Efficacy and safety of TC dose-dense chemotherapy as first-line treatment of epithelial ovarian cancer: a single-institution retrospective cohort study.

BACKGROUND: The optimal first-line therapy of advanced ovarian cancer still remains questionable: standard paclitaxel-carboplatin (TC), dose-dense TC, intraperitoneal chemotherapy or TC plus bevacizumab. In this study, we present the real-life results of dose-dense treatment of the single-institution on Caucasian population. METHODS: A retrospective cohort study was used on consecutive samples of 74 patients treated with the conventional 3-weekly TC protocol (2008-11) and on 70 treated with TC dose-dense protocol (2012-16). The primary endpoint of this study was overall survival (OS). Secondary endpoints were progression free-survival (PFS) and toxicity. We made adjustments for age, pathohistological type, tumor grade, stage and postoperative residual disease by Cox regression. RESULTS: After adjustment for pre-planned clinical and sociodemographic factors, patients treated with dose-dense protocol showed a significantly lower hazard for dying from any cause, than patients treated with conventional protocol (HR = 0.50; 95% CI 0.26-0.98; P = 0.042). Median OS, at 60 months follow-up had not been reached in the dose-dense group, while in the standard treatment group was 48 months (95% CI 33-62). Unadjusted PFS was significantly longer in the dose-dense group (HR = 0.58; 95% CI 0.38-0.88; P = 0.011), but not after the adjustment (P = 0.096). Generally, the level of toxicity was similar in both groups of patients. The need for blood transfusions and usage of filgrastim was significantly higher in the TC dd group. The incidence of neutropenia and thrombocytopenia Grade 3 or 4 were not significantly different in both regimens. CONCLUSIONS: Our retrospective study has shown the superior efficacy and comparable toxicity of dose-dense chemotherapy regimen over the conventional regimen in treatment of ovarian cancer on Caucasian population at a single-institution.

Prognostic significance of MAPK, Topo IIα and E-cadherin immunoexpression in ovarian serous carcinomas.

Ovarian cancer accounts for only 3% of all cancers in women but is the most lethal gynaecologic malignancy. Low-grade and high-grade ovarian serous carcinomas (OSCs) represent two different diseases with different prognosis, approaches to detection and treatment. We assessed correlation between, MAPK, topoIIα, E-cadherin immunoexpression and clinicopathological features with overall survival (OS) in OSCs. The study included 81 patients undergoing surgery between January 1995 and December 2005.Formalin fixed paraffin embedded tumour sections were reviewed and examined immunohistochemically using antibodies against MAPK, topoIIα and E-cadherin. The clinicopathological features included: age at surgery, stage according to the criteria of the International Federation of Gynecology and Obstetrics (FIGO), tumour grade, residual disease and vascular invasion. Only ten patients (12.3%) were diagnosed in early FIGO stage of disease. According to morphological criteria, 13.6% of tumor samples were low-grade OSCs and 86.4% were high-grade OSCs. On uninominal analysis, residual disease (p<0.001), E-cadherin (p<0.001), vascular invasion (p=0.002), high-grade morphology (p=0.025) and FIGO stage III-IV (p=0.010) were related to significantly shorter OS. We found no significant association between, MAPK and topoIIα expression and OS. Multinominal analysis revealed that only residual disease (p<0.001) and negative E-cadherin immunoexpression were useful independent predictors of unfavourable clinical outcome and shorter OS.

Optimisation of breast cancer patients' follow-up - potential way to improve cancer care in transitional countries.

