Trial Of Chemoradiation Research Articles

Phase II trial using combination of oxaliplatin, capecitabine, and celecoxib with concurrent radiation in patients with operable rectal cancer.

e14117 Background: Achieving complete pathological response (CPR) with neoadjuvant chemoradiation may predict a higher likelihood of long-term survival in patients with operable rectal cancer. However, studies done with single agent 5-FU based regimen have yielded conflicting data. This may be due to the inherent low activity of 5-FU in treating micrometastatic diseases. In animal models, celecoxib has been shown to increase cytotoxic effects of radiation while exerts protective effects to normal skin. We therefore conducted a phase II trial using combination of oxaliplatin, capecitabine and celecoxib concurrent with radiation in patients with operable rectal cancer. Methods: Twenty-one patients are enrolled in this single-arm phase II trial of neoadjuvant chemoradiation for patients with T3-4N0-2M0 rectal cancer from March 2006 to July 2009. Age range is 30-71 and eight are female. Pretreatment staging are assessed by colonoscopy, endoscopic ultrasound, and CT or PET/CT. Chemoradiation regimen consists of a total dose of 45 Gy radiation therapy in 25 fractions from Monday to Friday over 5 weeks. Oxaliplatin 50 mg/m2/weekly and capecitabine 850 mg/m2/bid are given five days a week with radiation therapy. Celebrex 200 mg bid are given throughout the duration of radiation without a break. Results: Seventeen out of twenty-one patients completed the treatment. Six patients (35.3%) had CPR, four (25.3%) had near complete pathological response (NCPR) and seven (41.1%) had residual disease (RD). The median survival has not been reached for the whole treatment group with a median follow-up of 24 (range 6-42) months. None of the patients with CPR had disease progression with follow-up range from 6-42 months. Grade 2-3 nausea, vomiting and diarrhea were the most common side effects. However, two patients had grade 4 symptoms that required hospitalization and subsequently developed fatal arrhythmia and sepsis. Conclusions: This regimen is effective in inducing a very high rate of CPR in patients with locally advanced resectable colon cancer. This phase II trial is ongoing and anticipate completion in 2010. No significant financial relationships to disclose.

A phase II trial of preoperative chemoradiation therapy plus bevacizumab and erlotinib in the treatment of localized esophageal cancer.

4108 Background: Neoadjuvant chemoradiation therapy is a standard treatment for localized esophageal cancers. The combination of carboplatin (C), paclitaxel (P), 5-FU and radiation therapy (RT) showed a path CR rate of 38% in a previous phase II study. Overexpression of VEGF and/or EGFR in esophageal cancers is associated with a poor prognosis. Both bevacizumab (B) and erlotinib (E) have antitumor activity in multiple solid tumors and are known radiosensitizers. This phase II study evaluated the combination of carboplatin, paclitaxel, 5-FU, bevacizumab, and erlotinib with RT as preoperative treatment of localized esophageal cancers. Methods: Eligibility included previously untreated stage I, II or III surgical candidates with histologically confirmed cancer of the esophagus or GE junction. The treatment regimen was: C: AUC 5 d 1, 22, P: 200 mg/m2 d 1, 22, 5-FU: 225 mg/m2/d IV C1 d 1-35, B: 15 mg/kg d 1, 22, and E: 100 mg PO d 1-42. RT was 1.8 Gy M-F to a total dose of 45 Gy. Patients were restaged between weeks 9-11 and had surgical resection between weeks 12-14. Results: 62 subjects enrolled, 59 currently available for analysis. Median age 64 (43-76), 54 M: 5F, ECOG PS 0 37 (63%). Adenocarcinoma 56 (95%), SCC 3 (5%). Pretreatment clinical stage: I 1 (2%), II 25 (42%), III 30 (51%). Common grade 3/4 toxicities: neutropenia (46%, 10% fever and neutropenia), mucositis (39%), diarrhea (27%), esophagitis (22%), rash (15%), and fatigue (15%). Other significant AEs: 1 G3 peripheral arterial thrombosis, 2 G4 wound complications. 3 treatment related deaths; 1 GI bleed and 2 post op deaths. 42 (71%) subjects have undergone surgical resection, with 3 still undergoing neo-adjuvant treatment. Path CR = 17 (30%); micro residual disease = 13 (23%); macro residual disease = 8 (14%). Conclusions: This multicenter phase II study of chemotherapy plus B and E with RT shows a path CR rate comparable to historical chemoradiation trials. Toxicity was not significantly increased compared to other neoadjuvant combination regimens for esophageal cancer. Given the potential difficulty to build upon this regimen with added agents, the further development of this regimen for patients with esophageal cancers is limited. Author Disclosure Employment or Leadership Position Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Genentech Genentech Genentech

