Sequential adjuvant docetaxel and anthracycline chemotherapy for node positive breast cancers: a retrospective study.

PURPOSE: Anthracyclines and taxanes are the most active agents in the adjuvant treatment of breast cancer (BC). They can be used simultaneously or sequentially. The optimal schedule and duration for their administration is unknown. We analyzed the efficacy of sequential adjuvant anthracycline and docetaxel administration in node positive BC patients. METHODS: Node positive BC patients (N=539) from 6 medical oncology centers in Turkey who received sequential adjuvant anthracycline-based regimens and taxane chemotherapy were included in this study between 2006 - 2010. One-hundred and thirty-eight (25%) patients received 3 cycles of anthracycline-based chemotherapy followed by 3 cycles of docetaxel (3+3) and 401 (75%) patients received 4 cycles of anthracycline-based chemotherapy followed by 4 cycles of docetaxel (4+4). Prognostic factors analyzed were estrogen receptor (ER), progesterone receptor (PR), HER2, tumor grade, and nodal status in relation to disease free survival (DFS) and HER2 status in relation to overall survival (OS). RESULTS: The patient median age was 48 years (range 18-79). Most common grade 3-4 toxicities were neutropenia, mucositis and arthralgia. No treatment-related toxic deaths were seen. With a median follow up of 26 months (range 1-115) 61 (11.3%) recurrences and 11 (2%) deaths were registered. Three-year DFS was 81% and OS 96% for all patients. There was no statistically significant difference between 3+3 and 4+4 groups in terms of survival (3-year DFS 88% and 79% [p=0.28] and OS 97% and 95% [p=0.60), respectively). CONCLUSION: Sequential chemotherapy with 4+4 cycles of anthracycline and docetaxel every 3 weeks is an acceptable regimen for adjuvant treatment of node positive BC patients. Duration of chemotherapy should be planned depending on prognostic factors. In this study there was no difference between 3+3 and 4+4 groups in DFS and OS despite the presence of good prognostic factors in the 3+3 group.

D-dimer is a marker of response to chemotherapy in patients with metastatic colorectal cancer.

PURPOSE: D-dimer, LDH and tumor markers are usually overexpressed in colorectal carcinomas (CRC). Our purpose was to assess the prognostic role of D-dimer, lactate dehydrogenase (LDH), CEA, CA19-9 and CA72-4 in patients with metastatic CRC treated with XELOX chemotherapy. METHODS: Thirty-eight CRC patients who had evidence of distant metastasis were enrolled in the study and blood samples were taken before chemotherapy for estimation of the tumor markers CEA, CA19-9 and CA72-4, and for D-dimer and LDH. Patients were randomized into 3 groups: those with partial response (PR), stable disease (SD), and progressive disease (PD) according to their clinical and radiologic evaluation after 3 cycles of XELOX chemotherapy. All parameters were reevaluated after the 3rd cycle of chemotherapy. RESULTS: Eighteen patients (47.3%) achieved PR, 10 (26.3%) SD, and 10 (26.3%) showed PD. After 3 cycles of XELOX CEA (20.55 vs 11.97 ng7sol;ml; p=0.002), LDH (357.50 vs 214.0 U7sol; lt; p=0.001) and D-dimer (1.56 vs 1.17 µgFEU/ml; p=0.022) levels were significantly decreased in the PR group. D-dimer levels were also notably decreased (1.36 vs 0.77 µgFEU/ml; p=0.021) in the SD group. In the PD group a considerable increase was seen in CA 19-9 (119.5 vs 243.09 U/ml; p=0.025), CA 72-4 (5.18 vs 25.8 U/ml; p=0.036) and D-dimer levels (1.77 vs 1.88 µgFEU/ml; p=0.012). CONCLUSION: This study demonstrated that D-dimer, LDH and tumor markers can be helpful in determining CRC prognosis in patients with metastatic disease. D-dimer, LDH and tumor markers provided unique prognostic information in advanced CRC patients.

Prognostic factors in patients with advanced pancreatic cancer treated with gemcitabine alone or gemcitabine plus cisplatin: retrospective analysis of a multicenter study.

