Assessment of Sertoli cell functional reserve and its relationship to sperm parameters.

Sertoli cell functional reserve was assessed in normozoospermic men and oligozoospermic patients and its prognostic potential was evaluated for patient selection and treatment. For the first objective, three groups of normo-follicle-stimulating hormone (FSH)/normozoospermic fertile men (n:12), normo-FSH/oligozoospermic (n:21) and hyper-FSH/oligozoospermic subfertile men participated in the study whereas for the second objective 24 normo-FSH oligozoospermic patients volunteered for a pilot therapeutic trial. For the first part, high purity (hp) FSH (225 i.u., i.m.), human chorionic gonadotropin (hCG) (1500 i.u., i.m.) or their combination was given separately at weekly intervals, with samplings at 0, 3, 24 and 48 h. For the pilot trial, rec-FSH (150 i.u./48 h, i.m.) or placebo were prescribed for 6 months. The main outcome measures for the study were inhibin-B (inh-B), insulin-like growth factor (IGF)-I, testosterone and oestradiol concentrations and the main sperm parameters. Bolus administration of hp-FSH or hp-FSH/hCG combination in normozoospermic men resulted in a significant rise of inh-B in normozoospermic men (mean +/- SD, basal: 183.8+/-24.2 pg/mL in hp-FSH and 175.2+/-23.5 in hp-FSH/hCG treatment; 48 h: 256.1+/-34.2 and 246.3+/-19.0, respectively, p<0.001 for both). In oligozoospermic groups basal inh-B concentration was lower than in normozoospermic men (normo-FSH: 117.4+/-16.5, hyper-FSH: 81.2+/-19.8, p<0.001 for both) with a post-stimulation increase noted only in normo-FSH patients (hp-FSH 24-h: 132.8+/-19.7, p<0.01; hp-FSH/hCG 0 min: 105.7+/-20.1, 24-h: 119.5+/-20.6, p<0.05). Total sperm number and progressive motility showed significant improvements (p<0.05 for both) after 6 months of rec-FSH treatment in the group of patients with a satisfactory response to hp-FSH stimulation. In conclusion, the basal and reserve activity of Sertoli cells, as judged by inh-B secretion, was higher in normozoospermic than in dyspermic men, with a better therapeutic outcome noted in those patients with an adequate response to hp-FSH stimulation.

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 multiinstitutional trials is warranted and identification of potential prognostic factors might help identify patients requiring appropriate prophylactic therapy.

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.