The comparison of FOLFOX regimens with different doses of 5-FU for the adjuvant treatment of colorectal cancer: a multicenter study.

PURPOSE: We aim to compare the efficiency and toxicity of three different 5-fluorouracil (5-FU) administration types in 5-FU, leucovorin, and oxaliplatin (FOLFOX) combination treatment for adjuvant therapy in colorectal cancer (CRC). METHODS: Five hundred and seventy patients with stage III colorectal carcinoma who received different FOLFOX regimens after curative resection were included. Patients were divided into three groups as FOLFOX-4, modified FOLFOX-6 (mFOLFOX-6), and mFOLFOX-4 for comparison of toxicity and disease-free survival (DFS) and overall survival (OS) times. RESULTS: Three-year DFS rates for FOLFOX-4, mFOLFOX-6, and mFOLFOX-4 groups were 65%, 72%, and 72%, respectively. Five-year OS rates for FOLFOX-4, mFOLFOX-6, and mFOLFOX-4 groups were 69%, 75%, and 67%, respectively. There was no statistically significant difference between the three treatment groups in terms of DFS and OS (p = 0.079, and p = 0.147, respectively). Among grade 1-2 adverse events (AE), thrombocytopenia, neuropathy, and stomatitis were more common in the mFOLFOX-6-treated group. The frequency of grade 1-2 nausea and vomiting were similar in mFOLFOX-6 (36.3% and 24%, respectively) and mFOLFOX-4 (32.4% and 24.7%, respectively) groups but were higher than that in the FOLFOX-4 (19.5% and 11.3%, respectively) group. Among the most common grade 3-4 AE, neutropenia (53.4%, 9%, and 13.5%, respectively) and diarrhea (10.5%, 2.2%, and 2.4, respectively) were more common in FOLFOX-4. The rate of anemia and febrile neutropenia was similar in treatment groups (p = 0.063, and p = 0.210, respectively). CONCLUSION: In the adjuvant treatment of stage III CRC patients, three different 5-FU administration types in FOLFOX combination treatment can be used with similar efficiency and manageable toxicity.

Clinical outcomes in patients who received lapatinib plus capecitabine combination therapy for HER2-positive breast cancer with brain metastasis and a comparison of survival with those who received trastuzumab-based therapy: a study by the Anatolian Society of Medical Oncology.

PURPOSE: In this study, we investigated the effect of lapatinib plus capecitabine treatment in HER2-positive breast cancer patients with brain metastasis. METHODS: Of 405 metastatic breast cancer patients with brain metastases at referral centers in Turkey, 46 were treated with lapatinib plus capecitabine only after the development of brain metastasis. Patients who only received trastuzumab-based therapy after the development of brain metastases were accepted as the historic control group for survival analyses (n = 65). Patients who received both drugs consecutively or sequentially were excluded from the analyses (n = 34). RESULTS: Median age among 46 patients who received lapatinib plus capecitabine therapy was 45 years (27-76), and median time for development of brain metastases was 11.9 months (0-69 months). Twenty-six out of 38 patients who received lapatinib plus capecitabine and had extracranial metastasis showed partial response or stable diseases (68.4 %). Grade 3-4 toxicity was observed in eight patients (17.3 %). Median overall survival (OS) in patients treated with lapatinib plus capecitabine was significantly increased compared to that in patients treated with trastuzumab-based therapy (19.1 vs. 12 months, respectively, p = 0.039). The incidence of cerebral death was slightly decreased in patients who received lapatinib plus capecitabine compared to those who received trastuzumab-based therapy (32 vs. 43.4 %, p = 0.332). In the multivariate analysis, lapatinib plus capecitabine therapy remained an independent positive predictor for survival [odds ratio (OR), 0.57; p = 0.02]. DISCUSSION: Although this retrospective multicenter study had several limitations, the results suggest that undergoing lapatinib plus capecitabine therapy after the diagnosis of brain metastasis may further improve survival compared to undergoing only trastuzumab-based therapy.

Results of adjuvant FOLFOX regimens in stage III colorectal cancer patients: retrospective analysis of 667 patients.

