Overview and new strategies in metastatic breast cancer (MBC) for treatment of tamoxifen-resistant patients.

The treatment with aromatase inhibitors (AIs) and fulvestrant has been demonstrated to be active in a proportion of tamoxifen-resistant breast cancer patients, obtaining, in some cases, a long-term control of tumor growth. Results from clinical trials indicate that treatment with fulvestrant might either precede or follow AIs. However, the AIs are now replacing tamoxifen as first-line advanced and adjuvant therapies, and thus, other options following tamoxifen failure are required. Fulvestrant may be effective in this setting, even if there is also evidence of a lack of cross-resistance between nonsteroidal and steroidal AIs, resulting in the potential use of steroidal AIs following nonsteroidal AI failure and vice versa. Resistance mechanisms to these therapies appear to be related to a cross talk between estrogen receptor (ER) and growth factor-signaling cascades. Novel therapeutic approaches for ER+ patients, which combine hormonal agents and signal transduction inhibitors, have been developed to overcoming resistance. Several trials are now investigating signal transduction inhibitors combined with endocrine agents. This approach might provide efficient treatments and delay the onset of antihormone resistance, thereby significantly improving patient's survival.

Phase II study of gemcitabine and cisplatin in patients with advanced or metastatic bladder cancer: long-term follow-up of a 3-week regimen.

BACKGROUND: Bladder cancer is the fifth most common cancer among men and the seventh among women. At diagnosis, at least 25% of bladder cancer tumors are locally or systemically advanced. Systemic chemotherapy is the only current modality for advanced or metastatic transitional cell carcinoma of the bladder. Recently, a phase III randomized study has demonstrated that the regimen with gemcitabine (GMC) and cisplatin (CDDP) had a survival advantage similar to the standard M-VAC (methotrexate, vinblastine, doxorubicin and cisplatin), with a better safety profile. AIM: It was the aim of this study to evaluate the tumor response rate, the median time to progression, the median survival and toxicity in a 21-day schedule with GMC and CDDP in patients with advanced/metastatic bladder cancer. PATIENTS AND METHODS: From September 1998 to December 2000, 27 patients with advanced/metastatic transitional cell carcinoma were enrolled. All patients received 1,200 mg/m(2) GMC administered as a 30-min intravenous infusion on days 1 and 8, and 75 mg/m(2) CDDP as a 1-hour infusion on day 2. Cycles were repeated every 21 days. The patients had a median age of 59.8 years (range 39-75) and an Eastern Cooperative Oncology Group performance status of 0-2. RESULTS: Twenty-five patients were valuable for toxic effects, length of survival and tumor response. The statistical analysis was performed in May 2004. Mean and median follow-up were 20.23 and 13.2 months (range 2-68), respectively. The overall remission rate (complete response + partial response) was 48% (95% CI 28.4-67.6%). The median time to progression was 9 months (range 2-56). The median duration of survival for all patients was 13.2 months (range 2-68+), with 1-year and 23-month survival rates of 60 and 20%, respectively. There was no grade 4 toxicity or treatment-related death. Grade 3 anemia was observed in 4 patients (16%) and grade 3 thrombocytopenia occurred in 6 patients (24%). No grade 3-4 nausea/vomiting or neutropenia was observed. CONCLUSION: GMC and CDDP is an active schedule with a good safety profile in a 21-day regimen. It may be a valid alternative to the standard 28-day regimen due to its high tumor response and survival with a low incidence of toxicity, especially in pretreated and metastatic patients.

Resistance to PGE2 inhibition of PWM-stimulated lymphocytes from neoplastic patients.

PGE2 treatment of mononuclear cells from patients with different types of neoplasias was unable to decrease either the number of plaque-forming cells or the expression of CD71 and CD25 in PWM-driven cultures. In contrast, in previous studies, PGE2 inhibited these parameters in cultured mononuclear cells from normal volunteers. Surgical treatment of cancer patients did not modify the lymphocyte sensitivity to PGE2 after 1 week, but at 2 and 6 months after therapeutical treatment, the inhibition values of the parameters studied were almost similar or very similar to those of normal lymphocytes. The reduction of PGE2 sensitivity in cancer patients was related to the increase of PGE2 levels and, probably, to a PGE2 receptor saturation. A restoration of PGE2-induced inhibition some months after therapy could be due to the decrease in PGE2 levels and to receptor unsaturation.