Isolated leptomeningeal carcinomatosis (carcinomatous meningitis) after taxane-induced major remission in patients with advanced breast cancer.
OBJECTIVE
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.


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.
Kosmas
Christos
C
Department of Medicine, Medical Oncology Unit, Helena-Venizelou Hospital, Athens, Greece. ckosm@ath.forthnet.gr
Malamos
Nikolaos A
NA
Tsavaris
Nikolas B
NB
Stamataki
Melina
M
Gregoriou
Achilleas
A
Rokana
Sofia
S
Vartholomeou
Maria
M
Antonopoulos
Minas J
MJ
D000328:Adult; D000368:Aged; D001943:Breast Neoplasms / Q000150:complications* / Q000188:drug therapy; D003131:Combined Modality Therapy; D018450:Disease Progression; D000077143:Docetaxel; D005260:Female; D006801:Humans; D015994:Incidence; D008577:Meningeal Neoplasms / Q000139:chemically induced* / Q000737:chemistry / Q000453:epidemiology / Q000401:mortality / Q000532:radiotherapy; D008581:Meningitis / Q000208:ethnology; D008727:Methotrexate / Q000009:adverse effects / Q000627:therapeutic use*; D008875:Middle Aged; D009367:Neoplasm Staging; D017239:Paclitaxel / Q000009:adverse effects* / Q000031:analogs & derivatives*; D011446:Prospective Studies; D012008:Recurrence; D012074:Remission Induction; D015996:Survival Rate; D043823:Taxoids
D043823:Taxoids; D000077143:Docetaxel; D017239:Paclitaxel; D008727:Methotrexate