PURPOSE: The majority of patients with pancreatic cancer present with advanced disease. Systemic chemotherapy for patients with pancreatic cancer has limited impact on overall survival (OS). Patients eligible for chemotherapy should be selected carefully. The aim of this study was to analyse prognostic factors for OS in advanced pancreatic cancer patients treated with first-line palliative chemotherapy with gemcitabine alone or gemcitabine plus cisplatin. METHODS: We retrospectively reviewed 343 locally advanced or metastatic pancreatic cancer patients who were treated with gemcitabine or gemcitabine plus cisplatin as first-line chemotherapy between December 2000 and June 2011. Fifteen potential prognostic variables were chosen for analysis. Univariate and multivariate analyses were conducted to identify prognostic factors associated with OS. Univariate and multivariate statistical methods were used to determine prognostic factors. RESULTS: Among the 15 variables of univariate analysis, 6 were identified to have prognostic significance: stage (p<0.001), cholestasis (p=0.02), weight loss, prior pancreatectomy, serum CEA level (p<0.001) and serum CA19-9 level (p>0.001). In addition, age, chemotherapy and liver metastasis were of borderline significance (p=0.06). Multivariate analysis (Cox proportional hazard model) included the 6 significant prognostic factors of univariate analysis and showed that stage was independent prognostic factor for OS, as were weight loss, and serum CEA level. CONCLUSION: Stage, weight loss, and serum CEA level were identified as important prognostic factors for OS in advanced pancreatic cancer patients. These findings may also facilitate pretreatment prediction of OS and can be used for selecting patients for treatment.

Gemcitabine and cisplatin combination chemotherapy in triple negative metastatic breast cancer previously treated with a taxane/anthracycline chemotherapy; multicenter experience.

This study was aimed to establish clinical efficacy and tolerability of gemcitabine and cisplatin combination in patients with metastatic triple negative breast cancer progressing after anthracycline and taxane based chemotherapies.Thirty-three patients who were given cisplatin and gemcitabine for triple negative and metastatic breast cancer were evaluated retrospectively. A total of 141 cycles were administered with a median 4 cycles per patient. Median follow-up time was 14 months (range, 2-36 months). Objective response rate was 27.3%. Total clinical benefit of the combination was 48.4%. The estimated median progression free survival and median overall survival were 5 months and 14 months, respectively. The most common Grade 3 and 4 toxicity were neutropenia and thrombocytopenia observed in 10 (27.7%) and 9 (24.9%) patients, respectively. The combination of the gemcitabine and cisplatin after taxane/anthracycline is well tolerated and seems to be effective with acceptable toxicity profile.

Dipyridamole in the treatment of angina pectoris: a meta-analysis.

A meta-analysis was performed to reevaluate the efficacy of dipyridamole for prophylaxis of angina pectoris. We found 10 articles that reported 11 randomized control trials published between 1960 and 1970. Three trials found a statistically significant benefit for the drug vs placebo, four showed a positive trend, two found no difference, and two showed a slight trend favoring placebo. When the results of all 11 trials were combined, two different statistical methods showed a statistically significant benefit from the drug. These combined results must be interpreted cautiously because of excluded patients and other methodologic variations in the studies, as well as evidence from other studies that dipyridamole may aggravate angina. Nevertheless, we conclude that there is some evidence for efficacy of the drug and believe the question should be restudied in larger and better-designed trials.

Meta-analyses of randomized controlled trials.

A new type of research, termed meta-analysis, attempts to analyze and combine the results of previous reports. We found 86 meta-analyses of reports of randomized controlled trials in the English-language literature. We evaluated the quality of these meta-analyses, using a scoring method that considered 23 items in six major areas--study design, combinability, control of bias, statistical analysis, sensitivity analysis, and application of results. Only 24 meta-analyses (28 percent) addressed all six areas, 31 (36 percent) addressed five, 25 (29 percent) addressed four, 5 (6 percent) addressed three, and 1 (1 percent) addressed two. Of the 23 individual items, between 1 and 14 were addressed satisfactorily (mean +/- SD, 7.7 +/- 2.7). We conclude that an urgent need exists for improved methods in literature searching, quality evaluation of trials, and synthesizing of the results.

An analysis of the costs of ambulatory and inpatient care.

Savings resulting from the substitution of ambulatory for inpatient care have been widely reported. This study examined the hypothesis that these savings may result from a reduction of services provided to the ambulatory patient and/or from an incomplete evaluation of these services, when the market value of relatives' support services is not included. Cataract extraction was chosen as an example. Sixty-two medical records of patients admitted to Mount Sinai for cataract extraction in the first six months of 1980 were reviewed, and the cost of their stay was estimated. This cost was then compared to five simulations of home care costs. The simulations differed among themselves primarily as to the experience and training of the person providing nursing services--from an RN to an untrained relative. The quantity and type of service provided to inpatients were assumed to be provided to ambulatory patients in all five simulations. The results of the comparison of hospital costs to home costs were that, in the case of post-cataract extraction, home care is less costly than hospital care either if fewer services are provided to home patients or if the cost of some services assumed by relatives is not calculated.