Difference In Gastrointestinal Toxicity Research Articles

The incidence rate of allergic reactions induced by oxaliplatin is higher in patients with rectal cancer compared with colon cancer

Aim To explore the diverse profiles of adverse reactions caused by oxaliplatin between colon and rectal cancer, we investigated the toxicity of oxaliplatin in patients with colon and rectal cancer. Methods From January 2017 to December 2021, 200 cases of sporadic CRC patients with adverse reactions after oxaliplatin were collected from Harbin Medical University Cancer Hospital, Harbin, China. All patients received a chemotherapy regimen containing oxaliplatin (100 colon cancer and 100 rectal cancer). We reviewed the adverse reactions induced by oxaliplatin in patients with colon and rectal cancer. Results We found there was no significant difference in gastrointestinal toxicity, hematotoxicity, neurotoxicity, hepatotoxicity, respiratory toxicity, and cardiotoxicity caused by oxaliplatin between patients with colon cancer and patients with rectal cancer, but patients with rectal cancer were more prone to allergic reactions than patients with colon cancer after oxaliplatin. In addition, we found neutrophil-to-lymphocyte ratios (NLR) and platelet-to-lymphocyte ratios (PLR) were higher in patients with colon cancer than in patients with rectal cancer. This may reflect differences in immune status and inflammatory responses between colon cancer and rectal cancer, which might be the reason for more allergic reactions caused by oxaliplatin in colon cancer patients compared to rectal cancer patients. Conclusion Except for a higher incidence of allergic reactions in patients with rectal cancer, no significant difference in the incidence of adverse drug reactions associated with oxaliplatin was noted between patients with colon cancer and rectal cancer. Our results suggested more attention should be paid to the allergic reaction caused by oxaliplatin in patients with colon cancer.

A retrospective study of locally advanced cervical cancer cases treated with CT-based 3D-IGBT compared with 2D-IGBT.

To retrospectively review locally advanced cervical cancer (CC) cases treated with three-dimensional image-guided brachytherapy (3D-IGBT) and two-dimensional (2D)-IGBT. Patients with Stage IB-IVa CC who underwent intracavitary irradiation between 2007 and 2021 were divided into the 3D-IGBT and 2D-IGBT groups. Local control (LC), distant metastasis-free survival (DMFS), progression-free survival (PFS), overall survival (OS), and gastrointestinal toxicity (G3 or more) were investigated at 2/3years post-treatment. Seventy-one patients in the 2D-IGBT group from 2007 to 2016 and 61 patients in the 3D-IGBT group from 2016-2021 were included in the study. The median follow-up period was 72.7 (4.6-183.9) months in the 2D-IGBT group and 30.0 (4.2-70.5) months in the 3D-IGBT group. The median age was 65.0 (40-93) years in the 2D-IGBT group and 60.0 (28-87) years in the 3D-IGBT group, but there was no difference in FIGO stage, histology, or tumor size between the groups. In treatment, the median A point dose was 56.1 (40.0-74.0) Gy in the 2D-IGBT group and 64.0 (52.0-76.8) Gy in the 3D-IGBT group (P < 0.0001), and the proportion of patients who underwent chemotherapy more than five times was 54.3% in the 2D-IGBT group and 80.8% in the 3D-IGBT group (P = 0.0004). The 2/3-year LC, DMFS, PFS, and OS rates were 87.3%/85.5%, 77.4%/65.0%, 69.9%/59.9%, and 87.9%/77.9% in the 2D-IGBT group, and 94.2%/94.2%, 81.8%/81.8%, 80.5%/80.5%, and 91.6%/83.0% in the 3D-IGBT group, respectively. A significant difference was observed in PFS (P = 0.02). There was no difference in gastrointestinal toxicity, but there were four intestinal perforations in the patients from the 3D-IGBT group, three of whom had a history of bevacizumab treatment. The 2/3-year LC of the 3D-IGBT group was excellent and PFS also tended to improve. Care should be taken with concomitant use of bevacizumab after radiotherapy.

Chronomodulated Administration of Chemotherapy in Advanced Colorectal Cancer: A Systematic Review and Meta-Analysis.

