Trastuzumab and gemcitabine as salvage therapy in heavily pre-treated patients with metastatic breast cancer

Cancer Chemother Pharmacol. 2008 Oct;62(5):903-10. doi: 10.1007/s00280-008-0682-1. Epub 2008 Feb 7.

Abstract

Purpose: In Her2-postive metastatic breast carcinoma, first-line trastuzumab-based therapy is well established; many centres continue antibody treatment beyond disease progression. In this trial, we evaluated the efficacy and safety of gemcitabine and trastuzumab after earlier exposure to anthracyclines, docetaxel and/or vinorelbine, and trastuzumab.

Methods: Twenty-nine consecutive patients were included as eligible. Patients received gemcitabine at a dose of 1,250 mg/m2 on day one and eight, every 21 days. Trastuzumab was administered in three-week cycles. Clinical benefit rate (CBR; CR + PR + SD > or = 6 months) was defined as primary endpoint.

Results: As of July 2007, all patients are evaluable for toxicity, and 26 for response. Earlier therapies consisted of trastuzumab (100%), anthracyclines (100%), vinorelbine (96.6%), docetaxel (72.4%), and capecitabine (72.4%). 19.2% of patients experienced PR, and SD > or = 6 months was observed in a further 26.9%, resulting in a CBR of 46.2%. Time to progression was median 3 months, and overall survival 17 months. Neutropenia (20.7%), thrombocytopenia (13.8%), and nausea (3.4%) were the only treatment-related adverse events that occurred with grade 3 or 4 intensity. Four patients (13.8%) developed brain metastases while on therapy.

Conclusions: While CBR was low when compared to trastuzumab-based first-line therapy, it is higher than what would be expected from gemcitabine monotherapy in a similar setting. Together with the favourable toxicity profile, this regimen appears to be a safe and potentially effective salvage therapy option in a heavily pre-treated population.

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Antibodies, Monoclonal / administration & dosage
  • Antibodies, Monoclonal, Humanized
  • Antimetabolites, Antineoplastic / administration & dosage
  • Antineoplastic Agents / administration & dosage
  • Antineoplastic Combined Chemotherapy Protocols / adverse effects
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use*
  • Breast Neoplasms / drug therapy*
  • Breast Neoplasms / pathology
  • Deoxycytidine / administration & dosage
  • Deoxycytidine / analogs & derivatives
  • Disease Progression
  • Female
  • Gemcitabine
  • Humans
  • Middle Aged
  • Neoplasm Metastasis
  • Salvage Therapy*
  • Trastuzumab
  • Treatment Failure

Substances

  • Antibodies, Monoclonal
  • Antibodies, Monoclonal, Humanized
  • Antimetabolites, Antineoplastic
  • Antineoplastic Agents
  • Deoxycytidine
  • Trastuzumab
  • Gemcitabine