Pancreatic cancer: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up

Pancreatic cancer: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up S. Cascinu, M. Falconi, V. Valentini & S. Jelic On behalf of the ESMO Guidelines Working Group* Department of Medical Oncology, Universita Politecnica delle Marche, Ancona; Department of Surgery and Gastroenterology, University of Verona, Verona; Department of Radiotherapy, Universita Cattolica del Sacro Cuore, Rome, Italy; Internal Medicine Service, Institute of Oncology and Radiology, Belgrade, Serbia

Serum CA 19-9 as a Marker of Resectability and Survival in Patients with Potentially Resectable Pancreatic Cancer Treated with Neoadjuvant Chemoradiation

PurposeThe role of carbohydrate antigen (CA) 19-9 in the evaluation of patients with resectable pancreatic cancer treated with neoadjuvant therapy prior to planned surgical resection is unknown. We evaluated CA 19-9 as a marker of therapeutic response, completion of therapy, and survival in patients enrolled on two recently reported clinical trials.Patients and MethodsWe analyzed patients with radiographically resectable adenocarcinoma of the head/uncinate process treated on two phase II trials of neoadjuvant chemoradiation. Patients without evidence of disease progression following chemoradiation underwent pancreaticoduodenectomy (PD). CA 19-9 was evaluated in patients with a normal bilirubin level.ResultsWe enrolled 174 patients, and 119 (68%) completed all therapy including PD. Pretreatment CA 19-9 <37 U/ml had a positive predictive value (PPV) for completing PD of 86% but a negative predictive value (NPV) of 33%. Among patients without evidence of disease at last follow-up, the highest pretreatment CA 19-9 was 1,125 U/ml. Restaging CA 19-9 <61 U/ml had a PPV of 93% and a NPV of 28% for completing PD among resectable patients. The area under the receiver-operating characteristics curve of pretreatment and restaging CA 19-9 levels for completing PD was 0.59 and 0.74, respectively. We identified no association between change in CA 19-9 and histopathologic response (P = 0.74).ConclusionsAlthough the PPV of CA 19-9 for completing neoadjuvant therapy and undergoing PD was high, its clinical utility was compromised by a low NPV. Decision-making for patients with resectable PC should remain based on clinical assessment and radiographic staging.

Induction Chemotherapy Followed by Chemoradiation in Locally Advanced Pancreatic Cancer: an Effective and Well-tolerated Treatment