The aim of this analysis was to evaluate adherence of Croatian oncologists to follow-up criteria as suggested by the current national and international guidelines for women with breast cancer receiving adjuvant endocrine therapy. The use of clinical and diagnostic methods was documented in this prospective, non-interventional, multicenter study. A total of 438 post-menopausal patients receiving adjuvant endocrine treatment with non-steroidal aromatase inhibitors were included. Average annual frequency for each clinical and diagnostic method was calculated. Median adjuvant endocrine treatment duration before study recruitment was 10.5 months (interquartile 4.7-26.6). Patients were followed up for an average 23.5 ± 4.9 months. Average number of oncological visits was 5.3. Mammograms were performed at mean annual frequency of 0.7, chest radiographs at 0.5, abdominal ultrasounds at 0.9, breast ultrasounds at 1.2, complete blood counts and chemistry panels at 1.7, carcinoembryonic antigen at 0.8, cancer antigen 15-3 at 1.6, gynaecological examination at 0.3, and densitometry at mean annual frequency of 0.3. In conclusion, among post-menopausal women with breast cancer receiving adjuvant endocrine therapy in this study, more unnecessary and unproven follow-up procedures were done compared to the guidelines' recommendations.

Final results of the TANIA randomised phase III trial of bevacizumab after progression on first-line bevacizumab therapy for HER2-negative locally recurrent/metastatic breast cancer.

BACKGROUND: The randomised phase III TANIA trial demonstrated that continuing bevacizumab with second-line chemotherapy for locally recurrent/metastatic breast cancer (LR/mBC) after progression on first-line bevacizumab-containing therapy significantly improved progression-free survival (PFS) compared with chemotherapy alone [hazard ratio (HR) = 0.75, 95% confidence interval (CI) 0.61-0.93]. We report final results from the TANIA trial, including overall survival (OS) and health-related quality of life (HRQoL). PATIENTS AND METHODS: Patients with HER2-negative LR/mBC that had progressed on or after first-line bevacizumab plus chemotherapy were randomised to receive standard second-line chemotherapy either alone or with bevacizumab. At second progression, patients initially randomised to bevacizumab continued bevacizumab with their third-line chemotherapy, but those randomised to chemotherapy alone were not allowed to cross over to receive third-line bevacizumab. The primary end point was second-line PFS; secondary end points included third-line PFS, combined second- and third-line PFS, OS, HRQoL and safety. RESULTS: Of the 494 patients randomised, 483 received second-line therapy; 234 patients (47% of the randomised population) continued to third-line study treatment. The median duration of follow-up at the final analysis was 32.1 months in the chemotherapy-alone arm and 30.9 months in the bevacizumab plus chemotherapy arm. There was no statistically significant difference between treatment arms in third-line PFS (HR = 0.79, 95% CI 0.59-1.06), combined second- and third-line PFS (HR = 0.85, 95% CI 0.68-1.05) or OS (HR = 0.96, 95% CI 0.76-1.21). Third-line safety results showed increased incidences of proteinuria and hypertension with bevacizumab, consistent with safety results for the second-line treatment phase. No differences in HRQoL were detected. CONCLUSIONS: In this trial, continuing bevacizumab beyond first and second progression of LR/mBC improved second-line PFS, but no improvement in longer term efficacy was observed. The second-line PFS benefit appears to be achieved without detrimentally affecting quality of life. CLINICALTRIALSGOV: NCT01250379.

Retrospective analysis of efficacy of trastuzumab in adjuvant treatment of HER 2 positive early breast cancer - single institution experience.

Addition of trastuzumab to chemotherapy is the cornerstone of adjuvant treatment of early HER2 positive breast cancer. Clinical trials and metaanalyses of adjuvant trastuzumab have shown significant reduction in risk of recurrence and death. Nevertheless, the real magnitude of the effect of any drug must be reevaluated in daily clinical conditions, due to the fact that daily clinical practice often differs from conditions in clinical trials. In order to measure the benefit of adding adjuvant trastuzumab in HER 2 positive early breast cancer treatment, we have performed retrospective analysis in a single institution on consecutive patients divided in 2 cohorts: one, treated in "pre - trastuzumab" and the other in "trastuzumab era". Between 2003 and 2012, 258 consecutive HER 2 positive patients with early breast cancer have been treated with adjuvant chemotherapy, 103 patients did not received trastuzumab (patients treated from 2003 till 2007), and 155 (patients treated from 2008 till 2012) received trastuzumab. Patients who received trastuzumab experienced significantly longer median disease-free survival (107 vs. 92 months, LR: 11.6, p <0.001); breast cancer-specific survival (130 vs. 117 months, LR: 10.7, p < 0.001) and median overall survival (123 vs. 108 months LR = 11.6, p < 0.001). The benefits of adding trastuzumab were independent of chemotherapy regimen and hormonal therapy. This retrospective analysis has shown a clear, statistically significant benefit of adjuvant trastuzumab in treatment of early, HER2 positive breast cancer in daily clinical practice, and confirmed the results of the registration clinical trials.

