Prognostic analysis of patients with operable gastric cancer and tolerability to adjuvant radio-chemo-therapy.

The aim of this study is to evaluate the tolerability and toxicity of adjuvant chemoradiotherapy (CRT) and to analyze the prognosis in patients with operable gastric cancer. The retrospective analysis included 723 patients with operable gastric cancer; stage IB-IV (M0), received adjuvant CRT from 8 Medical Centers in Turkey between 2003 and 2010. The patients' age, sex, tumor localization, Lauren classification, grade and stage of the disease, type of dissection, the toxicity and tolerability status and survival rate were analyzed. All patients were divided into two groups as tolerable group to adjuvant CRT and intolerable group to adjuvant CRT .Among the patient, 73.9% had stage III-IVM0 disease; 61.0% had the intestinal type of gastric cancer, 51.1% had the distal type, and 61.4% had undergone D2 dissections. The number of patients who completed the entire course of the adjuvant CRT was 545 (75.4%).The median follow-up period was 20.8 months (range: 1.5-107 months). Overall Survival (OS) rates were 80% and 52%, while the relapse free survival (RFS) rates were 75% and 48% at 1 and 3 years, respectively.In the univariate analysis of the groups based on the the age defined as <65 or ≥ 65 (p=0.16 / p=0.003), Lauren classification (p=0.004 / p<0.001), localization of tumor (p=0.02 / p=0.04), tumor grade (p=0.06 / p=0.003), disease stage (p<0.001 / p<0.001), type of dissection (p=0.445 / p=0.043), presence or absence of toxicity (p=0.062 / p=0.077) and tolerability of the therapy (p=0.002 / p=0.001). In the cox regression analysis, tumor stage (Hazard Ratio (HR): 0.332; 95% confidence interval (CI): 0.195-0.566; p<0.001), and tolerability (HR: 0.516; 95% CI: 0.305-0.872; p=0.014), were found to be related with the OS. Tumor stage (HR: 0.318; 95% CI: 0.190-0.533; p=<0.001) and tolerability (HR: 0.604; 95% CI: 0.367-0.995; p=0.048) were observed to be statistically significant in terms of the RFS.We have observed that whether a patient can or cannot tolerate adjuvant CRT due to its toxicity is an independent prognostic factor besides the known prognostic factors like tumor stage and Lauren classification. We are of the opinion that the treatment of patients who cannot tolerate adjuvant CRT should be replaced with less toxic adjuvant therapies.

Administration of contrast media just before cisplatin-based chemotherapy increases cisplatin-induced nephrotoxicity.

PURPOSE: There is a clinical need to predict the probability of cisplatin-induced nephrotoxicity (CIN) in order to make decisions about patient management and relevant preventive measures. The purpose of this study was to develop a risk prediction methodology of CIN. METHODS: 197 consecutive cancer patients, whose serum creatinine was measured at least 48 h before every cycle of cisplatin-based chemotherapy, were included in the study. Demographic and clinical data were collected from the patient medical records. Renal function was evaluated at least 48 h before treatment (day 0) of each cycle, based on the Modification of Diet in Renal Disease (MDRD) formula. CIN was defined as a decrease of ≥ 25% in glomerular filtration rate (GFR) compared to baseline GFR values. RESULTS: The mean age of the study population was 54.5±9.6 years. Fifty-eight patients (29.4%) whose GFR had decreased by at least 25% compared to baseline values formed the CIN group, and the remaining 139 patients formed the non-CIN group. No significant differences were noted between the CIN and non-CIN groups in terms of age, gender, body mass index and smoking history. Metastatic disease was similar in both groups (p=0.86). History of hypertension (p=0.81), diabetes mellitus (p=0.72), and cardiovascular disease (p=0.58) were similar in the two groups. Chemotherapeutic agents used concurrently with cisplatin were similar in both groups. Significantly more radiologic examinations using contrast media were performed in the CIN group compared with the non-CIN group (p=0.01). In patients exposed to contrast media within a week before cisplatin administration, the risk of CIN was 2.56-fold higher (957 percent; CI 1.28-5.11) than in patients without such exposure (p=0.009). CONCLUSION: In patients with exposure to contrast media within a week before cisplatin administration, the risk of CIN was significantly higher than in patients without such an exposure. No additional risk factors for CIN were found in this retrospective observational study.

Gemcitabine alone versus combination of gemcitabine and cisplatin for the treatment of patients with locally advanced and/or metastatic pancreatic carcinoma: a retrospective analysis of multicenter study.