Aims The treatment of locally advanced pancreatic cancer varies enormously both within the UK and internationally. Although chemoradiation is the treatment of choice in the USA, in the UK this modality is used infrequently because of concerns regarding both its efficacy and its toxicity. We reviewed our experience with induction chemotherapy and selective chemoradiation in an attempt to show that it is a well-tolerated treatment that may be superior to chemotherapy alone. Materials and methods Case notes of patients with locally advanced pancreatic cancer referred to the Velindre Cancer Centre between 1 March 2005 and 31 October 2007 were reviewed. Data on patient demographics, tumour characteristics, treatment and overall survival were collected retrospectively. Toxicity data during chemoradiation were collected prospectively. Patients who had non-progressive disease after 3 months of chemotherapy were planned for chemoradiation using three-dimensional conformal radiotherapy to a total dose of 4500–5040 cGy in 25–28 daily fractions with gemcitabine as a radiosensitiser. Results Of the 91 referrals, 69 (76%) were fit for active oncological treatment; 43/69 (62%) patients were considered for induction chemotherapy followed by chemoradiation and 16/43 (37%) patients received chemoradiation. The median overall survival for patients receiving primary chemotherapy ( n = 26) was 9.2 (6.8–11.9) months and was 15.3 (11.6–upper limit not reached) months for patients who received chemoradiation ( n = 16). During the induction chemotherapy 8/16 (50%) patients experienced grade 3/4 toxicity and there were five hospital admissions. During chemoradiation there were 6/16 (37.5%) cases of grade 3/4 toxicity and two hospital admissions. There were no treatment-related deaths. Overall, 94.5% of the intended radiotherapy dose and 84% of the concurrent chemotherapy dose was delivered. Conclusions In this UK network, about half of patients were considered for chemoradiation, but only 18% received it. Survival and treatment-related toxicity are consistent with data from other chemoradiation trials and in our series chemoradiation was tolerated better than chemotherapy alone. This supports the view that ‘consolidation’ chemoradiation is a viable treatment option that should be considered in selected patients with locally advanced non-metastatic pancreatic cancer.

Morphological Analysis of Pancreatic Adenocarcinoma on Multidetector Row Computed Tomography

Response Evaluation Criteria in Solid Tumors (RECIST) guidelines assume spherical shape of tumors. Morphology of pancreatic adenocarcinoma (PAC) on multidetector row computed tomography was investigated to evaluate the applicability of RECIST guidelines. Study population comprised 16 patients with histologically confirmed localized PAC enrolled in a phase II clinical trial of chemoradiation. Pancreatic adenocarcinomas were segmented on baseline and follow-up multidetector row computed tomography with commercially available software. Tumor volumes (mL), RECIST diameter (mm), volume equivalent sphere diameter (VESD, mm), maximum 3-dimensional diameter (M3DD, mm), and elongation value were obtained. RECIST diameter, VESD and M3DD of the tumors at baseline and follow-up were compared to determine differences. Elongation values were analyzed. The significance level was set at P less than 0.05. Mean volume, RECIST diameter, VESD, M3DD, and elongation for baseline versus follow-up studies were 23.12 mL versus 19.43 mL (P > 0.05), 41.86 mm versus 39.35 mm (P > 0.05), 33.14 mm versus 32.1 mm (P > 0.05), 51.76 mm versus 51.73 mm (P > 0.05), and 0.67 versus 0.76 (P > 0.05), respectively. There was a significant difference at baseline and follow-up between RECIST diameter, VESD, and M3DD (P < 0.05, in all instances). Our results suggest that PACs are not spherical in shape. Evaluation of PAC treatment response based on RECIST guidelines may not be accurate.

Toxicity and outcomes after chemoradiation for esophageal cancer in patients age 75 or older

Randomized trials of chemoradiation for esophageal cancer have included very few patients age > or = 75. In this retrospective study, we describe the outcomes and toxicity of full-dose chemoradiation in elderly patients with esophageal cancer. Patients, age > or = 75, treated with full-dose chemoradiation for esophageal carcinoma from 2002 to 2008 were retrospectively reviewed. Thirty-four patients were identified with a median age of 79.5 (range 75-89). The median Eastern Cooperative Oncology Group performance status was 1 (range 0-3) and the median Adult Comorbidity Evaluation-27 score was 1 (range 0-3). Twenty-eight patients received definitive and six received neoadjuvant chemoradiation. The median radiation dose delivered was 50.4 Gray (range 3.6-68.4 Gray). Platinum-based chemotherapy was used in 79.4% of patients. Fifty percent of the patients completed all planned radiation therapy (RT) and chemotherapy; 85.3% completed RT. Acute toxicity > or = grade 4 occurred in 38.2% of patients, and 70.6% of the patients required hospitalization, emergency department visit, and/or RT break. Median follow-up was 14.5 months among 7 survivors, and median survival was 12.0 months (95% confidence interval [CI]: 9.7 to 24.1 months). The actuarial overall survival at 2 years was 29.7% (95% CI: 16.6 to 52.6%). There were four treatment-related deaths. The median time to any recurrence was 10.4 months. Nineteen patients had a local and/or distant recurrence. In conclusion, elderly patients experienced substantial morbidity from chemoradiation, and long-term survival was low. Future efforts to improve treatment tolerability in the elderly are needed.