Guidelines for the prevention, detection and therapy of vitamin d deficiency in adults

It is estimated that over one billion of people around the globe have low serum values of vitamin D, therefore, we can consider vitamin D deficiency as a pandemic and public health problem. Geographic position of Croatia, especially the continental part of the country, is a risk factor for the development of deficiency of vitamin D in the population. The aim of these guidelines is to provide the clinicians with easy and comprehensive tool for prevention, detection and therapy of vitamin D deficienney in healthy population and various groups of patients. They were made as a result of collaboration of clinicians of different backgrounds who are dealing with patients at risk of vitamin D deficiency. These guidelines are evi- dence-based, according to GRADE-system (Grading of Recommendations, Assessment, Development and Evaluation), which describes the level of evidence and strength of recommendation. The main conclusions address the recommended serum vitamin D values in the population which should be between 75 and 125 nmol/L and defining recommended preven- tive and therapeutic dosages of vitamin D in order to reach the adequate levels of serum vitamin

Pharmacoeconomic and clinical implications of sequential therapy for metastatic renal cell carcinoma patients in Central and Eastern Europe.

INTRODUCTION: The incidence and mortality rates of kidney cancer in the Central and Eastern European (CEE) region are among the highest in the world. Access to second and subsequent lines of metastatic renal cell carcinoma (mRCC) therapies is highly varied in the region. Despite the increasing body of evidence supporting the clinical benefit of multiple lines of treatment, access to treatment beyond first line is restricted in many of these countries. AREAS COVERED: The adoption of targeted therapies for the first-line treatment of mRCC in the region was slow and faced many obstacles. In order to evaluate the current status of treatment beyond the first-line setting in the CEE region, this review examines the availability and reimbursement of mRCC drugs and clinical practice in institutions that treat patients with mRCC. EXPERT OPINION: This review highlights the need to raise awareness among physicians, payers and regulators on clinical trial and cost-effectiveness data regarding the treatment of mRCC beyond the first line. The obstacles to mRCC drug access highlighted in this review need to be overcome to ensure that patients are receiving the best treatment available.

Final results from the large sunitinib global expanded-access trial in metastatic renal cell carcinoma.

BACKGROUND: We report final results with extended follow-up from a global, expanded-access trial that pre-regulatory approval provided sunitinib to metastatic renal cell carcinoma (mRCC) patients, ineligible for registration-directed trials. METHODS: Patients ⩾18 years received oral sunitinib 50 mg per day on a 4-weeks-on-2-weeks-off schedule. Safety was assessed regularly. Tumour measurements were scheduled per local practice. RESULTS: A total of 4543 patients received sunitinib. Median treatment duration and follow-up were 7.5 and 13.6 months. Objective response rate was 16% (95% confidence interval (CI): 15-17). Median progression-free survival (PFS) and overall survival (OS) were 9.4 months (95% CI: 8.8-10.0) and 18.7 months (95% CI: 17.5-19.5). Median PFS in subgroups of interest: aged ⩾65 years (33%), 10.1 months; Eastern Cooperative Oncology Group performance status ⩾2 (14%), 3.5 months; non-clear cell histology (12%), 6.0 months; and brain metastases (7%), 5.3 months. OS was strongly associated with the International Metastatic Renal-Cell Carcinoma Database Consortium prognostic model (n=4065). The most common grade 3/4 treatment-related adverse events were thrombocytopenia (10%), fatigue (9%), and asthenia, neutropenia, and hand-foot syndrome (each 7%). CONCLUSION: Final analysis of the sunitinib expanded-access trial provided a good opportunity to evaluate the long-term side effects of a tyrosine kinase inhibitor used worldwide in mRCC. Efficacy and safety findings were consistent with previous results.

