.; Dickler, M.; D'Andrea, G.; Traina, T.; Danso, M.; Brufsky, A.; Saleh, M.; Clawson, A.; Hudis, C. |
| Article Title: | Phase II trial of weekly nanoparticle albumin-bound paclitaxel with carboplatin and trastuzumab as first-line therapy for women with HER2-overexpressing metastatic breast cancer |
| Abstract: | Purpose: This multicenter phase II trial evaluated the efficacy and safety of weekly nanoparticle albumin-bound paclitaxel with carboplatin and weekly trastuzumab as first-line therapy for women with HER2-overexpressing metastatic breast cancer (MBC). Patients and Methods: We treated 32 patients who had measurable MBC that was HER2-positive defined by an immunohistochemical staining score of 3+ or gene amplification by fluorescence in situ hybridization, required for those with an IHC of 2+. Patients were treated with albumin-bound paclitaxel 100 mg/m2 and carboplatin at area under the curve (AUC) = 2 on days 1, 8, and 15 of a 28-day cycle. Trastuzumab was administered at 2 mg/kg weekly after a loading dose of 4 mg/kg. Because of hypersensitivity reactions occurring during carboplatin infusion numbers 6-8 in 4 of the first 13 patients with this premedication-free regimen, the protocol was amended for carboplatin and dosed at AUC = 6 day 1 each 28-day cycle, in lieu of introducing steroid prophylaxis. Patients were treated with 6 cycles and allowed to continue with all 3 drugs or trastuzumab alone if free of progression and unacceptable toxicity after 6 cycles. Results: The overall response rate (ORR) was 62.5% (95% CI, 45.7%-79.3%) with 3 confirmed complete responders (CRs; 9%) and 17 confirmed partial responses (PRs; 53%). An additional 6 patients (19%) had stable disease (SD) for greater than 16 weeks for a clinical benefit rate (ORR + SD > 16 weeks) of 81%. As of April 16, 2009, 20 patients (63%) had progressed with a median progression-free survival (PFS) of 16.6 months (95% CI, 7.5-26.5 months). Antitumor activity was similar for patients treated with weekly carboplatin and every-4-week carboplatin (ORR, 65% vs. 67%, respectively). Hematologic toxicities were the only grade 4 toxicities noted and were infrequent with grade 4 neutropenia in 3 patients (9%) and 1 febrile neutropenia. Grade 2/3 peripheral neuropathy was uncommon (13%/3%). Conclusion: Weekly albumin-bound paclitaxel with carboplatin and trastuzumab is highly active in HER2-overexpressing MBC. In the absence of corticosteroid premedication, which we avoided with albumin-bound paclitaxel, carboplatin seems best dosed every 4 weeks rather than weekly because of carboplatin-associated hypersensitivity reactions. The regimen was very well tolerated with few grade 3 and 4 nonhematologic toxicities experienced, and severe hematologic toxicity and peripheral neuropathy were infrequent. |
| Keywords: | immunohistochemistry; adult; cancer survival; clinical article; treatment response; aged; disease-free survival; middle aged; clinical trial; fatigue; neutropenia; diarrhea; drug dose reduction; side effect; paclitaxel; in situ hybridization, fluorescence; carboplatin; progression free survival; multiple cycle treatment; phase 2 clinical trial; sensory neuropathy; breast cancer; gene amplification; anemia; leukopenia; nausea; stomatitis; thrombocytopenia; antineoplastic combined chemotherapy protocols; peripheral neuropathy; epidermal growth factor receptor 2; dexamethasone; antineoplastic activity; breast neoplasms; arthralgia; drug dose escalation; febrile neutropenia; rash; drug delivery systems; antibodies, monoclonal; albumin; albumins; fluorescence in situ hybridization; multicenter study; neoplasm metastasis; nanoparticles; receptor, erbb-2; trastuzumab; breast metastasis; desquamation; diphenhydramine; progression-free survival; kaplan-meier estimate; nab-paclitaxel; platinum agents; heart supraventricular arrhythmia; systolic dysfunction |
| Journal Title: | Clinical Breast Cancer |
| Volume: | 10 |
| Issue: | 4 |
| ISSN: | 1526-8209 |
| Publisher: | Elsevier Inc. |
| Date Published: | 2010-08-01 |
| Start Page: | 281 |
| End Page: | 287 |
| Language: | English |
| DOI: | 10.3816/CBC.2010.n.036 |
| PUBMED: | 20705560 |
| PROVIDER: | scopus |
| PMCID: | PMC3883128 |
| DOI/URL: | |
| Notes: | --- - "Cited By (since 1996): 1" - "Export Date: 20 April 2011" - "CODEN: CBCLB" - "Source: Scopus" |
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