In this systematic review, the efficacy and safety of chronomodulated chemotherapy, defined as the delivery of chemotherapy timed according to the human circadian rhythm, were assessed and compared to continuous infusion chemotherapy for patients with advanced colorectal cancer. Electronic English-language studies published until October 2020 were searched. Randomised controlled trials (RCTs) comparing chronomodulated chemotherapy with non-chronomodulated (conventional) chemotherapy for the management of advanced colorectal cancer were included. The main outcomes were the objective response rate (ORR) and system-specific and overall toxicity related to chemotherapy. Electronic databases including Ovid Medline, Ovid Embase, Cochrane Central Register of Controlled Trials and the Cochrane Database of Systematic Review were searched. In total, seven RCTs including 1,137 patients were analysed. Males represented 684 (60%) of the study population. The median age was 60.5 (range = 47.2-64) years.There was no significant difference between chronomodulated and conventional chemotherapy in ORR (risk ratio (RR) = 1.15; 95% confidence interval (CI) = 0.87-1.53). Similarly, there was no significant difference in gastrointestinal toxicity under the random effect model (RR = 1.02; 95% CI = 0.68-1.51). No significant difference was found regarding neurological and skin toxicities (RR = 0.64, 95% CI = 0.32-1.270 and RR = 2.11, 95% CI = 0.33-13.32, respectively). However, patients who received chronomodulated chemotherapy had less haematological toxicity (RR = 0.36, 95% CI = 0.27-0.48). In conclusion, there was no overall difference in ORR or haematologic toxicity between chronomodulated and non-chronomodulated chemotherapy used for patients with advanced colorectal cancer. Chronomodulated chemotherapy can be considered in patients at high risk of haematological toxicities.

Dose-escalated neoadjuvant chemoradiotherapy for locally advanced oesophageal or oesophagogastric junctional adenocarcinoma.

BackgroundNeoadjuvant chemoradiotherapy with CROSS-protocol is the standard of care for locally advanced esophageal cancer. The purpose of this study was to demonstrate an improvement in complete pathological response (ypCR) after a dose-escalation neoadjuvant protocol compared to standard treatment. Secondary endpoints were disease-free survival (DFS) and acute gastrointestinal toxicity.Material and methodsWe prospectively evaluated patients with locally advanced esophageal adenocarcinoma who received neoadjuvant chemoradiotherapy. The radiation dose was 41.4 Gy in 23 fractions or 50.4 Gy in 28 fractions with weekly administration of six intravenous cycles of carboplatin AUC 2 mg/mL and intravenous paclitaxel 50 mg/m2 followed by surgery.ResultsBetween December 2015 and July 2020, 21 patients were treated according to the reported radiation schedules. Median age was 61 years (57–67). 20 (95.2%) tumors were located at the esophagogastric junction and 1 (4.8%) in the middle esophagus. Five (23.8%) were stage II and 16 (76.2%) stage III. Twelve (57.1%) patients received 41.4 Gy (standard group) and 9 (42.9%) received 50.4 Gy (intensification group), with 5 (41.67%) and 5 (55.6%) presenting ypCR in the standard and intensification group, respectively (p = 0.67). After a median follow-up of 17 months (8–30), DFS in the standard group was 17.78 months [95% (CI, confidence interval): 12.9–22.6] and 45.5 months (95% CI: 24.4–66.05) in the intensification group (p = 0.299). Grade III acute gastrointestinal toxicity was 16% and 33.33%, respectively (p = 0.552). Postoperative toxicity events ≥ Grade III were 5 (41.7%) and 4 (44.4%), respectively (p = 0.623).ConclusionsIn our study we found a trend towards a higher complete pathological response-rate and disease-free survival in the intensification group compared to the standard group, with no differences in gastrointestinal toxicity. Well-designed randomized and controlled trials are needed to obtain conclusive data.

Безпосередні та віддалені результати першої лінії поліхіміотерапії у хворих на метастатичний тричі негативний рак грудної залози. Остаточний аналіз рандомізованого дослідження

The objective: was to evaluate the efficacy of the first line chemotherapy in patients with metastatic triple negative breast cancer (TNBC). Materials and methods. Open randomized study was performed including 122 patients with metastatic TNBC. The efficacy and safety of the first line chemotherapy of regimens АТ (n=59) – group 1, patients received doxorubicine 60 мг/м2 and paclitaxel 175 мг/м2 and ТР (n=63) – group 2, patients received paclitaxel 175 мг/м2 and carboplatin AUC 5 were evaluated. Results. The median duration of response was 9.5 months (4.5–13.25 months) in patients received AT regimen and 8.5 months (4.7–12.25 months), in TP regimen; no statistically significant differences were observed, р=0.836. The median progression free survival was 7 months (95% CI 5–26 months) in group 1 and 7.5 months (95% CI 6–35 months) in group 2, p=0.85. Both chemotherapy regimens (AT and TP) had mild or moderate toxicity profiles (grade 1 or 2 in most patients). No significant difference in gastrointestinal toxicity was observed. The incidence of grade 3–4 neutropenia was higher in patients of group 2 (TP regimen): 42.8% versus 27% (р&lt;0.05). Conclusions. Both regimens of chemotherapy (AT and TP) are appropriate to use in the first line setting in patients with metastatic TNBC. Key words: metastatic triple negative breast cancer, chemotherapy, progression free survival, chemotherapy toxicity.