OBJECTIVE: The aim of this study was to assess the use of 5-fluorouracil (5-FU), leucovorin and oxaliplatin (FOLFOX) regimens in clinical practice according to their efficacy and toxicity. METHODS: Patients who received oxaliplatin-containing regimens after curative resection for colorectal carcinoma from 10 different oncology centers between May 2004 and December 2009 were included in the study. All patients were treated with FOLFOX regimens. Patients with rectal carcinoma were also treated with chemoradiotherapy with 5-FU after 2 cycles of a FOLFOX regimen. RESULTS: The median age of the patients was 56 years (range 17-78). Of the total 667 patients, 326 were given FOLFOX-4, 232 were given modified FOLFOX-4 and 109 were given FOLFOX-6. The distribution according to disease stage was 33 patients with stage IIIA colorectal cancer, 382 patients with stage IIIB and 252 patients with stage IIIC. The most common adverse events were neutropenia (54%), nausea (36.9%), neuropathy (38.2%) and anemia (33.1%) for all grades. The median follow-up time was 23 months (range 1-79). Three-year disease-free survival and overall survival were 65 and 85.7%, respectively. CONCLUSION: The different oxaliplatin-containing 5-FU-based adjuvant chemotherapy regimens in patients with stage III colorectal cancer seemed to be at least equal in terms of efficacy regardless of the method of 5-FU administration or oxaliplatin dose.

Clinicopathological features in bilateral breast cancer.

INTRODUCTION AND PURPOSE: The frequency of bilateral breast cancer is 1.4-11.0% among all breast cancers. It can present as synchronous (SC) or metachronous (MC). Data regarding clinical course of bilateral breast cancer are scarce. In this study, we therefore evaluated demographic, pathological and clinical characteristics, treatments and responses in bilateral breast cancer cases; making distinctions between metachronous-synchronous and comparing with historic one-sided data for the same parameters. MATERIALS AND METHODS: One hundred fifty bilateral breast cancer cases from ten different centers between 2000 and 2011 were retrospectively scanned. Age of the cases, family history, menopausal status, pathological features, pathological stages, neoadjuvant, surgery, adjuvant and palliative chemotherapy/radiotherapy were examined in the context of the first and second occurrence and discussed with reference to the literature. RESULTS: Metachronous and synchronous groups showed similar age, menopausal status, tumor type, HER2/neu expression; the family history tumor grade, tumor stage, ER-negativity rate, local and distant metastases rates, surgery, adjuvant chemotherapy application rates were identified as significantly different. Palliative chemotherapy response rate was greater in the metachronous group but median PFS rates did not differ between the groups. CONCLUSION: Although bilateral breast cancer is not frequent, MC breast cancer is different from SC breast cancer by having more advanced grade, stage, less ER expression, more frequent rates of local relapse and distant metastasis and better response to chemotherapy in case of relapse/metastasis.

Biological subtypes and survival outcomes in breast cancer patients with brain metastases (study of the Anatolian Society of Medical Oncology).

BACKGROUND: The aim of this study is to determine the relationship between the survival outcomes and biological subtype in breast cancer patients with brain metastases. METHODS: We retrospectively evaluated clinical data from 422 breast cancer patients with brain metastases between 2001 and 2011 from referral centers in Turkey. The study population was divided into four biological subtypes according to their hormone receptor status and HER2 expression. RESULTS: Systemic treatment prolonged median overall survival (OS) after brain metastases in the entire group (14 vs. 3.2 months, p < 0.001). It also prolonged median OS after brain metastases in the triple negative (7.5 vs. 1.6 months, p = 0.010) and luminal A (14.3 vs. 7.1 months, p = 0.003) subgroups. The median OS for untreated patients, chemotherapy and/or hormonal therapy receiving patients, and chemotherapy and/or hormonal therapy plus targeted therapy receivers was 2, 5.8, and 17.7 months, respectively (p < 0.001), in the HER2-overexpressing subgroup. In the luminal B subgroup, it was 3.7, 5.3, and 15.4 months, respectively (p = 0.003). CONCLUSIONS: The use of systemic therapy improves OS after brain metastases in all biological subgroups. Targeted therapies also improve OS after brain metastases in HER2-positive patients. The combined use of targeted therapies and lapatinib are superior to single use and trastuzumab, respectively, in these patients.

Bevacizumab every 4 weeks is as effective as every 2 weeks in combination with biweekly FOLFIRI in metastatic colorectal cancer.

