Role of gonadotropin-releasing hormone analogues in metastatic male breast cancer: results from a pooled analysis.

BACKGROUND: Male breast cancer is a rare malignancy. Despite the lack of prospectively generated data from trials in either the adjuvant or metastatic setting, patients are commonly treated with hormone therapies. Much controversy exists over the use of gonadotropin-releasing hormone analogues in metastatic male breast cancer patients. We conducted this study to provide more concrete ground on the use of gonadotropin-releasing hormone analogues in this setting. METHODS: We herein present results from a pooled analysis including 60 metastatic male breast cancer patients treated with either an aromatase inhibitor or cyproterone acetate as a monotherapy (23 patients) or combined with a gonadotropin-releasing hormone analogue (37 patients). RESULTS: Overall response rate was 43.5% in patients treated with monotherapy and 51.3% with combination therapy (p = 0.6). Survival outcomes favored combination therapy in terms of median progression-free survival (11.6 months versus 6 months; p = 0.05), 1-year progression-free survival rate (43.2% versus 21.7%; p = 0.05), median overall survival (29.7 months versus 22 months; p = 0.05), and 2-year survival rate (64.9% versus 43.5%; p = 0.05). CONCLUSIONS: In metastatic male breast cancer patients, the combined use of gonadotropin-releasing hormone analogues and aromatase inhibitors or antiandrogens seems to be associated with greater efficacy, particularly in terms of survival outcomes, compared with monotherapy. Collectively, these results encourage considering these agents in the metastatic setting.

Efficacy of chemotherapy in metastatic male breast cancer patients: a retrospective study.

BACKGROUND: The role of chemotherapy in the treatment of metastatic male breast cancer patients remains unknown, and the only available evidence stem from small, retrospective series evaluating outdated drugs and/or regimens. METHODS: In this retrospective study we evaluated the activity of polychemotherapy, consisting of three-drug (anthracycline-containing and anthracycline-free) regimens, as a first-line therapy for metastatic male breast cancer patients who had received at least one prior endocrine therapy. RESULTS: Fifty patients treated between 1978 and 2013 were included in the present analysis. Regarding best response, we recorded 1 (2%) complete response and 27 (54%) partial responses, for an overall response rate of 56% (95% CI, 42.2-69.8). Considering stable disease, the disease control rate was 84%. Median progression-free survival was 7.2 months (95% CI, 5.9-8.5), and median overall survival was 14.2 months (95% CI, 12.2-16.2). Albeit we observed some differences for all the outcomes explored when comparing anthracycline-containing and anthracycline-free regimens, they were not statistically significant. CONCLUSIONS: Chemotherapy, consisting in both anthracycline-containing and anthracycline-free regimens, showed encouraging antitumor activity in metastatic male breast cancer patients previously treated with endocrine therapy.

Docetaxel, oxaliplatin, and capecitabine combination chemotherapy for metastatic gastric cancer.

BACKGROUND: The incorporation of docetaxel into the cisplatin and fluorouracil backbone has been demonstrated to be an active combination in metastatic gastric cancer. Nevertheless, this regimen is burdened by nonnegligible toxicity. We hypothesized that replacing cisplatin and fluorouracil with oxaliplatin and capecitabine should be an active and safe option for metastatic gastric cancer patients. METHODS: In this phase II study, we tested the activity of docetaxel in combination with oxaliplatin and capecitabine (DOC) as a first-line treatment. DOC was administered as follows: docetaxel (60 mg/m(2)) and oxaliplatin (100 mg/m(2)) on day 1, and capecitabine (500 mg/m(2)) was administered orally twice daily given continuously, with cycles repeated every 3 weeks. The primary endpoint was the overall response rate. RESULTS: Forty-eight patients entered the study. All patients had metastatic disease (stage IV). None of the patients had previously received chemotherapy for advanced disease. Performance status was 0, 1, and 2 in 25, 58, and 17 % of patients, respectively; 13 patients (27 %) had adenocarcinoma of the gastroesophageal junction, and 29 patients (60.5 %) had two or more metastatic sites. The overall response rate was 52.1 %. Progression-free survival and overall survival were 6.9 and 12.6 months, respectively. The treatment was well tolerated with no treatment-related deaths. The most common grade 3-4 toxicity was neutropenia (41 %). CONCLUSIONS: DOC is an effective and tolerated first-line treatment, and the lower dose of docetaxel and oxaliplatin used in this study compared with other similar regimens does not seem to hamper the antitumor activity.

FOLFIRI as a second-line therapy in patients with docetaxel-pretreated gastric cancer: a historical cohort.

BACKGROUND: The role of second-line therapy in gastric cancer patients mostly stemmed from clinical trials with monochemotherapy carried out in Asian countries. Nevertheless, these results cannot be broadly generalized as molecular studies suggested the existence of different sets of deregulated gene networks correlated with ethnicity. In the present study, we investigated the activity and safety of FOLFIRI given as a second-line therapy in metastatic gastric or gastro-esophageal junction cancer patients who experienced disease progression on or after first-line docetaxel-containing chemotherapy. METHODS: Patients with histologically confirmed metastatic gastric cancer who failed docetaxel-containing first-line therapy and who received FOLFIRI in second line were eligible for the study. Seventy patients treated at three Italian cancer centers between 2005 and 2012 entered the study. Patients received every 2 weeks irinotecan 180 mg/m2 as 1 h infusion on day 1, folinic acid 100 mg/m2 intravenously days 1-2, and fluorouracil as a 400 mg/m2 bolus and then 600 mg/m2 continuous infusion over 22 hours days 1-2. RESULTS: We observed 1(1.4%) complete response, 15 (21.4%) partial response, for an overall response rate of 22.8% (95% confidence interval (CI): 13.4-32.3). Stable disease was recorded in 21 (30%) patients. Median progression-free survival and overall survival were 3.8 months (95% CI: 3.3-4.4) and 6.2 months (95% CI: 5.3-7.1), respectively. The treatment was well tolerated, as the most common G3-4 toxicities were neutropenia (28.5%) and diarrhea (14.5%). CONCLUSIONS: FOLFIRI appears an effective and safe treatment option for pretreated metastatic gastric cancer patients, and deserves further investigation in randomized clinical trials.