The majority of patients with pancreatic cancer is of advanced disease. Several randomized Phase II and III trials suggest that the combination of gemcitabine and cisplatin (GemCis) response rates were higher than Gemcitabine (Gem) alone, however the trials were not enough powered to indicate a statistically significant prolongation of survival in patients with advanced pancreatic adenocarcinoma. The aim of this retrospective multicenter study is to evaluated the efficiency of Gem alone versus GemCis in patients with locally advanced and/or metastatic pancreatic adenocarcinoma .A total of 406 patients, from fourteen centers were evaluated retrospectively. All patients received Gem or GemCis as first-line treatment between September 2005 to March 2011. Primary end of this study were to evaluate the toxicity, clinical response rate, progression-free survival (PFS) and overall survival (OS) between the arms. There were 156 patients (M: 98, F: 58) in Gem arm and 250 patients (M: 175, F: 75) in the combination arm. Gemcitabin arm patients older than the combination arm ( median 63 vs 57.5, p=0.001). In patients with the combination arm had a higher dose reduction (25.2% vs 11.3%, p=0.001) and dose delay (34% vs 16.8%, p=0.001). Among patients with the combination and Gemcitabin arm gender, diabetes mellitus, performance status, cholestasis, grade, stage did not have a statistically difference (p>0.05). Clinical response rate to the combination arm was higher than the Gem arm (69.0% vs 49.7%, p=0.001). PFS was more favorable in the GemCis arm than Gem alone, but the difference did not attain statistical significance (8.9 vs 6.0, p=0.08). OS was not significantly superior in the GemCis arm (12.0 vs 10.2, p>0.05). Grade III-IV hematologic and nonhematologic toxicity were higher in the combination arm. PFS was more favorable in the GemCis arm than Gem alone, but the difference did not attain statistical significance. OS was not significantly superior in the GemCis arm.

Adjuvant therapy for gallbladder and bile duct cancers: retrospective comparative study.

PURPOSE: To study the efficacy of adjuvant therapy (chemotherapy and radiotherapy) in early stages (I-III) of gallbladder and bile duct cancers. METHODS: The clinical and pathological characteristics, treatment details and survival data of patients operated with early stages (I-III) of gallbladder and bile duct cancers and followed up in our clinic between August 2002 - November 2009 were retrospectively evaluated. RESULTS: 52 patients (median age 64 years) with early stages of gallbladder (n=36) and bile duct (n=16) cancers were analysed. Twenty-three (44.2%) patients had stage I, 23 (44.2%) stage II, and 6 (11.5%) stage III cancers. Approximately half of the patients (n=25; 48.1%) received postoperative adjuvant chemotherapy and/or radiotherapy. Patients with adjuvant treatment were younger than those without (62 vs. 71 years, p=0.06). Eighteen patients received chemotherapy alone, 2 chemotherapy followed by radiotherapy, 1 chemotherapy concurrently with radiotherapy, and 4 radiotherapy alone as adjuvant therapy. The regimen most frequently used (57.1%) was CFF (cisplatin 50 mg/m(2), day 1; folinic acid 200 mg/m(2), day 1; 5-fluorouracil [5-FU] 400 mg/m(2) bolus day 1 and 1600 mg/m(2) 48h continuous infusion). Some poor prognostic factors like high tumor grade and vascular invasion were more frequent in patients who received adjuvant therapy. The median disease free survival (DFS) was 11.4 months for the patients that received adjuvant therapy vs. 8.2 months for those without adjuvant therapy (p=0.67). During follow up 11 patients (44.0%) with adjuvant therapy and 12 (44.4%) without have died (p=0.97). The estimated median survival was 29 months. CONCLUSION: Although previous studies had shown that 5-FU-based adjuvant chemotherapy may provide a small survival advantage, this was not confirmed in the present study. Prospective adjuvant trials with a standard chemotherapy regimen and larger numbers of patients are required.

Gastric adenocarcinoma under the age of 40; more metastatic, less differentiated.

PURPOSE: Gastric carcinoma is relatively rare under the age of 40 years, and the mean age at presentation is 65 years. Histologically, adenocarcinoma prevails. Previous studies state that gastric adenocarcinoma under 40 is more aggressive. The present retrospective study was undertaken to clarify the clinicopathological characteristics of gastric adenocarcinoma in patients under 40 and to compare their clinical features with the patients over 40 years of age. METHODS: All of the patients with histologically diagnosed gastric adenocarcinoma who had applied to our department from March 2001 to September 2009 were retrospectively evaluated. Patients were stratified according to their age at diagnosis (≤ 40 years; group 1, and > 40 years; group 2). Their clinical, laboratory, and pathological characteristics were analyzed. RESULTS: 251 patients were studied. Sixty-eight percent of those under 40 and 46% over 40 had poorly differentiated histology (p= 0.036). Fifteen (60%) patients under 40 and 73 (32.3%) over 40 had metastatic diseases (p=0.007). CONCLUSION: Younger patients with gastric adenocarcinoma have less differentiated, more advanced and metastatic disease. Patients' complaints, tumor localization, metastatic sites and smoking did not differ significantly between the groups. Controversy for survival parameters still exists.