Insights into cancer surveillance in Central and Eastern Europe, Israel and Turkey.

The current cancer landscape within transitional economies in central and Eastern Europe and the Mediterranean area is not particularly optimistic. Current perceptions are often based on extrapolations from other countries and regions; and hence the authors collaborated with the South Eastern Europe Oncology Group (SEEROG) to collect information on cancer registration in Central and Eastern Europe, Israel and Turkey. Healthcare authorities and specialist oncology centres in 21 countries in the region were contacted for information on cancer registries in their countries. Based on this information, the authors believe that the recording and reporting of data on cancer in the region is at an acceptable level. The authors discuss and compare institution- and population-based registries, and present opinions on elements of an 'ideal registry' based on the survey replies and comparisons with other registries. A comparison with the sources used for GLOBOCAN 2008 illustrates the need for consistent data to be communicated, published and utilised throughout the region and the oncology community. The authors conclude by considering the potential value of collaboration between health authorities across the region, as well as between the clinical and epidemiological communities, to ensure that cancer data are consistently collected, verified and made public.

First-line treatment of advanced ovarian cancer with paclitaxel/carboplatin with or without epirubicin (TEC versus TC)--a gynecologic cancer intergroup study of the NSGO, EORTC GCG and NCIC CTG.

BACKGROUND: The addition of anthracyclines to platinum-based chemotherapy may provide benefit in survival in ovarian cancer patients. We evaluated the effect on survival of adding epirubicin to standard carboplatin and paclitaxel. PATIENTS AND METHODS: We carried out a prospectively randomized phase III study comparing carboplatin plus paclitaxel (TC; area under the curve 5 and 175 mg/m(2)) with the same combination and epirubicin (TEC; 75 mg/m(2) i.v.). Between March 1999 and August 2001, 887 patients with epithelial ovarian, tubal or peritoneal cancer International Federation of Gynecology and Obstetrics stages IIB-IV were randomized to receive either TC (442 patients) or TEC (445 patients). RESULTS: Median time to progression was 16.4 months in the TEC arm and 16.0 months in the TC arm (hazard ratio 0.99; 95% confidence interval [CI]: 0.9-1.2). Median overall survival time was 42.4 months for the TEC arm and 40.2 for the TC arm (hazard ratio 0.96; 95% CI: 0.8-1.1). Grade 3/4 hematologic toxic effects and most grade 3/4 non-hematologic toxic effects were more frequent in the TEC arm. Accordingly, a quality-of-life analysis showed inferiority of TEC versus TC. CONCLUSION: The addition of epirubicin to standard carboplatin and paclitaxel treatment did not improve survival in patients with advanced ovarian, tubal or peritoneal cancer.

Lapatinib in the treatment of HER-2 overexpressing breast cancer.

Lapatinib is the only clinically available agent for the treatment of patients with human epidermal growth factor receptor-2 (HER-2) positive tumors that have progressed on treatment with trastuzumab, taxanes and anthracyclines. Moreover, when given with letrozole in postmenopausal patients with estrogen receptor (ER) and HER-2 positive disease it induces clinically meaningful benefit. Recently presented neoadjuvant data suggests an important place for the combination of trastuzumab and lapatinib in the therapy of early HER-2 positive breast cancer. This article reviews the current status and future perspectives of lapatinib.