Comparison of Treatment-Related Toxicity With Hypofractionated or Conventionally Fractionated Radiation Therapy for Prostate Cancer: A National Population-Based Study

AimsRandomised controlled trials have shown comparable early oncological outcomes after hypofractionated and conventionally fractionated radiotherapy in the radical treatment of prostate cancer (PCa). The effect of hypofractionation on treatment-related gastrointestinal and genitourinary toxicity remains uncertain, especially in older men and those with locally advanced PCa. Materials and methodsA population-based study of all patients treated with radical conventionally fractionated radiotherapy (n = 9106) and hypofractionated radiotherapy (n = 3027) in all radiotherapy centres in the English National Health Service between 2014 and 2016 was carried out. We identified severe gastrointestinal and genitourinary toxicity using a validated coding framework and compared conventionally fractionated and hypofractionated radiotherapy using a competing-risks proportional hazards regression analysis. ResultsThe median age in our cohort was 72 years old and most patients had locally advanced disease (65%). There was no difference in gastrointestinal toxicity (conventionally fractionated radiotherapy: 5.0 events/100 person-years; hypofractionated radiotherapy: 5.2 events/100 person-years; adjusted subdistribution hazard ratio: 1.00, 95% confidence interval: 0.89–1.13; P = 0.95) or genitourinary toxicity (conventionally fractionated radiotherapy: 2.3 events/100 person-years; hypofractionated radiotherapy: 2.3 events/100 person-years; adjusted subdistribution hazard ratio: 0.92, 95% confidence interval: 0.77–1.10; P = 0.35) between patients who received conventionally fractionated radiotherapy and those who received hypofractionated radiotherapy. ConclusionsThis national cohort study has shown that the use of hypofractionated radiotherapy in the radical treatment of PCa does not increase rates of severe gastrointestinal or genitourinary toxicity. Our findings also support the use of hypofractionated radiotherapy in older men and those with locally advanced PCa.

Role of Mediterranean diet in preventing platinum based gastrointestinal toxicity in gynecolocological malignancies: A single Institution experience.

BACKGROUNDGynecological malignancies represent a major cause of death in women and are often treated with platinum-based regimens. Patients undergoing chemotherapy suffer from alterations in nutritional status which may worsen gastrointestinal (GI) toxicities, quality of life and affect the overall prognosis. Indeed, assuring a good nutritional status and limiting toxicities during treatment are still major goals for clinicians.AIMTo assess the role of Mediterranean Diet (MD) in reducing GI toxicities in patients with gynecological cancers treated with platinum-based regimens.METHODSWe conducted an observational study on 22 patients with gynecological tumors treated with a platinum-based chemotherapy at Candiolo Cancer Institute FPO/IRCCS between January 2018 and June 2018. The food and frequency (FFQ) and the Patient-Reported Outcomes Common Terminology Criteria For Adverse Events (PRO-CTCAE) questionnaires were administered at baseline and at every Day 1 of each cycle. To evaluate the differences in GI toxicities the study population was divided in two groups according to the currently validated Mediterranean Diet Serving Score (MDSS) at baseline.RESULTSPatients with high MDSS reported a trend toward lower GI toxicities according to PRO-CTCAE at each timepoint (first evaluation: P = 0.7; second: P = 0.52; third: P = 0.01). In particular, difference in nausea frequency and gravity (P < 0.001), stomach pain frequency and gravity (P = 0.01 and P = 0.02), abdomen bloating frequency and gravity (P = 0.02 and P = 0.03), and interference with daily activities (P = 0.02) were highly statistically significant at the end of treatment. More than 60% of patients changed their food habits during chemotherapy mainly because of GI toxicities. A higher reduction of food intake, both in terms of caloric (P = 0.29) and of single nutrients emerged in the group experiencing higher toxicity.CONCLUSIONOur results show that adherence to MD possibly reduces GI toxicity and prevents nutritional status impairment during chemotherapy treatment. Bigger studies are needed to confirm our results.