Research Highlights

Research Highlights

Weak expression of cyclooxygenase-2 is associated with poorer outcome in endemic nasopharyngeal carcinoma: analysis of data from randomized trial between radiation alone versus concurrent chemo-radiation (SQNP-01)

BackgroundOver-expression of cyclooxygenase-2 (COX-2) enzyme has been reported in nasopharyngeal carcinoma (NPC). However, the prognostic significance of this has yet to be conclusively determined. Thus, from our randomized trial of radiation versus concurrent chemoradiation in endemic NPC, we analyzed a cohort of tumour samples collected from participants from one referral hospital.Methods58 out of 88 patients from this institution had samples available for analysis. COX-2 expression levels were stratified by immunohistochemistry, into negligible, weak, moderate and strong, and correlated with overall and disease specific survivals.Results58% had negligible or weak COX-2 expression, while 14% and 28% had moderate and strong expression respectively. Weak COX-2 expression conferred a poorer median overall survival, 1.3 years for weak versus 6.3 years for negligible, 7.8 years, strong and not reached for moderate. There was a similar trend for disease specific survival.ConclusionContrary to literature published on other malignancies, our findings seemed to indicate that over-expression of COX-2 confer a better prognosis in patients with endemic NPC. Larger studies are required to conclusively determine the significance of COX-2 expression in these patients.

A randomized trial of chemoradiation using mitomycin or cisplatin, with or without maintenance cisplatin/5FU in squamous cell carcinoma of the anus (ACT II)

LBA4009 Background: Chemoradiotherapy (CRT) with 5-fluorouracil (5-FU) and mitomycin-C (MMC) is standard treatment for anal cancer. This trial addresses two questions: whether (i) replacing MMC with cisplatin (CDDP) improves the complete response (CR) rate, and (ii) two cycles of maintenance chemotherapy after CRT reduces recurrence. Methods: Between 2001 and 2008, 940 patients (pts) were recruited to a multicenter, randomized factorial trial. Pts received 5-FU (1,000mg/m2/day on d1–4 and 29–32), radiotherapy (RT) (50.4Gy in 28 fractions), and either MMC (12mg/m2, d1; n=471) or CDDP (60mg/m2 on d1 and 29; n=469). Pts were also randomized to receive maintenance therapy (n=448) 4 weeks after CRT (two cycles of CDDP and 5-FU weeks 11 and 14) or no maintenance (n=446). Maintenance randomization was not considered appropriate in 46 pts. Statistical power was ≥80% to detect a difference in the CR rate of 5% (CDDP vs MMC), and 30% reduction in recurrence (maintenance vs no maintenance). Results: Median age 58 yrs; 62% male, 38% female; tumor site - canal (81%), margin (15%); stage T1-T2 (50%), T3-T4 (43%); node negative (62%), positive (30%). Median follow-up was 3 yrs. The CR rate was 94% MMC and 95% CDDP (p=0.53). MMC pts had more acute grade 3/4 haematological toxicities (25 vs 13%, p<0.001) but this did not result in an increase in neutropaenic sepsis (3.1 vs 3.2%, p=0.93). Non-haematologic grade 3/4 toxicities were similar (61 vs 65%, p=0.22). Preliminary analysis shows no statistically significant difference in recurrence free survival (RFS) (HR 0.89, 95% CI 0.68, 1.18; p=0.42) or overall survival (HR 0.79, 95% CI 0.56,1.12; p=0.19) for the maintenance comparison. The number of pre-treatment colostomies not reversed were similar between treatments (18 MMC vs 14 CDDP, p=0.65, Maint/No maint, p=0.23) and only 9 disease-free pts had colostomies performed (5 MMC, 4 CDDP). Conclusions: ACT II is the largest trial conducted in anal cancer. High CR (95%) and RFS (75% at 3 yrs) rates were achieved with this CRT. This excellent outcome may have been influenced by the absence of a gap in the RT schedule. There was no difference in CR rates between MMC and CDDP or in RFS rates with or without maintenance chemotherapy. 5-FU, MMC with RT remains the standard of care. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Merck-Serono, Pfizer, Roche, sanofi-aventis Merck Serono, Roche, sanofi- aventis AstraZeneca, Merck Serono, Pfizer, Roche

