A retrospective study evaluating a fixed low dose capecitabine monotherapy in women with HER-2 negative metastatic breast cancer.

To determine if a low fixed dosing strategy of capecitabine would produce comparable clinical activity with less adverse toxicities compared to published data with higher doses in the setting of metastatic breast cancer (mBC). We retrospectively analyzed patients treated with a low fixed dose of capecitabine (CAPE-L) at 1,000 mg twice daily for 14 days every 21 days. Outcomes included clinical benefit rate (CBR), overall response rates (ORR), time to progression (TTP), and overall survival (OS). A historical comparison group of mBC patients treated on 12 prior trials at the package-insert dose of capecitabine (n = 1,949) was utilized. Eighty-six patients were analyzed in our cohort. Positive hormone receptor status (79.1 vs. 50.6 %), and capecitabine as first-line chemotherapy (44.2 vs. 16.5 %) were more frequent in our cohort relative to the historical comparison. The median starting dose in our cohort was 633.5 mg/m(2). The CBR was similar between the CAPE-L and the standard dose cohorts (55.8 vs. 49.5 %), as was ORR (24.3 vs. 24 %), and median TTP (7 mo, 95 % CI 5.5-8.5 vs. 5.1 mo, 95 % CI 4.5-5.7). Median OS was longer in our cohort (24 mo, 95 % CI 16.8-31.2) than the historic standard dose cohort (12.1 mo, 95 % CI 9.6-14.4), a difference that was likely explained by the higher proportion of patients in the CAPE-L cohort who received capecitabine as first-line chemotherapy and who had hormone receptor positive disease. As expected, adverse events were less frequent with CAPE-L. We found that CAPE-L, which translates into a dose of 600-650 mg/m(2), appeared to have good clinical efficacy and acceptable toxicity.

Pattern of use of adjuvant chemotherapy for stage II colon cancer: a single-institution experience.

PURPOSE: American Society of Clinical Oncology (ASCO) guidelines define high-risk prognostic features (HRFs) in stage II colon cancer and recommend limiting adjuvant chemotherapy to patients with HRFs. We evaluated the extent to which HRFs influenced decisions on adjuvant chemotherapy before and after publication of the guidelines. PATIENTS AND METHODS: We reviewed data from 100 consecutive patients with stage II colon cancer resected between January 2000 and June 2007. Practice pattern in the pre-guideline era (2000 through 2004) was compared with the post-guideline era (2005-2007). RESULTS: The median age of the cohort was 65.8 years. A total of 60 patients had > or = 1 HRF. Overall, 38% of the patients with HRFs did not receive chemotherapy; 37.5% without HRFs did. Seventy-one percent of the patients given adjuvant chemotherapy had HRFs versus 48% of the patients not given chemotherapy. There was no association between the presence/absence of HRFs and chemotherapy (P = .25). The association between number of HRFs per individual and chemotherapy was significant (P = .0255). Bowel obstruction and T4 disease were the only individual HRFs significantly associated with chemotherapy (P = .0059 and .0294, respectively). A significant drop in use of chemotherapy for all patients occurred after publication of the guidelines, but this was caused mostly by a drop in treatment for patients with HRFs from 80% to 36% (P = .001). CONCLUSION: Decisions for or against adjuvant chemotherapy did not adhere completely to ASCO guidelines. Publication of the guidelines led to a significant drop in appropriate use of adjuvant chemotherapy in high-risk patients.

Docetaxel and carboplatin as first-line therapy in advanced non-small cell lung carcinoma: a phase II study.

BACKGROUND: Taxanes have been widely used against advanced non-small cell lung cancer (NSCLC), alone and in combination with platinum agents. In order to develop a tolerable palliative regimen, we combined carboplatin with low dose docetaxel. PATIENTS AND METHODS: Chemotherapy-naive patients, with Stage IIIB or IV NSCLC and an ECOG performance status < or = 2, were enrolled. Treatment consisted of docetaxel 60 mg/m2 and carboplatin AUC 6 every 21 days. Therapy continued for 1 year or 6 months beyond best response, whichever was greater. RESULTS: Twenty-five patients were enrolled. Most patients (80%) had Stage IV disease. The partial response rate was 16%. Response duration ranged from 6 to 115 weeks. Median survival was 55 weeks. Toxicity was generally limited to grade 3 or 4 neutropenia. There was 1 septic death. CONCLUSION: Survival compared favorably to other similar trials employing higher doses of docetaxel. Additionally, a hematologic toxicity advantage was seen compared to regimens containing higher doses of docetaxel.