Evaluation of High-Dose Melphalan Toxicity by Age in Patients Undergoing Autologous Stem Cell Transplant for Multiple Myeloma

Introduction Melphalan 200 mg/m2 on day -2 (Mel 200) is the standard conditioning regimen in autologous stem cell transplant (ASCT) for multiple myeloma (MM). This regimen is associated with significant gastrointestinal (GI) toxicity, including diarrhea, vomiting, and mucositis; therefore the dose may be reduced to 100-140 mg/m2 based on performance status or age. As the true difference in GI toxicity in older vs. younger patients is unknown, dose reductions may unnecessarily compromise efficacy outcomes. The objective of this study was to define the incidence of GI toxicity in patients age ≥ 60 vs. patients age Objectives Review dose adjustments for melphalan conditioning prior to ASCT in MM. Identify toxicities associated with melphalan conditioning for ASCT in MM. Compare melphalan toxicity between patients age ≥ 60 vs. patients age Methods A retrospective cohort study was conducted via medical record review of adult patients treated with Mel 200 followed by first ASCT for MM from September 2012 to September 2017. The primary endpoint was incidence of GI toxicity, defined by Common Terminology Criteria for Adverse Events (CTCAE) grade 2 or higher diarrhea or grade 3 or higher mucositis during transplant admission. Secondary endpoints included subdivided primary endpoints, complete response rates, and measurements of recovery. Subgroup analyses were performed for patients age ≥ 65, and patients with renal impairment. Results A total of 167 patients were included, with 116 patients in the age Conclusion This single-center, retrospective medical record review demonstrated that patients older than age 60, particularly those 60 to 65 years of age, may receive Mel 200 with no difference in the incidence of GI toxicity compared to younger patients. Further study in a larger population of patients age 65 or older is needed to establish conclusions in this patient population.

Pharmacometabolomic prediction of individual differences of gastrointestinal toxicity complicating myelosuppression in rats induced by irinotecan

Pharmacometabolomics has been already successfully used in toxicity prediction for one specific adverse effect. However in clinical practice, two or more different toxicities are always accompanied with each other, which puts forward new challenges for pharmacometabolomics. Gastrointestinal toxicity and myelosuppression are two major adverse effects induced by Irinotecan (CPT-11), and often show large individual differences. In the current study, a pharmacometabolomic study was performed to screen the exclusive biomarkers in predose serums which could predict late-onset diarrhea and myelosuppression of CPT-11 simultaneously. The severity and sensitivity differences in gastrointestinal toxicity and myelosuppression were judged by delayed-onset diarrhea symptoms, histopathology examination, relative cytokines and blood cell counts. Mass spectrometry-based non-targeted and targeted metabolomics were conducted in sequence to dissect metabolite signatures in predose serums. Eventually, two groups of metabolites were screened out as predictors for individual differences in late-onset diarrhea and myelosuppression using binary logistic regression, respectively. This result was compared with existing predictors and validated by another independent external validation set. Our study indicates the prediction of toxicity could be possible upon predose metabolic profile. Pharmacometabolomics can be a potentially useful tool for complicating toxicity prediction. Our findings also provide a new insight into CPT-11 precision medicine.

Treatment-related toxicity in men who received Intensity-modulated versus 3D-conformal radiotherapy after radical prostatectomy: A national population-based study

Background and purposeIn the post-prostatectomy setting the value of Intensity-modulated (IMRT) relative to 3D-conformal radiotherapy (3D-CRT) in reducing toxicity remains unclear. We compared genitourinary (GU) and gastrointestinal (GI) toxicity after post-prostatectomy IMRT or 3D-CRT. Materials and methodsA population-based study of all patients treated with post-prostatectomy 3D-CRT (n = 2422) and IMRT (n = 603) was conducted between January 1 2010 and December 31 2013 in the English National Health Service. We identified severe GI and GU toxicity using a validated coding-framework and compared IMRT and 3D-CRT using a competing-risks proportional hazards regression analysis. ResultsThere was no difference in GI toxicity between patients who received IMRT and 3D-CRT (3D-CRT: 5.8 events/100 person-years; IMRT: 5.5 events/100 person-years; adjusted HR: 0.85, 95%CI: 0.63–1.13; p = 0.26). The GU toxicity rate was lower with IMRT but this effect was not statistically significant (3D-CRT: 5.4 events/100 person-years; IMRT: 3.8 events/100 person-years; adjusted HR: 0.76, 95%CI: 0.55–1.03; p = 0.08). ConclusionsThe use of post-prostatectomy IMRT compared to 3D-CRT is not associated with a statistically significant reduction in rates of severe GU and GI toxicity, although there is some evidence that GU toxicity is lower with IMRT. We would caution against rapid transition to post-prostatectomy IMRT until further evidence is available supporting its superiority.