Combination of capecitabine and mitomycin C as first-line treatment in patients with metastatic breast cancer.

Optimal first-line chemotherapy for metastatic breast cancer (MBC) is challenging, particularly in patients previously treated with (neo) adjuvant anthracyclines/taxanes. Based on preclinical synergy with mitomycin C (MMC) and capecitabine in human tumor xenografts, we conducted a phase II study of first-line capecitabine and MMC in MBC. Patients received 3-weekly chemotherapy comprising MMC 8 mg/m² day 1 and capecitabine 1000 mg/m² twice daily, days 1-14. Combination chemotherapy was administered for a maximum six cycles, single-agent capecitabine could be continued until progressive disease or unacceptable toxicity. Thirty patients were included, objective response rate was 65.5%. After a median follow-up of 18.5 months, median time to progression was 8.5 months and median overall survival was 29.8 months. The main adverse events were thrombocytopenia, pneumonitis and hemolytic uremic syndrome. Our data suggest that first-line capecitabine and MMC has good antitumor activity in MBC, but is associated with MMC-specific toxicity.

Capecitabine and mitomycin-C in the therapy of pretreated patients with metastatic colorectal cancer: single center retrospective study with 36 patients.

PURPOSE: To evaluate the therapeutic effectiveness and safety of treatment with capecitabine and mitomycin-C (MMC) in patients with metastatic colorectal cancer previously treated with at least one chemotherapy regimen for recurrent or metastatic disease. PATIENTS AND METHODS: A total of 36 patients (male/female 21/15, median age 62.5 years) with metastatic colorectal cancer were treated with capecitabine and MMC as their second, third or fourth line chemotherapy regimen. Chemotherapy consisted of intravenous MMC 6 mg/m(2) on day 1 plus oral capecitabine 1000 mg/m(2) twice daily on days 1-15 followed by 7-day rest. Treatment courses were repeated every 3 weeks unless there was evidence of progressive disease or unacceptable toxicity. RESULTS: All 36 patients were evaluable for toxicity and response. A total of 175 cycles were administered (median 4.86, range 3-6). Two (5.6%) patients achieved complete response, 3 (8.3%) partial response, 14 (38.9%) had stable disease and 16 (44.4%) patients progressed. Median time to tumor progression (TTP) was 4.5 months and median overall survival (OS) 13 months. No toxic deaths occurred. Toxicity was mild and easily manageable. CONCLUSION: This retrospective study demonstrated that the combination of capecitabine and MMC is an effective and well-tolerated regimen for patients previously treated for metastatic or recurrent colorectal cancer.

Microsatelite GT polymorphism in the toll-like receptor 2 is associated with colorectal cancer.

Factors underlying genetic predisposition for development of sporadic colorectal cancer are largely unknown. The fact that this cancer is more common in patients suffering from inflammatory bowel disease raises the question of the relationship between chronic inflammation and cancer. Toll-like receptors 2 (TLR2) and 4 (TLR4) are critical in initiating innate immune response and inflammation toward various bacteria commonly found in the intestine. Recent evidence about the association of polymorphisms in these genes with ulcerative colitis and Crohn's disease, as well as other inflammatory conditions, was the basis for our investigation of their role in sporadic colorectal cancer. We assessed genotype and allele frequencies of TLR2 GT microsatelite polymorphism, TLR2 Arg753Gln, TLR4 Asp299Gly and TLR4 Thr399Ile polymorphisms in 89 colorectal cancer patients and 88 age- and sex-matched controls. The frequency of TLR2 GT microsatelite alleles with 20 and 21 GT repeats was decreased (p = 0.0044 and p = 0.001, respectively), while the frequency of the allele with 31 GT repeats was increased (p = 0.0147) in patients. The mutant allele Asp299Gly of TLR4 gene was slightly more frequent in colorectal cancer patients (p = 0.0269). In conclusion, we report an association of microsatelite GT polymorphisms of TLR2 gene and Asp299Gly polymorphism of the TLR4 gene with sporadic colorectal cancer among Croatians.