A randomized trial of chemoradiation using mitomycin or cisplatin, with or without maintenance cisplatin/5FU in squamous cell carcinoma of the anus (ACT II)

LBA4009 Background: Chemoradiotherapy (CRT) with 5-fluorouracil (5-FU) and mitomycin-C (MMC) is standard treatment for anal cancer. This trial addresses two questions: whether (i) replacing MMC with cisplatin (CDDP) improves the complete response (CR) rate, and (ii) two cycles of maintenance chemotherapy after CRT reduces recurrence. Methods: Between 2001 and 2008, 940 patients (pts) were recruited to a multicenter, randomized factorial trial. Pts received 5-FU (1,000mg/m2/day on d1–4 and 29–32), radiotherapy (RT) (50.4Gy in 28 fractions), and either MMC (12mg/m2, d1; n=471) or CDDP (60mg/m2 on d1 and 29; n=469). Pts were also randomized to receive maintenance therapy (n=448) 4 weeks after CRT (two cycles of CDDP and 5-FU weeks 11 and 14) or no maintenance (n=446). Maintenance randomization was not considered appropriate in 46 pts. Statistical power was ≥80% to detect a difference in the CR rate of 5% (CDDP vs MMC), and 30% reduction in recurrence (maintenance vs no maintenance). Results: Median age 58 yrs; 62% male, 38% female; tumor site - canal (81%), margin (15%); stage T1-T2 (50%), T3-T4 (43%); node negative (62%), positive (30%). Median follow-up was 3 yrs. The CR rate was 94% MMC and 95% CDDP (p=0.53). MMC pts had more acute grade 3/4 haematological toxicities (25 vs 13%, p&lt;0.001) but this did not result in an increase in neutropaenic sepsis (3.1 vs 3.2%, p=0.93). Non-haematologic grade 3/4 toxicities were similar (61 vs 65%, p=0.22). Preliminary analysis shows no statistically significant difference in recurrence free survival (RFS) (HR 0.89, 95% CI 0.68, 1.18; p=0.42) or overall survival (HR 0.79, 95% CI 0.56,1.12; p=0.19) for the maintenance comparison. The number of pre-treatment colostomies not reversed were similar between treatments (18 MMC vs 14 CDDP, p=0.65, Maint/No maint, p=0.23) and only 9 disease-free pts had colostomies performed (5 MMC, 4 CDDP). Conclusions: ACT II is the largest trial conducted in anal cancer. High CR (95%) and RFS (75% at 3 yrs) rates were achieved with this CRT. This excellent outcome may have been influenced by the absence of a gap in the RT schedule. There was no difference in CR rates between MMC and CDDP or in RFS rates with or without maintenance chemotherapy. 5-FU, MMC with RT remains the standard of care. [Table: see text]

