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


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 multiinstitutional trials is warranted and identification of potential prognostic factors might help identify patients requiring appropriate prophylactic therapy.
Kosmas
Christos
C
Department of Medicine, Helena-Venizelous Hospital, Athens University School of Medicine, Greece. ckosm@ath.forthnet.gr
Malamos
Nikolaos A
NA
Tsavaris
Nicolas B
NB
Stamataki
Melina
M
Stefanou
Stefanos
S
Gregoriou
Achilleas
A
Rokana
Sofia
S
Vartholomeou
Maria
M
Antonopoulos
Minas J
MJ
D000328:Adult; D000368:Aged; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000009:adverse effects* / Q000627:therapeutic use; D001943:Breast Neoplasms / Q000188:drug therapy*; D001952:Bridged-Ring Compounds / Q000009:adverse effects*; D018450:Disease Progression; D005260:Female; D006801:Humans; D007278:Injections, Spinal; D008577:Meningeal Neoplasms / Q000139:chemically induced / Q000188:drug therapy / Q000453:epidemiology / Q000209:etiology*; D008727:Methotrexate / Q000008:administration & dosage / Q000627:therapeutic use; D008875:Middle Aged; D012189:Retrospective Studies; D013120:Spinal Cord Neoplasms / Q000737:chemistry / Q000188:drug therapy / Q000453:epidemiology / Q000209:etiology*; D043823:Taxoids; D013997:Time Factors; D016896:Treatment Outcome
D000970:Antineoplastic Agents; D001952:Bridged-Ring Compounds; D043823:Taxoids; C080625:taxane; D008727:Methotrexate