Sequential docetaxel followed by epirubicin-vinorelbine as first-line chemotherapy in advanced breast cancer.

BACKGROUND: This phase II study evaluated the efficacy and the tolerability of a sequential regimen of docetaxel followed by epirubicin-vinorelbine combination as first-line chemotherapy in advanced breast cancer. PATIENTS AND METHODS: Twenty-seven patients received docetaxel 100 mg/m2 (4 cycles) followed by 4 cycles of epirubicin 90 mg/m2 (day 1) combined with vinorelbine 25 mg/m2 (days 1 and 5), with cycles repeated every 3 weeks. G-CSF was administered during epirubicin-vinorelbine treatment. RESULTS: There were 1 (3.7%) CR and 14 (51.9%) PR, for an overall response rate of 55.6% (95% CI, 36.9%-74.3%). Median time to response, time to progression and overall survival were 2, 9 and 25 months, respectively. The dose-limiting toxicity was neutropenia (grade 3 to 4 in 85% of the patients). There was one toxic death due to neutropenic fever. Gastrointestinal side-effects were generally mild According to the Simon two-stage design the response rate was considered unsatisfactory and patient accrual was terminated. CONCLUSION: This sequential regimen appears to be moderately effective; possibly, a modulation of the treatment based on objective responses instead of a fixed number of cycles may be more appropriate in order to obtain better results.

First-line treatment with epirubicin and vinorelbine in metastatic breast cancer.

PURPOSE: This phase II multicenter trial was aimed at investigating the activity of epirubicin-vinorelbine combination as first-line chemotherapy in metastatic breast cancer patients. PATIENTS AND METHODS: Ninety-seven patients with metastatic breast cancer and no prior exposure to anthracyclines received the following regimen: epirubicin 100 mg/m(2) by intravenous (IV) bolus infusion on day 1 plus vinorelbine 25 mg/m(2) by 30-minute IV infusion on days 1 and 5, every 3 weeks for up to eight cycles. All patients also received granulocyte colony-stimulating factor (G- CSF) on days 7 to 12 of every cycle. RESULTS: Objective responses, confirmed at least 4 weeks after the first documentation, were observed in 65 out of 92 assessable patients (70.6%; 95% CI, 62% to 80%). Disease remained stable in 17 patients (18.5%). Responses were observed in all disease sites, being 94% in soft tissue, 60% in bone, and 66% in visceral disease. Median time to response, median duration of response, median time to progression, and median overall survival were 2, 9, 10, and 26 months, respectively. The dose-limiting toxicity was neutropenia, which was grade 4 in 36% of the patients, and was accompanied by fever in 26% of the cases. Grade 3 to 4 mucositis was encountered in 28% of the patients. Other toxicities were mild to moderate. No cardiotoxicity was observed. CONCLUSION: The epirubicin-vinorelbine combination with G-CSF support has been shown in this study to be highly active as first-line treatment of metastatic breast cancer patients, with significant although transient toxicity. This justifies further evaluation in the neoadjuvant setting and in early-stage breast cancer.

Prognostic value of (99m)Tc-sestamibi washout in predicting response of locally advanced breast cancer to neoadjuvant chemotherapy.

UNLABELLED: This study evaluated the role of (99m)Tc-sestamibi washout in the prediction of pathologic tumor response to neoadjuvant chemotherapy in 30 patients with locally advanced breast cancer. METHODS: Two (99m)Tc-sestamibi studies were performed before and after chemotherapy for each patient. Early (10 min) and delayed (240 min) planar breast views were acquired after a 740-MBq (99m)Tc-sestamibi intravenous injection, and the washout rate (WOR) was computed. All patients underwent radical mastectomy with pathologic evaluation of the residual tumor size. RESULTS: The pretherapy (99m)Tc-sestamibi WOR ranged from 14% to 92% (mean +/- SD, 50% +/- 18%). At pathologic examination, 15 patients showed no tumor response to chemotherapy and 15 patients showed an objective response to chemotherapy. The pretherapy (99m)Tc-sestamibi study predicted chemoresistance (WOR > 45%) in 18 of 30 patients and no chemoresistance (WOR < or = 45%) in 12 of 30 patients. When the WOR cutoff was set at >45%, the prognostic performance of the test was indicated by a sensitivity of 100%; a specificity of 80%; positive and negative predictive values of 83% and 100%, respectively; and a likelihood ratio of 5. The repeatability of the test was good, with 80%-93% interreader agreement (kappa = 0.57-0.85). Posttherapy (99m)Tc-sestamibi studies confirmed the pretherapy study prediction in 29 of 30 patients. CONCLUSION: (99m)Tc-Sestamibi WOR is a reliable test for predicting tumor response to neoadjuvant chemotherapy. In fact, negative findings (WOR < or = 45%) rule out chemoresistance and positive findings (WOR > 45%) indicate a high risk of chemoresistance.