Association of tobacco (T) use with risk of distant metastases (DM), tumor recurrence, and death in patients (pts) with HPV-positive (+) squamous cell cancer of the oropharynx (SCCOP)

6001 Background: Chemoradiation (CRT) for HPV (+) SCCOP is associated with a more favorable prognosis than HPV-negative (-) SCCOP. However, the interaction of HPV and T in terms of etiology and disease progression remains unclear. HPV (+) SCCOP pts were prospectively studied to determine if T use was a key variable in discriminating which pts would develop DM, locoregional recurrences (LR), or second primaries (SP). Methods: From 1999–2007, 124 pts with stage III/IV SCCOP were enrolled in one of two CRT trials. Tumor specimens were analyzed for HPV presence and type. Use of T, determined via self-reporting and chart review, was recorded as both continuous (number of pack-yrs) and categorical (never, former, and current) variables. Former T users were subdivided into an early cessation group (quit ≥ 20 yrs prior to diagnosis) and a late cessation group (quit &lt; 20 yrs prior to diagnosis). T use and HPV status were analyzed with respect to survival &amp; the development of DM, LR, or SP. Results: Of the 124 pts, 100 (81%) were HPV (+), 22 of which developed disease progression (22%). Twenty-four were HPV (-), 12 of which had disease progression (50%). Seventeen of 124 pts (14%) developed DM [12 HPV (+), 5 HPV (-)]. Nine of 124 (7%) developed LR [5 HPV (+), 4 HPV (-)], and 8 of 124 (7%) developed SP [5 HPV (+), 3 HPV (-)]. Thirty-two HPV (+) pts were never-T users, 88% (28/32) of which remain alive with no evidence of disease; 3 died from other causes and 1 died of lung metastases from SCCOP. Sixty-eight were HPV (+) and had T exposure. Of 46 former T users, 37/46 (80%) are living. Twenty were HPV (+) and in the early cessation group, 35% (7/20) of which had disease progression [3 LR, 3 DM, 1 SP]. Twenty-six HPV (+) pts were former T users in the late cessation group, 11% (3/26) of which had disease progression [2 DM, 1 SP]. Of 22 HPV (+) current T users, 68% (15/22) are alive and 36% (8/22) have developed disease progression. Seventeen of the 24 HPV (-) pts were current T users, 47% (8/17) of which developed disease progression. Conclusions: Never-T users with HPV-positive SCCOP have improved survival &amp; reduced risk of disease progression compared to HPV (+) &amp; HPV (-) former &amp; current T users. No significant financial relationships to disclose.

A randomized trial of chemoradiation using mitomycin or cisplatin, with or without maintenance cisplatin/5FU in squamous cell carcinoma of the anus (ACT II)

LBA4009 The full, final text of this abstract will be available in Part II of the 2009 ASCO Annual Meeting Proceedings, distributed onsite at the Meeting on May 30, 2009, and as a supplement to the June 20, 2009, issue of the Journal of Clinical Oncology. [Table: see text]

Aprepitant/5HT-3 antagonist (EMEND) for the prevention of chemoradiation-induced nausea and vomiting (CRINV) in patients receiving gemcitabine/ 5-FU–based chemoradiation and concurrent upper abdominal radiation for pancreatic cancer

