Leptomeningeal carcinomatosis after major remission to taxane-based front-line therapy in patients with advanced breast cancer

Aim: To determine the incidence of leptomeningeal carcinomatosis (LMC), as the first manifestation of systemic progression, in breast cancer patients after obtaining a major response (complete response, CR or >80% partial response, PR) to first-line taxane-based chemotherapy treated between 1996 and 2000 in our Medical Oncology Unit. Patients and methods: Patients with histologically proven breast cancer having either metastatic disease, or high-risk locoregional disease that were entered into treatment protocols with first-line taxane (paclitaxel or docetaxel) plus anthracyclines or mitoxantrone combinations and developed LMC as the first evidence of progression after major response (CR or >80% PR) were analyzed in the present study (n=155). Results: Seven patients with a median age of 54 (range: 40-70) years developed LMC as their first evidence of progression after taxane-based regimens with a median interval of 6 months (range: 2-18) from start of treatment to diagnosis of LMC. Five patients received intrathecal (i.t.) methotrexate treatment and whole brain radiotherapy (RT), while one patient received i.t. methotrexate and RT to lumbar spine. Two patients responded to treatment for LMC, while two achieved stable disease and three progressed. Two patients had elevated cerebrospinal fluid tumor markers (more than serum marker levels) that proved useful in monitoring response to treatment. Median survival after LMC was 3.6 months (range: 1-31+) and correlated positively to the interval from the initiation of taxane-based therapy to LMC (r=0.84, P=0.019). Seven out of 86 responders (8.1%; 95% confidence interval, 2.4-13.9) developed LMC as the first sign of progression after a major response to first-line chemotherapy. Conclusions: LMC after a major response to front-line taxane-based regimens represents a grave disease manifestation and its incidence appears increased when compared in retrospect to non-taxane-treated patients. Prospective evaluation of the incidence of LMC after taxane versus non-taxane-based treatment from large randomized multi-institutional trials is warranted and identification of potential prognostic factors might help identify patients requiring appropriate prophylactic therapy.