Does race affect outcomes in triple negative breast cancer?

BACKGROUND: There is discordance among studies assessing the impact of race on outcome of patients with Triple Negative Breast Cancer (TNBC). We assessed survival outcomes for African American (AA) versus Caucasian (CA) women with TNBC treated at an urban cancer center in Memphis, TN with a predominant AA patient population. METHODS: Patients with Stage I-III TNBC were identified from our breast database. Event free survival (EFS) and Breast cancer specific survival (BCSS) were the primary outcome measures. Cox proportional hazards models were fitted for EFS and BCSS. RESULTS: Of the 124 patients, 71% were AA. No significant association between race and stage (P = 0.21) or menopausal status (P = 0.15) was observed. Median age at diagnosis was significantly lower for AA versus CA women (49.5 vs. 55 years, P = 0.024). 92% of the patients received standard neo/adjuvant chemotherapy, with no significant difference in duration and type of chemotherapy between the races. With a median follow up of 23 months, 28% of AA vs. 19% of CA women had an event (P = 0.37). 3 year EFS and BCSS trended favorably towards CA race (77% vs. 64%, log rank P = 0.20 and 92% vs. 76%, P = 0.13 respectively) with a similar trend noted on multiple variable modeling (EFS: HR 0.62, P = 0.29; BCSS: HR 0.36, P = 0.18). AA women >/=50 years at diagnosis had a significantly worse BCSS than the CA women in that age group (P = 0.012). CONCLUSION: Older AA women with TNBC have a significantly worse breast cancer specific survival than their CA counterparts. Overall, there is a trend towards lower survival for AA women compared to Caucasians despite uniformity of tumor phenotype and treatment. The high early event rate, irrespective of race, underscores the need for effective therapies for women with TNBC.

Pattern of Use of Adjuvant Chemotherapy for Stage II Colon Cancer: A Single-Institution Experience.

Purpose: American Society of Clinical Oncology (ASCO) guidelines define high-risk prognostic features (HRFs) in stage II colon cancer and recommend limiting adjuvant chemotherapy to patients with HRFs. We evaluated the extent to which HRFs influenced decisions on adjuvant chemotherapy before and after publication of the guidelines. Patients and Methods: We reviewed data from 100 consecutive patients with stage II colon cancer resected between January 2000 and June 2007. Practice pattern in the pre-guideline era (2000 through 2004) was compared with the postguideline era (2005-2007). Results: The median age of the cohort was 65.8 years. A total of 60 patients had >/= 1 HRF. Overall, 38% of the patients with HRFs did not receive chemotherapy; 37.5% without HRFs did. Seventy-one percent of the patients given adjuvant chemotherapy had HRFs versus 48% of the patients not given chemotherapy. There was no association between the presence/absence of HRFs and chemotherapy (P = .25). The association between number of HRFs per individual and chemotherapy was significant (P = .0255). Bowel obstruction and T4 disease were the only individual HRFs significantly associated with chemotherapy (P = .0059 and .0294, respectively). A significant drop in use of chemotherapy for all patients occurred after publication of the guidelines, but this was caused mostly by a drop in treatment for patients with HRFs from 80% to 36% (P = .001). Conclusion: Decisions for or against adjuvant chemotherapy did not adhere completely to ASCO guidelines. Publication of the guidelines led to a significant drop in appropriate use of adjuvant chemotherapy in high-risk patients.

Phase II study of vinorelbine and low-dose docetaxel in chemotherapy-naive patients with hormone-refractory prostate cancer.