e20661 Background: Significant chemoradiation-induced nausea and vomiting (CRINV) occurs in patients (pts) receiving chemoradiation for pancreatic cancer. The aim of this trial was to determine if prophylactic Aprepitant/5HT-3/dexamethasone added to standard chemoradiation resulted in less CRINV when compared to historical controls. Methods: Pts with locally advanced or resected pancreatic cancer received wkly Gemcitabine (200 mg/m2) and continuous infusion 5-fluorouracil (5-FU) or oral capecitabine with concurrent radiation (50.4 Gy). Aprepitant (125 mg p.o.) was given each Monday (day 1) of each week 1 hr before the gemcitabine infusion and on days 2 and 3 (80 mg p.o.) - 1 hour prior to the radiation. A 5HT-3 antagonist was given orally 30–60 minutes prior to the chemotherapy and dexamethasone (12 mg) was given on day 1 and repeated at a dose of 8 mg on days 2 and 3 with the aprepitant. Grade III/IV nausea was assessed using NCI CTC v. 3.0. The Multinational Association of Supportive Care in Cancer Antiemesis Tool (MAT) questionnaire was completed at baseline prior to the start of all therapy, Time 1 (T#1), repeated at the end of the first week (T#2) and then repeated again at the end of the last full week of chemoradiation (T#3). Results: Of the 17 patients available for analysis, CTC grade III nausea and grade IV vomiting was observed in one patient (6%) during the entire treatment course. Utilizing the MAT at T#1, T#2 and T#3 respectively; 3/15, 4/15 and 2/13 pts reported experiencing any level of nausea. At those same time points; 0/15, 1/15 and 0/13 pts reported vomiting. The range of the average degree of nausea reported on a scale from 1–10 (worst) was 2.5 -3.67 over the study period. During treatment, 54–64% of participants reported no nausea/vomiting (N/V). For those patients who experienced N/V, it was rated as mild to moderate with only 3 of 17 requiring additional anti-emetics. Conclusions: Prophylactic Aprepitant/5HT-3/dexamethasone therapy resulted in minimal CRINV for pts receiving upper abdominal chemoradiation in this feasibility study. This regimen may be soon be integrated in to future CALGB pancreatic chemoradiation trials. [Table: see text]

Increased risk of high‐grade dermatologic toxicities with radiation plus epidermal growth factor receptor inhibitor therapy

The addition of epidermal growth factor receptor (EGFR) inhibitors to radiotherapy has produced increased locoregional control and has reduced mortality from various solid tumors with few additional toxicities. Although anecdotal reports have suggested increased radiation dermatitis, the overall effect of these regimens on dermatologic toxicities has not been ascertained. Dermatologic toxicity data were analyzed from abstracts presented at the annual meetings of the American Society of Clinical Oncology, the American Society of Therapeutic Radiology and Oncology, Cochrane Collaboration, MEDLINE, and EMBASE databases. Phase 1, 2, and 3 trials that reported on radiation dermatitis, rash, and mucositis were included. Collaborative group, phase 3, randomized radiotherapy and chemoradiation trials served as controls. The summary incidence rate and relative risk were calculated using a random-effects or fixed-effects model, depending on the heterogeneity of included studies. The summary incidence of high-grade radiation dermatitis in patients who received radiation plus EGFR inhibitors was 31.3% (95% confidence interval [95% CI], 17.7%-49.1%), rash in 16.1% (95% CI, 12.8%-20.1%), and mucositis occurred in 52.7% (95% CI, 38.1%-66.9%). When the combination of radiotherapy plus EGFR inhibitors was compared with radiation alone, the risk ratio for radiation dermatitis was 2.38 (95% CI, 1.8-3.2; P<.001), rash was 3.01 (95% CI, 2.0-4.6; P<.001), for mucositis it was 1.76 (95% CI, 1.5-2.0; P<.001), suggesting that there was an increased risk of dermatologic toxicities with the combined regimen. EGFR inhibitors combined with radiation were associated with a significant increase in the risk for high-grade radiation dermatitis, rash, and mucositis. Although increased rash is expected with EGFR inhibitors, in-field dermatitis and mucositis represent new safety concerns. Improved reporting and management strategies are critical for quality of life and the optimization of radiation plus EGFR inhibitor protocols.

