Herceptin with Weekly Taxol and Platinum as First Line Treatment in HER2 Positive Metastatic Breast Cancer:
Final Results of a phase II study 

Aim of Work: The experimental and clinical data on the potential synergy between Herceptin and some chemotherapeutic agents especially Platinum/Taxanes are extremely encouraging and warrants further studies aiming at exceeding the benefit shown with Herceptin and Taxanes alone.

Patients and Methods: From Jan 2001 to Feb2004, 22 cases with HER2 positive (+3 by IHC) metastatic breast cancer were included in this phase II study. All patients received the following regimen as first line treatment for their disease:

Herceptin                     4mg/kg (loading)           then 2mg/kg/week

Cisplatinum                   25mg/m2                      D1 + D8 + D15

Taxol                            60mg/m2 (3H)              D1 + D8 + D15

Cisplatinum and Taxol were recycled on day 29.

In case of objective response or stable disease, six cycles were given then patients were maintained on Herceptin (6mg/kg/3weeks) until disease progression. The primary end points were response rate and toxicity profile and the secondary end points were response duration, TTP and overall survival.

Results: The median age of the included patients was 47 years (range 31-65years). All patients were evaluated for treatment toxicity and efficacy. All patients except two had prior adjuvant Anthracycline based regimen. Fifteen cases had visceral disease (68%) while eighteen patients (81%) had more than one involved organ. The overall response rate was 77% (CR: 6 cases, PR: 11 cases) with a response duration ranging from 3 months – 36 months (median 13 months). The one and two years survival rate for the whole group was 90% and 60% respectively. The main adverse events were grade II neuropathy in two cases (9%), neutropenic fever (9%), grade III anorexia and vomiting (13%) and fatigue (18%). No clinical cardiac toxicity were encountered, however, three cases (13%) developed more than 10% reduction in their LVEF (by echocardiogram).

Of notice is the high incidence if brain metastasis which was observed in eight cases (36%) at a follow up period of 2-40 months from the initiation of therapy (median 11 months).         

 Conclusion: The combination of Herceptin with weekly Taxol and Platinum is extremely effective and well tolerated. There was an extremely high incidence of brain metastasis in these patients; a point which was also reported by others

Other Breast Cancer Articles:

   - Hercepin: Taming of a bad gene

   - Docetaxel/cisplatinum metastatic breast cancer previously exposed To anthracycline

   - Temodal in the treatment of brain metastasis of mammary origin