Feasibility of Vascular Matching for Image Guided Pancreatic Stereotactic Body Radiation Therapy

Implanted fiducial markers (IFM) and biliary stents are established as targets for image-guidance during high dose stereotactic body RT (SBRT) in the treatment of pancreatic adenocarcinoma (PDAC). IFM are often well tolerated, but may delay treatment. Furthermore, the potential for IFM/stent migration may cause insufficient target volume coverage and normal tissue toxicity. This study evaluated the use of vascular matching (VM), IFM and stent matching for image-guidance in delivery of SBRT for patients with PDAC. We hypothesize that there is no difference in shifts or efficacy between IFM, stents, and VM. Between April 2011- November 2015, 39 patients received SBRT for treatment of PDAC at our institution. Cone beam CT (CBCT) was performed for setup verification. We retrospectively analyzed 221 CBCT images for setup shifts based on either IFM, stent or celiac and SMA vasculature contoured using electronic patient information management system, version 2.60 (IMPAC Medical Systems, Inc. Sunnyvale, CA). Average shift magnitudes in each axis and average vector magnitudes were calculated. RTOG acute gastrointestinal (GI) radiation morbidity scoring criteria were used to assess toxicity. Statistical analyses were performed using JMP 12.1.0 (SAS Institute Inc., Cary, NC). Kaplan-Meier calculations as well as analysis of variance, likelihood ratio, and Wilcoxon tests were used to evaluate local control and survival and compare groups. Fifteen patients (38.5%) were treated with IFM, 9 (23%) with stents, and 15 (38.5%) with VM. Waiting times from initial consult to radiation treatment in the IFM, stent, and VM groups were 24 days (range 2-91 days), 14 days (range 9-56 days), and 19 days (range 5-39 days), respectively. The average magnitude for superior/inferior shifts was 0.45 ± 0.42 mm (IFM), 0.48 ± 0.46 mm (stent), and 0.37 ± 0.33 mm (VM) (P = 0.24), lateral shifts 0.42 ± 0.99 mm, 0.29 ± 0.35 mm, and 0.26 ± 0.22 (P = 0.26), and anterior/posterior shifts were 0.33 ± 0.40 mm, 0.34 ± 0.28 mm, and 0.37 ± 0.28 mm (P = 0.70). Vector magnitudes were 0.85 ± 1.04 mm, 0.74 ± 0.53 mm, and 0.67 ± 0.36 mm, respectively (P = 0.24). There were no documented complications from IFM or stent placement. There were no significant differences in GI toxicities between groups (P = 0.25), with a single instance of Grade 3 toxicity in the stent group. There were no significant differences in tumor resectability (P = 0.70), margin status (P = 0.43), local control (P = 0.31), or overall survival (P = 0.88). Vascular matching is a feasible, less invasive image-guidance technique that allows for reproducible and convenient SBRT delivery to PDAC and shorter treatment delays. There was no difference in positional shifts, toxicity, or outcomes for patients planned with IFM, stents, or VM. VM may be preferable over more invasive methods of target localization.

Whole brain radiation therapy plus temozolomide in the treatment of brain metastases from non small cell lung cancer: a meta-analysis

To explore the efficacy and safety of whole brain radiation therapy (WBRT) plus temozolomide (TMZ) versus WBRT alone in the treatment of brain metastases from non-small cell lung cancer (NSCLC) through a meta-analysis. All previously published and some unpublished studies were comprehensively searched from the databases of MEDLINE, EMBASE, Cochrane Library and CBM, etc. The meta-analysis included all randomized controlled trials (RCTs) to compare WBRT plus TMZ with WBRT alone in treatment of brain metastases from NSCLC. The primary meta-analysis was based upon objective remission (OR) and toxicity and the second overall survival (OS). Four RCTs identified by two reviewers were included. There was significant improvement for the WBRT + TMZ group in OR rate (RR = 1.55, P = 0.003); but without significant improvement in OS (P = 0.69). Meanwhile, WHO grade III/IV hematologic toxicity of myelosuppression increased in the WBRT + TMZ group (RR = 2.47, P = 0.008), but without significant difference in gastrointestinal toxicity (P = 0.14). For the treatment of brain metastases from NSCLC, the combined therapy of WBRT plus TMZ improves OR, but without significant improvement in OS. And the incidence of myelosuppression is elevated. Future large-scale, high-quality and prospective phase III RCTs are needed to confirm the clinical efficacy and safety of WBRT plus TMZ.