KGOG's &amp; KSGOC's Symposium, Nov. 12-13, 2009

KGOG's &amp; KSGOC's Symposium, Nov. 12-13, 2009

Accrediting radiation technique in a multicentre trial of chemoradiation for pancreatic cancer

Before a multicentre trial of 3-D conformal radiotherapy to treat cancer of the pancreas, participating clinicians were asked to complete an accreditation exercise. This involved planning two test cases according to the study protocol, then returning hard copies of the plans and dosimetric data for review. Any radiation technique that achieved the specified constraints was allowed. Eighteen treatment plans were assessed. Seven plans were prescribed incorrect doses and two of the planning target volumes did not comply with protocol guidelines. All plans met predefined normal tissue dose constraints. The identified errors were attributable to unforeseen ambiguities in protocol documentation. They were addressed by feedback and corresponding amendments to protocol documentation. Summary radiobiological measures including total weighted normal tissue equivalent uniform dose varied significantly between centres. This accreditation exercise successfully identified significant potential sources of protocol violations, which were then easily corrected. We believe that this process should be applied to all clinical trials involving radiotherapy. Due to the limitations of data analysis with hard-copy information only, it is recommended that complete planning datasets from treatment-planning systems be collected through a digital submission process.

Neoadjuvant Chemoradiation for Rectal Cancer

Significant advances have been made in the treatment of rectal cancer patients. Phase III studies have demonstrated the efficacy of neoadjuvant and adjuvant radiation therapy and chemotherapy in improving the outcome of patients with locally advanced disease. Data from the randomized German CAO/ARO/AIO-94 trial of preoperative versus postoperative chemoradiation has established the foundation for the use of preoperative chemoradiation in the treatment of patients with clinical stage II and III rectal cancer. Phase III studies are now examining innovative strategies of chemotherapy and targeted agents with radiation therapy.

Four consecutive multicenter phase II trials of adjuvant chemoradiation in patients with completely resected high-risk gastric cancer: the experience of the German AIO/ARO/CAO group

Feasibility and efficacy of four different adjuvant radiochemotherapy regimens in patients with completely resected gastric cancer were evaluated in consecutive cooperative phase II trials using different 5-fluorouracil (5-FU)-based combination chemotherapies (CTX) and 5-FU-enhanced radiotherapy. Between 2000 and 2005, 157 patients with completely resected gastric adenocarcinoma were included. The study design was based on two cycles of CTX and irradiation with 45 Gy plus concomitant 5-FU 225 mg/m(2) per 24 h between these two cycles. CTX cycles consisted of 5-FU, folinic acid (FA), cisplatin plus paclitaxel (FLPP); 5-FU, FA and cisplatin (FLP); 5-FU, FA and irinotecan (FLI); or 5-FU, cisplatin plus docetaxel (FPD). Median follow-up for all four trials was 18 months (range, 1-64) without significant difference between the four regimens: FLPP 30 months (2-46+), FLP 18 months (1-64+), FLI 15 months (1-26), FPD 10 months (5-19+). Treatment associated toxicity was tolerable and did not differ significantly between the four CTX regimens. Across all patients grade (3/4), toxicities during the first cycle/chemoradiation/second cycle consisted of leukocytopenia 4%/2%/30%, anorexia 5%/10%/6%, diarrhea 6%/1%/3%, nausea 2%/7%/2%. Early death occurred in one patient due to Pneumocystis carinii pneumonia. Median progression free survival was 23 months for FLPP, 18 months for FLP, 14 months for FLI, 9 months for FPD (not significant). One-year-overall survival rates were 95% for FLPP, 82% for FLP, 94% for FLI, 86% for FPD. Adjuvant radiochemotherapy in patients with gastric cancer can be safely given continuous infusion of 5-FU at 225 mg/m(2) per day. In addition, a variety of 5-FU-based multiagent chemotherapy regimen with defined activity in gastric cancer appears both safe and effective when given prior and after radiochemotherapy in this setting.

Maximum Tolerated Dose - Results of Phase I Trial of Weekly Paclitaxel and Cisplatin with Radiation Therapy in Carcinoma Cervix

Maximum Tolerated Dose - Results of Phase I Trial of Weekly Paclitaxel and Cisplatin with Radiation Therapy in Carcinoma Cervix