PURPOSE: The efficacy and tolerability of bevacizumab every 2 or 4 weeks using the same dosage in combination with biweekly FOLFIRI were retrospectively evaluated in metastatic colorectal cancer (mCRC) patients in the first-line and second-line therapy. PATIENTS AND METHODS: A total of 332 patients from six centers were evaluated. The patients had received biweekly FOLFIRI in combination with bevacizumab 5 mg/kg every 2 weeks or every 4 weeks schedule for various reasons in individual patients. RESULTS: Approximately 70 % of all patients had 2-week treatment schedule. In the first-line therapy (n = 240), the overall response rate (ORR) was 34.1 % in 2-week and 36.3 % in 4-week groups. Median progression-free survival (PFS) was 8 months (95 %CI, 6.8-9.2) and 9 months (95 %CI, 6.6-11.4) (p = 0.074), and median overall survival (OS) was 22 months (95 %CI, 15.8-28.2) and 20 months (95 %CI, 8.1-31.9) (p = 0.612) in 2- and 4-week groups, respectively. One-year survival rate was 76.2 % for 2-week group and 73.2 % for 4-week group. In the second-line therapy (n = 92), the ORR was similar between the groups (24.5 vs 25.9 % in 2- and 4-week groups, respectively). Median PFS was 6 months (95 %CI, 4.7-7.3) and 11 months (95 %CI, 6.3-15.7) (p = 0.074), and median OS was 15 months (95 %CI, 9.6-20.4) and 17 months (95 %CI, 13.7-20.3) (p = 0.456) for 2-week and for 4-week groups, respectively. One-year survival rate was 61.3 % for 2-week and 71.3 % for 4-week groups. Toxicity profile was similar in 2- and 4-week groups and included neutropenia, febrile neutropenia, nausea and vomiting, diarrhea, mucositis, bleeding, hypertension, thromboembolism and fistulization. CONCLUSION: Bevacizumab 5 mg/kg every 2 weeks or every 4 weeks in combination with biweekly FOLFIRI had similar efficacy and tolerability in mCRC. Because of the retrospective nature of our study, the data should be examined cautiously. However, our study clearly points out the need for determination of optimum biological dosing interval of bevacizumab in well-designed, prospective, randomized trials.

Primary gastric Hodgkin lymphoma and metachronous early gastric carcinoma: a case report.

Primary Gastric Hodgkin lymphoma is seen very rarely. Primary gastric Hodgkin lymphoma and gastric carcinoma in same patient is very very rare entity. Almost all of the primary gastric lymphoma cases are non-Hodgkin lymphoma type. We report the case of 45-year-old man with 3-month history of abdominal pain and weight loss. Upper gastrointestinal endoscopic examination revealed an ulcerated polypoid mass on greater curve of stomach and histopathological examination of biopsy showed adenocarcinoma. After near total gastrectomy, gastric Hodgkin lymphoma diagnosis was made, and postoperative 4 courses of doxorubicin, bleomycin, vinblastine, dacarbazine (ABVD) regimen were administered, and then total 3,600 cGy radiotherapy was delivered. After 7 years, during control examination, early gastric carcinoma was diagnosed. Our case is very rare entity of gastric Hodgkin lymphoma and metachronous gastric carcinoma. This case also shows the importance of follow-up of patients not only for the relapse of primary disease but also for the development of secondary malignancy which can be diagnosed at early curable stage.

Primary adult soft tissue sarcomas: analysis of 294 patients.

We retrospectively analyzed 294 patients with primary soft tissue sarcoma followed between 1996 and 2002 in Ankara Oncology Hospital. There were 170 male and 124 female patients with the age range of 16-80 years. The primary tumor was in the extremity in 72.9% of the patients. We determined lung metastasis in 102 (85%) out of the 120 patients as distant metastasis. The most common adult sarcomas were liposarcoma (16.3%), malignant mesenchymal tumor (MMT) (13.9%), malignant fibrous histiocytoma (MFH) (11.2%), rhabdomyosarcoma (10.2%) and synovial sarcoma (10.2%). Seventeen patients (5.3%) had grade 1 tumor, 143 patients (52.2%) had grade 2 tumor, and 112 patients (41.4%) had grade 3 tumor. In 45 patients (15.3%), the grade of the tumors is unknown. The tumor size was 0 to <5 cm in 54 cases (19.4%), 5-10 cm in 117 cases (41.9%) and >10 cm in 108 cases (38.7%). In 15 cases (5.1%), tumor size was unknown. Ninety-five patients (32.4%) were treated with adjuvant chemotherapy, and 125 patients (42.7%)) were treated with palliative chemotherapy. Prognostic factors influencing the overall survival were tumor size, grade, adjuvant radiotherapy and chemotherapy. Adjuvant radiotherapy had influence on disease-free survival. While tumor grade and size showed a significant value for predicting local recurrence, grade, localization of tumor, adjuvant chemotherapy and radiotherapy had an impact on metastasis development. The 1-year overall survival for all patients was 73.4%, 3-year overall survival was 51.8%, and 5-year overall survival was 45.1%.