The influence of daily localization during treatment of prostate cancer on acute toxicity.

214 Background: Various localization techniques are used in clinical practice but little comparative effectivess data exists. The purpose of this investigation is to assess the impact of daily localization (L) of the prostate on toxicity during definitive treatment of prostate cancer with intensity modulated radiotherapy (IMRT). Methods: This study details an IRB approved retrospective review of three cohorts of patients treated for prostate cancer utilizing IMRT and different L technologies at four academic hospitals. Patients were treated with no technique (N), gold markers (G), or electromagnetic beacons [Calypso] (C) for daily L. Acute genitourinary (GU) and gastrointestinal (GI) toxicity was assessed according to RTOG toxicity criteria; toxicity rates between the groups were compared using the chi-square test. Ordered logit regression of all major demographic (age, race), disease (PSA, Gleason grade, and T-stage) and treatment (hormones, pelvic nodal treatment, total dose, and prior TURP) characteristics on GU and on GI toxicity were performed. Results: One hundred fifty four men who received definitive dose escalated IMRT (no brachytherapy or post-prostatectomy patients) for prostate cancer from 2006 to 2010 and were included (G: n=47; C: n=47; N: n=60). The cohorts were balanced except race (higher percentage of African Americans in the N group, due to hospital demographics) and higher grade and use of pelvic nodal treatment (which were more common in the G and C groups). Bladder V40 and V70 were higher in the N group (45.4%/24.3%) compared to C (27.9%/12.3%) and G (37.4%/18.4%) groups; however, rectal V40 and V70 were similar among all 3 groups. Toxicity results are shown in the Table; as shown the C and G groups had lower GU toxicity (p &lt;0.001) respectively compared to the N group; no significant differences in GI toxicity were seen among the 3 groups. Ordered logit regression showed only daily L (p=0.041) reached significance in lowering GU toxicity, and only pelvic RT use (p =0.008) reached significance in increasing GI toxicity. Conclusions: In patients treated with IMRT, daily L was associated with lower acute GU toxicity but not acute GI toxicity.

Image‐guided dose‐escalated intensity‐modulated radiation therapy for prostate cancer: treating to doses beyond 78 Gy

Study Type - Therapy (case series) Level of Evidence 4 What's known on the subject? and What does the study add? High doses of radiotherapy correspond to higher cure rates. Most radiation centers in the UK and Australia limit prescription doses to 74-78 Gy and do not use IGRT and IMRT for all patients. The combination of IGRT and IMRT can limit the rectum and bladder to low doses allowing doses above 78 Gy to be delivered, including pelvic lymph node treatment, with low side effects. This paper provides a detailed guide of planning technique and expected toxicity to enable implementation of similar dose escalated prostate programmes in other radiotherapy centres. To determine the short-term side-effects of dose-escalated image-guided intensity-modulated radiation therapy (IG-IMRT) for the definitive treatment of prostate cancer. Eligible patients were treated at doses >78 Gy and with definitive intent. Patients from a prospective database with International Prostate Symptom Score (IPSS) and Common Terminology Criteria for Adverse Events, version 3.0 (CTCAE) toxicity were recorded weekly during treatment and at follow-up. In all, 101 patients were included, with doses ranging from 78.3 to 84 Gy (median = 79.3). The median (range) age was 71 (46-83) years; 60% received concurrent androgen deprivation and 35% had pelvic lymph node treatment. The median (range) IPSS at baseline, on treatment and at first follow-up were 7 (0-35), 15 (1-34) and 6 (0-30), respectively. The percentages of patients with grade 2 or higher toxicity during treatment, at 3 months and at 2 years were, respectively, 6.9%, 1% and 2% for gastrointestinal symptoms and 39%, 6.9% and 3% for genitourinary symptoms. There was no significant difference in gastrointestinal toxicity during treatment (P= 0.860) or at 3 months (P= 0.334) between patients with and without lymph node treatment. Doses >78 Gy delivered using daily image guidance and IMRT are well tolerated, and by 3 months short-term side-effects have normalized for the majority of patients.