Drug-induced hepatitis in a patient with malignant melanoma treated with interferon alfa 2b adjuvantly who had been administered gemfibrozil in therapy.

A well-known side effect of chemotherapy, covering a wide range of drugs, is drug-induced hepatitis. We are reporting on a 61-yr-old female patient whose malignant melanoma had been surgically removed, and on whom adjuvant therapy with interferon alfa 2b was initiated. The patient had mild hyperlipidemia, of which she had been aware for several years, but which had gone untreated with medicinal intervention. After the patient was started on interferon alfa therapy, continuously increasing values of triglyceride were measured. Therefore, 3 mo after the introduction of adjuvant therapy, gemfibrozil was prescribed at a dose of 600 mg per day. Within a few days after the patient had been taking this combined therapy, the clinical and laboratory values of drug-induced hepatitis developed. Soon after discontinuance of treatment by both drugs, the signs and symptoms of hepatitis disappeared. Adjuvant interferon therapy was not continued afterward owing to the patient's wish. We do not know if the hepatitis was the side effect to gemfibrozil alone, or the side effect was a result of an interaction between the two drugs. As far as we could find, this is the first case report of possible negative interaction between interferon alfa 2b and gemfibrozil. Our intention in this article is to point out that prescription of any drugs, especially new ones, should be balanced and carefully monitored because of possible side effects.

Concomitant chemobrachyradiotherapy with ifosfamide and cisplatin followed by consolidation chemotherapy in the treatment of locally advanced adenocarcinoma or adenosquamous carcinoma of the cervix uteri.

The optimal treatment of women with locally advanced adenocarcinoma or adenosquamous carcinoma of the cervix uteri is still undefined. We report a series of four consecutive patients with locally advanced adeno- or adenosquamous carcinomas of the uterine cervix (FIGO Stages IB-IIIB) treated by concomitant chemobrachyradiotherapy with ifosfamide and cisplatin followed by one to four cycles of consolidation chemotherapy with the same drug combination. After completion of this treatment all patients showed complete clinical remission. Now, after a median follow-up of 40 (range: 13.5-61) months all patients still present with no evidence of disease. Despite the low number of patients in this series we may conclude that concomitant chemobrachyradiotherapy with ifosfamide and cisplatin followed by consolidation chemotherapy with the same drug combination is an efficacious treatment of patients with locally advanced adeno- or adenosquamous carcinomas of the cervix uteri.

Long-lasting complete remission of a patient with cervical cancer FIGO IVB treated by concomitant chemobrachyradiotherapy with ifosfamide and cisplatin and consolidation chemotherapy--a case report.

The treatment of women with already metastasized cervical cancer at initial diagnosis represents a challenge to gynecologic oncologists. We report on a 63-year-old patient with locally advanced squamous cell carcinoma of the cervix uteri with an isolated metastasis to the left ovary. Following treatment with concomitant chemoradiotherapy with ifosfamide and cisplatin and three cycles of consolidation chemotherapy with the same drug combination a complete clinical remission could be documented. At present, 35 months after her disease was diagnosed, she is still without any evidence of disease. The very promising outcome of this patient might suggest that combined chemoradiation which is the standard treatment of locally advanced cervical cancer is justified as well in the metastatic setting, provided the metastatic lesion is covered within the usual radiation field.

First-line treatment of ovarian cancer FIGO stages IIb-IV with paclitaxel/epirubicin/carboplatin versus paclitaxel/carboplatin.

