Isolated Leptomeningeal Carcinomatosis (Carcinomatous Meningitis) after Taxane-Induced Major Remission in Patients with Advanced Breast Cancer

OBJECTIVES: To identify the incidence of leptomeningeal carcinomatosis (LMC), as the first site of systemic progression, in breast cancer patients after having obtained a major response (CR or near CR) to first-line taxane-based chemotherapy and compare these findings in retrospect with a matched-pair group of historical control patients from our database treated with nontaxane regimens. 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), and compared, as regards the incidence of LMC, to a matched-pair retrospective group of 155 patients treated with nontaxane regimens in our unit. RESULTS: Seven patients with a median age of 54 years (range 40-70) 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 1 patient received i.t. methotrexate and RT to the lumbar spine. Two patients responded to treatment for LMC, while 2 achieved stable disease and 3 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 1-17+) 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 (8.13%) in the taxane group versus 1 out of 72 responders (1.4%) in the non-taxane-treated group developed LMC as the first sign of progression after a major response to first-line chemotherapy (p < 0.1). CONCLUSIONS: LMC after a major response to front-line taxane-based regimens represents a grave disease manifestation and its incidence appears increased, but not significantly so, when compared retrospectively 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 to identify patients requiring appropriate prophylactic therapy.