Toxicity associated with capecitabine plus oxaliplatin in colorectal cancer before and after an institutional policy of capecitabine dose reduction

Background:Capecitabine plus oxaliplatin (CAPOX) is an established treatment option in colorectal cancer, but can be associated with severe toxicities.Methods:Following reporting of severe diarrhoea and dehydration with capecitabine 2000 mg m–2 per day plus oxaliplatin every 3 weeks (CAPOX 2000) in 2006, we instituted a policy change to reduce capecitabine dose to 1700 mg m–2 per day (CAPOX 1700). We undertook a retrospective analysis comparing toxicities encountered before and after this dose change.Results:Of the 400 patients treated, no significant differences were seen between the CAPOX 2000 and CAPOX 1700 in grades 3 and 4 diarrhoea (21% vs 19% P=0.80), stomatitis (0% vs 1% P=0.50) or grades 2–4 hand foot syndrome (16% vs 11% P=0.18). Grades 3 and 4 neutropenia (9.5% vs 3.5% P=0.03) and all grades hyperbilirubinaemia (60% vs 40% P<0.0001) were significantly reduced with CAPOX 1700. Rates of hospitalisation due to toxicities were not different between two groups (13% vs 11% P=0.53).Conclusions:No clinically or statistically significant differences in gastrointestinal toxicities or hospitalisation rate were seen after reducing our routine capecitabine dose from CAPOX 2000 to CAPOX 1700.

Intensity-modulated radiotherapy for the treatment of prostate cancer: a systematic review and economic evaluation

Prostate cancer (PC) is the most common cancer in men in the UK. Radiotherapy (RT) is a recognised treatment for PC and high-dose conformal radiotherapy (CRT) is the recommended standard of care for localised or locally advanced tumours. Intensity-modulated radiotherapy (IMRT) allows better dose distributions in RT. This report evaluates the clinical effectiveness and cost-effectiveness of IMRT for the radical treatment of PC. The following databases were searched: MEDLINE (1950-present), EMBASE (1980-present), Cumulative Index to Nursing and Allied Health Literature (CINAHL) (1982-present), BIOSIS (1985-present), the Cochrane Database of Systematic Reviews (1991-present), the Cochrane Controlled Trials Register (1991-present), the Science Citation Index (1900-present) and the NHS Centre for Reviews and Dissemination databases (Database of Abstracts of Reviews of Effects, NHS Economic Evaluation Database, Health Technology Assessment) (1991-present). MEDLINE In-Process & Other Non-Indexed Citations was searched to identify any studies not yet indexed on MEDLINE. Current research was identified through searching the UK Clinical Research Network, National Research Register archive, the Current Controlled Trials register and the Medical Research Council Clinical Trials Register. In addition, abstracts of the American Society of Clinical Oncology, the American Society for Therapeutic Radiology and Oncology, and European Society for Therapeutic Radiology and Oncology conferences were browsed. A systematic literature review of the clinical effectiveness and cost-effectiveness of IMRT in PC was conducted. Comparators were three-dimensional conformal radiotherapy (3DCRT) or radical prostatectomy. Outcomes sought were overall survival, biochemical [prostate-specific antigen (PSA)] relapse-free survival, toxicity and health-related quality of life (HRQoL). Fifteen electronic bibliographic databases were searched in January 2009 and updated in May 2009, and the reference lists of relevant articles were checked. Studies only published in languages other than English were excluded. An economic model was developed to examine the cost-effectiveness of IMRT in comparison to 3DCRT. Four scenarios were modelled based on the studies which reported both PSA survival and late gastrointestinal (GI) toxicity. In two scenarios equal PSA survival was assumed for IMRT and 3DCRT, the other two having greater PSA survival for the IMRT cohort. As there was very limited data on clinical outcomes, the model estimates progression to clinical failure and PC death from the surrogate outcome of PSA failure. No randomised controlled trials (RCTs) of IMRT versus 3DCRT in PC were available, but 13 non-randomised studies comparing IMRT with 3DCRT were found, of which five were available only as abstracts. One abstract reported overall survival. Biochemical relapse-free survival was not affected by treatment group, except where there was a dose difference between groups, in which case higher dose IMRT was favoured over lower dose 3DCRT. Most studies reported an advantage for IMRT in GI toxicity, attributed to increased conformality of treatment compared with 3DCRT, particularly with regard to volume of rectum treated. There was some indication that genitourinary toxicity was worse for patients treated with dose escalated IMRT, although most studies did not find a significant treatment effect. HRQoL improved for both treatment groups following radiotherapy, with any group difference resolved by 6 months after treatment. No comparative studies of IMRT versus prostatectomy were identified. No comparative studies of IMRT in PC patients with bone metastasis were identified. The strength of the conclusions of this review are limited by the lack of RCTs, and any comparative studies for some patient groups. The comparative data of IMRT versus 3DCRT seem to support the theory that higher doses, up to 81 Gy, can improve biochemical survival for patients with localised PC, concurring with data on CRT. The data also suggest that toxicity can be reduced by increasing conformality of treatment, particularly with regard to GI toxicity, which can be more easily achieved with IMRT than 3DCRT. Whether differences in GI toxicity between IMRT and 3DCRT are sufficient for IMRT to be cost-effective is uncertain, depending on the difference in incidence of GI toxicity, its duration and the cost difference between IMRT and 3DCRT.