First-line therapy for metastatic colorectal carcinoma: modified FOLFOX4 or FOLFIRI-bevacizumab.

PURPOSE: The aim of this study was to compare the efficacy and toxicity of modified (m) FOLFOX4 (folinic acid, 5-fluorouracil [5-FU], and oxaliplatin) vs. FOLFIRI-B (folinic acid, 5-FU, irinotecan, and bevacizumab) as first-line treatment of metastatic colorectal carcinoma (MCRC). METHODS: The medical records of 89 MCRC patients treated with either mFOLFOX4 (group 1) or FOLFIRI-B (group 2) as first-line chemotherapy were evaluated retrospectively. RESULTS: Complete (CR) plus partial response (PR) were seen in 18 (36.7%) vs. 13 (32.5%) patients in the mFOLFOX4 vs. FOLFIRI-B, respectively (p=0.67). Median progression-free survival (PFS) was 9 months (95% CI 7.2- 9.5) vs. 10 months (95% CI 7.6-12.3) in group 1 vs. group 2, respectively (p=0.30). Median overall survival (OS) was 22 months (95% CI 17.6-26.3) and 19 months (95% CI 13-24.9) in group 1 and 2, respectively (p=0.32). There was no statistically significant difference in grade 3-4 hematological toxicity between the groups, but grade 3-4 grade weakness, diarrhea, nausea and vomiting was observed more frequently in the FOLFIRI-B patients (p=0.03, p=0.01, p=0.05, respectively). CONCLUSION: Our data suggest that mFOLFOX4 and FOLFIRI-B are equally effective as first-line chemotherapy in MCRC patients. This may partially be explained by the fact that almost 50% of those receiving FOLFOX in the first-line received FOLFIRI-B in the second-gline, an observation suggesting that bevacizumab in the second line may be as effective as in the first line.

Mitomycin-C in combination with fluoropyrimidines in the treatment of metastatic colorectal cancer after oxaliplatin and irinotecan failure.

PURPOSE: To retrospectively evaluate the efficacy and tolerability of mitomycin-C (MMC) in combination with fluoropyrimidines as salvage 3rd -or 4th-line therapy in metastatic colorectal cancer (MCRC) patients. METHODS: All patients in this study had previously failed oxaliplatin and irinotecan-based chemotherapy. Patients were treated with MMC (6 mg/m(2) intravenously/i.v.) on day 1 in combination with either oral UFT (500 mg/m(2)) and oral leucovorin (LV) (30 mg) on days 1-14 every 3 weeks (group A) or infusional 5-fluorouracil (5-FU) by deGramont regimen with i.v. LV (200 mg/m(2)) on days 1 and 2, every 2 weeks (group B). RESULTS: Thirty-nine MCRC patients were analyzed. Twenty-two of them were in group A and 17 in group B. Thirty-three were evaluable for clinical efficacy. The clinical benefit in the intent-to-treat (ITT) population was 30.8%. Median progression free survival (PFS) was 6 months (95% confidence interval/ CI 4-8) and median overall survival (OS) 9 months (95% CI 6.5-11.5). Median PFS was 3 months (95% CI 2.4-3.6) in group A and 7 months (95% CI 5.1-8.9) in group B (p=0.009). Median OS was 7 months (95% CI 4.3-9.7) in group A and 12 months (95% CI 5.4-18.6) in group B (p=0.422). The combination of MMC and fluoropyrimidines was generally well tolerated. The most common severe toxicities were nausea and vomiting, neutropenia, hepatotoxicity and diarrhea. CONCLUSION: MMC in combination with fluoropyrimidines is safe and active in heavily-pretreated MCRC patients. This combination remains a viable option in these patients. However, better therapies are urgently needed.

Good tolerance of weekly irinotecan in a patient with metastatic colorectal cancer on chronic hemodialysis.

Pharmacokinetic properties of many antineoplastic agents or their metabolites change with organ dysfunction. Unfortunately, chemotherapy doses determined in phase I and II studies in patients with normal hepatic and renal reserves are not usually applicable to those with hepatic and/or renal dysfunction. Considering the high incidence of colorectal adenocarcinoma, it is not unusual for a colorectal cancer patient to be on chronic hemodialysis. We report a patient with metastatic colorectal cancer on chronic hemodialysis who tolerated weekly irinotecan at 50 mg/m2 well without significant toxicity. We briefly discuss therapeutic dose modification in such patients.