The objective of this study was to compare the safety and efficacy of carboplatin plus epirubicin and paclitaxel (TEC) to carboplatin and paclitaxel (TC), in the treatment of epithelial ovarian, peritoneal, or tubal carcinoma. Between March 1999 and August 2001, 887 patients were randomized to receive six to nine cycles of paclitaxel (175 mg/m2, 3 h intravenously) followed by carboplatin (AUC 5, Calvert formula) with or without epirubicin (75 mg/m2 intravenously prior to paclitaxel), on a 3-weekly schedule. The primary endpoint was progression-free survival. Demographic information: Residual disease <1 cm was reported on 41% of patients. At the end of treatment, 65% in the TEC and 55% in the TC arm had achieved a clinical complete response, and 18 and 25% a clinical partial response resulting in an overall response rate of 83% in the TEC and 80% in the TC arm, whereas 7 and 9% had progressive disease, respectively. The three-drug combination produced a markedly higher myelotoxicity, resulting in a higher frequency of febrile neutropenia (12.5% of the TEC and 1.5% of the TC patients) and a higher number of dose reductions and treatment delays. Cycle prolongation above seven days was seen in 7 and 5% of cycles in the TEC and TC arm, respectively. Stomatitis > or = grade 3 was also higher with TEC (4% TEC and 0.5% TC). Reductions in left ventricular ejection fraction of more than 15% after six courses were slightly more common with the TEC regimen (3% versus 1.5%), but the difference was not statistically significant (P = 0.2). In conclusion, treatment with the TEC combination produced a higher rate of complete responses than treatment with the TC combination. Toxicity was manageable. Long-term survival data are awaited.

Current state-of-the-art of concomitant chemoradiation in cervical carcinomas.

Despite screening programs, cervical carcinoma remains a major health problem throughout the world. Until recently pelvic radiation has been the standard therapy for advanced disease with overall five-year survival rates of 50%. Recently, five randomized trials demonstrated a significant survival advantage for the concomitant administration of radiotherapy and cisplatin-based chemotherapy. Although the trials vary somewhat in terms of stage of disease, dose of radiation, and schedule of radiation and cisplatin, they all demonstrated a significant survival benefit for the combined approach. Congruent to these findings are results from a meta-analysis based on the data from 19 trials with 4,580 randomized patients. The absolute increase in progression-free and overall survival was 16% and 12%, respectively. Contrary to these findings is the result of the National Cancer Institute of Canada (NCCI) trial. Despite that result cisplatin-based concomitant chemoradiotherapy has become the standard treatment of locally advanced cervical cancer.

WR-2721 reduces intestinal toxicity from concurrent gemcitabine and radiation treatment.

BACKGROUND: The nucleoside analog gemcitabine is a potent radiosensitizer of both tumor and normal mucosa, so severe toxic reactions have resulted from its combination with radiation in some clinical treatment schedules for pancreatic cancer. WR-2721 (amifostine) has been shown to reduce normal tissue toxicity produced from both radiation treatment and some chemotherapeutics. The aim of this study was to determine if WR-2721 can protect the gastrointestinal mucosa from injury by concurrent gemcitabine and radiation treatment. METHODS AND MATERIALS: Gemcitabine was injected ip into C3Hf/Kam mice at a concentration of 33 mg/kg 24 h before whole-body irradiation. A single dose (200 mg/kg) of WR-2721 was given 30 min before the radiation treatment or 30 min before gemcitabine or at both times. A quantitative assessment of the chemotherapy/radiation-induced damage was carried out using the mouse microcolony assay for stem cell survival in the intestinal crypts. RESULTS: WR-2721 given 30 min before gemcitabine followed 24 h later by radiation did not confer any protection to the jejunum (DMF 0.95). However, WR-2721 administered 30 min before radiation without or with prior gemcitabine produced protection factors (PF) of 1.35 and 1.42 CONCLUSIONS: WR-2721 did not directly protect the gastrointestinal mucosa from gemcitabine toxicity, but it did protect the gemcitabine-radiosensitized mucosa from acute radiation damage by a factor of 1.42. Therefore, in clinical treatment protocols using concurrent chemoradiation with gemcitabine, WR-2721 may have clinical utility in protecting against radiation-induced mucosal toxicity.