How to Improve the Design of Trials of Antifungal Prophylaxis among Neutropenic Adults with Acute Leukemia

The risk for invasive fungal infections in patients with acute leukemia is generally low (4%-8%), and the routine use of fungal prophylaxis is not warranted except in specific high-risk groups that should be identified among this population. In a prophylactic study with a new agent, fluconazole or itraconazole oral solution represent good choices for the comparator because they are proven better than placebo or oral nonabsorbable antifungal agents in reducing the risk of invasive fungal infections in patients with acute leukemia. Because prophylaxis is most valuable when the risk of infection is high, patients with well-understood risk factors (severe mucosal disruption caused by chemotherapy, impaired cell-mediated immunity caused by steroids or fludarabine, use of a central venous catheter, and colonization by Candida species) should be selected. The end points for antifungal prophylactic trials should focus on proven and probable invasive fungal infections. Superficial and mucosal fungal infections do not represent a primary end point for these studies. Poor compliance should be considered as an interruption of treatment due to side effects and should be included in the criteria for failure. Fungus-related mortality should be evaluated as a failure of prophylaxis, whereas overall mortality may be influenced by many other cofactors. Differences in gastrointestinal toxicity of antifungal agents may limit the use of double-blind designs in some situations.

Acute morbidity reduction using 3DCRT for prostate carcinoma: a randomized study

Purpose: To study the effects on gastrointestinal and urological acute morbidity, a randomized toxicity study, comparing conventional and three-dimensional conformal radiotherapy (3DCRT) for prostate carcinoma was performed. To reveal possible volume effects, related to the observed toxicity, dose–volume histograms (DVHs) were used.Methods and Materials: From June 1994 to March 1996, 266 patients with prostate carcinoma, stage T1-4N0M0 were enrolled in the study. All patients were treated to a dose of 66 Gy (ICRU), using the same planning procedure, treatment technique, linear accelerator, and portal imaging procedure. However, patients in the conventional treatment arm were treated with rectangular, open fields, whereas conformal radiotherapy was performed with conformally shaped fields using a multileaf collimator. All treatment plans were made with a 3D planning system. The planning target volume (PTV) was defined to be the gross target volume (GTV) + 15 mm. Acute toxicity was evaluated using the EORTC/RTOG morbidity scoring system.Results: Patient and tumor characteristics were equally distributed between both study groups. The maximum toxicity was 57% grade 1 and 26% grade 2 gastrointestinal toxicity; 47% grade 1, 17% grade 2, and 2% grade > 2 urological toxicity. Comparing both study arms, a reduction in gastrointestinal toxicity was observed (32% and 19% grade 2 toxicity for conformal and conventional radiotherapy, respectively; p = 0.02). Further analysis revealed a marked reduction in medication for anal symptoms: this accounts for a large part of the statistical difference in gastrointestinal toxicity (18% vs. 14% [p = ns] grade 2 rectum/sigmoid toxicity and 16% vs. 8% [p < 0.0001] grade 2 anal toxicity for conventional and conformal radiotherapy, respectively). A strong correlation between exposure of the anus and anal toxicity was found, which explained the difference in anal toxicity between both study arms. No difference in urological toxicity between both treatment arms was found, despite a relatively large difference in bladder DVHs.Conclusions: The reduction in gastrointestinal morbidity was mainly accounted for by reduced toxicity for anal symptoms using 3DCRT. The study did not show a statistically significant reduction in acute rectum/sigmoid and bladder toxicity.