PURPOSE: Vinorelbine, a semisynthetic vinca alkaloid, and docetaxel, a semisynthetic taxane, are active single agents in hormone-refractory prostate cancer and have demonstrated synergy in tumor cell lines and animal models. This study was designed to assess the efficacy and tolerability of vinorelbine and low-dose docetaxel in chemotherapy-naive, hormone-refractory prostate cancer patients whose disease had progressed after withdrawal from anti-androgens, despite castrate testosterone levels. PATIENTS AND METHODS: Patients with histologically confirmed hormone-refractory prostate cancer despite testosterone levels < or = 50 ng/mL, Karnofsky performance status > 70, and adequate bone marrow reserve were enrolled. They received vinorelbine, 20 mg/m2, followed by docetaxel, 25 mg/m2, on days 1 and 8 of a 21-day cycle. Tumor response was defined by prespecified reductions from baseline prostate-specific antigen levels or bidimensionally measurable disease. Adjustments in the dose of either agent were based on > or = grade 2 toxicity according to standard criteria. RESULTS: Twenty-one patients with a mean age of 76 years (range, 60-83 years) and a median prostate-specific antigen level of 116 ng/mL (range, 10.4-4,262 ng/mL) were enrolled and received a total of 152 courses (median, 7.5 courses) of vinorelbine and docetaxel. Of the 19 patients who were evaluable for biochemical response, prostate-specific antigen reductions from baseline of > 75%, > or = 50% to < or = 75%, and < 50% were observed in eight, three, and seven patients, respectively (median prostate-specific antigen decrease, 60% +/- 31%). Of five patients with measurable disease, three were evaluable: one patient had a complete response, and two had partial responses at the site of measurable disease. The vinorelbine/docetaxel doublet was generally well tolerated. In the first two cycles of therapy, six patients had grade 3 and eight patients had grade 4 neutropenia as their worst-grade toxicities; all cases were manageable with granulocyte colony stimulating factor support. Acute respiratory distress syndrome was observed in one patient. There were few dose reductions or interruptions. DISCUSSION: Vinorelbine, 20 mg/m2, and low-dose docetaxel, 25 mg/m2, given on days 1 and 8 every 21 days, is a well-tolerated regimen with biochemical and objective response rates comparable to standard therapies in patients with hormone-refractory prostate cancer. A multicenter, randomized trial is under way to compare vinorelbine plus low-dose docetaxel with estramustine plus higher-dose docetaxel (60 mg/m2).

Phase II trial of weekly vinorelbine and trastuzumab as first-line therapy in patients with HER2(+) metastatic breast cancer.

PURPOSE: Human epidermal growth factor receptor 2 (HER2) overexpression is associated with a more aggressive form of breast cancer that responds well to trastuzumab therapy. Trastuzumab-based combination regimens have shown greater antitumor activity than chemotherapy alone. These findings, coupled with the favorable antitumor activity and tolerability profile of vinorelbine in breast cancer, provided the rationale for investigating the novel combination of vinorelbine and trastuzumab. PATIENTS AND METHODS: A phase II, open-label trial of intravenous vinorelbine (30 mg/m(2) on day 1, then weekly) and trastuzumab (4 mg/kg on day 0, then 2 mg/kg weekly) was conducted in previously untreated HER2(+) metastatic breast cancer patients. Vinorelbine dose was adjusted for grade 3/4 neutropenia; patients remained on combination therapy until disease progression or patient withdrawal due to adverse events. RESULTS: Of 40 enrolled patients (median age 51 years, range 30-82), 37 were evaluable for response. Overall response rate was 78% (29/37, 95% confidence interval [CI] 62%-90%), including four (11%, 95% CI 3%-25%) complete and 25 (68%) partial responses. Objective tumor response correlated with degree of HER2 positivity: immunohistochemistry (IHC) 3(+) = 82% (18/22) response and IHC 2(+) = 58% (7/12) response. Median time to progression was 72 weeks (95% CI 37-138 weeks); median survival has not been reached. Grade 3/4 neutropenia was the most frequent serious toxicity and cause of dose reductions (9% of courses) and omissions (10% of courses). No patient experienced serious cardiac toxicity. CONCLUSIONS: Weekly vinorelbine/trastuzumab offers a high therapeutic index as initial therapy in patients with HER2(+) metastatic breast cancer. Further investigation of this novel regimen is planned.