Efficacy of weekly trastuzumab and paclitaxel in the treatment of women with HER-2/neu overexpressing metastatic breast cancer. The impact of taxane free interval on treatment outcomes

Abstract

Purpose. Trastuzumab is known as an active agent in HER2/neu overexpressing metastatic breast cancer. In the prospective study we investigated efficacy, safety and toxicity of trastuzumab and paclitaxel in metastatic breast cancer progressing on previous therapy.

Patients and methods. We accrued 17 patients with histologically confirmed breast cancer, Karnofsky performance status at least 60 %, median age 50 (36-66), pretreated with at least two regimens. HER-2/neu expression was tested by HercepTest (r) (DAKO) in all 17 patients. Fifteen specimens were 3+ positive and 2 specimens 2+ positive. All patients except one were pretreated with taxanes. Taxane free interval (TFI) was defined as a time from last taxane administration until the beginning of the study for every enrolled patient. TFI longer than 1 year was found in 7 patients. TFI shorter than 1 year was observed in 9 patients. Trastuzumab was given 4 mg/kg i.v. as a loading dose followed by 2 mg/kg i.v. weekly. Paclitaxel was given 80 mg/m2 i.v. weekly until disease progression or unacceptable toxicity. We assessed the response rate (RR), the time to progression (TTP), the survival (OS) and toxicity.

Results. In the intent to treat population we found objective response in 10 patients (59 %), including 2 complete responses (CR). In the subset with TFI > 1 year we observed response in 4 cases including 1 CR (RR 57 %). In TFI ≤ 1 year subgroup we observed response in 6 cases also with 1 CR (RR 67 %). TFI was not statistically significant for response (p < 0,4349). Median TTP is 6 month with 4 patients remaining progression free. Patients with TFI > 1 year tend to have longer TTP (p = 0,0201). Median OS has not been reached with 10 patients surviving. We administered 599 cycles including 473 cycles of trastuzumab and paclitaxel with no dose adjustment. One patient developed hypersensitivity reaction on the first trastuzumab infusion and was excluded from study. The most common toxicity was trastuzumab infusion related pyretic reaction observed in 6 patients. Dose limiting adverse effect which led to the treatment discontinuation was cardiotoxicity. Ejection fraction decline grade 2 occurred in 1 patient and grade 3 also in 1 patient. Six patients experienced grade 3 neuropathy. There were observed 1 episode of grade 4 neutropenia and grade 3 anemia. We noted 4 episodes of grade 3 infection without neutropenia. Grade 3 elevation of liver function tests occurred in 6 patients with no need of dose reduction. There were observed 1 episode of grade 3 hyperglycemia and 1 episode of grade 3 weight gain. Other grade 3 or 4 toxicity was not detected.

Conclusions. Trastuzumab and paclitaxel have shown activity and good tolerability in HER-2/neu overexpressing metastatic breast cancer patients. Tumor response in 10 responding taxanes pretreated patients was independent on TFI, but patients with longer TFI tend to be longer progression free.