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Title: Adjuvant Chemoradiation for Gastric Cancer Using Epirubicin, Cisplatin, and 5-Fluorouracil Before and After Three-Dimensional Conformal Radiotherapy With Concurrent Infusional 5-Fluorouracil: A Multicenter Study of the Trans-Tasman Radiation Oncology Group

Abstract

Purpose: The INT0116 study has established postoperative chemoradiotherapy as the standard of care for completely resected gastric adenocarcinoma. However, the optimal chemoradiation regimen remains to be defined. We conducted a prospective, multicenter study to evaluate an alternative chemoradiation regimen that combines more current systemic treatment with modern techniques of radiotherapy delivery. Methods and Materials: Patients with adenocarcinoma of the stomach who had undergone an R0 resection were eligible. Adjuvant therapy consisted of one cycle of epirubicin, cisplatin, and 5-FU (ECF), followed by radiotherapy with concurrent infusional 5-FU, and then two additional cycles of ECF. Radiotherapy was delivered using precisely defined, multiple-field, three-dimensional conformal techniques. Results: A total of 54 assessable patients were enrolled from 19 institutions. The proportion of patients commencing Cycles 1, 2, and 3 of ECF chemotherapy were 100%, 81%, and 67% respectively. In all, 94% of patients who received radiotherapy completed treatment as planned. Grade 3/4 neutropenia occurred in 66% of patients with 7.4% developing febrile neutropenia. Most neutropenic episodes (83%) occurred in the post-radiotherapy period during cycles 2 and 3 of ECF. Grade 3/4 gastrointestinal toxicity occurred in 28% of patients. In all, 35% of radiotherapy treatment plans contained protocol deviations that were satisfactorily amended beforemore » commencement of treatment. At median follow-up of 36 months, the 3-year overall survival rate was estimated at 61.6%. Conclusions: This adjuvant regimen using ECF before and after three-dimensional conformal chemoradiation is feasible and can be safely delivered in a cooperative group setting. A regimen similar to this is currently being compared with the INT0116 regimen in a National Cancer Institute-sponsored, randomized Phase III trial.« less

Authors:
 [1];  [2];  [3];  [4];  [5];  [6]; ;  [7];  [8];  [9]
  1. Division of Radiation Oncology, Peter MacCallum Cancer Centre, Melbourne, Victoria (Australia)
  2. Department of Radiation Oncology, Austin Health, Melbourne, Victoria (Australia)
  3. Department of Radiation Therapy Services, Peter MacCallum Cancer Centre, Melbourne, Victoria (Australia)
  4. Department of Radiation Oncology, Westmead Hospital, Sydney, New South Wales (Australia)
  5. Department of Radiation Oncology, Sir Charles Gairdner Hospital, Perth, Western Australia (Australia)
  6. Department of Radiation Oncology, Princess Alexandra Hospital, Brisbane, Queensland (Australia)
  7. Centre for Biostatistics and Clinical Trials, Peter MacCallum Cancer Centre, Melbourne, Victoria (Australia)
  8. Division of Surgical Oncology, Peter MacCallum Cancer Centre, Melbourne, Victoria (Australia)
  9. Division of Hematology and Medical Oncology, Peter MacCallum Cancer Centre, Melbourne, Victoria (Australia)
Publication Date:
OSTI Identifier:
21491635
Resource Type:
Journal Article
Resource Relation:
Journal Name: International Journal of Radiation Oncology, Biology and Physics; Journal Volume: 79; Journal Issue: 3; Other Information: DOI: 10.1016/j.ijrobp.2009.11.042; PII: S0360-3016(09)03613-X; Copyright (c) 2011 Elsevier Science B.V., Amsterdam, The Netherlands, All rights reserved.
Country of Publication:
United States
Language:
English
Subject:
62 RADIOLOGY AND NUCLEAR MEDICINE; ANTINEOPLASTIC DRUGS; CARCINOMAS; COMBINED THERAPY; STOMACH; URACILS; AZINES; BODY; DIGESTIVE SYSTEM; DISEASES; DRUGS; GASTROINTESTINAL TRACT; HETEROCYCLIC COMPOUNDS; HYDROXY COMPOUNDS; MEDICINE; NEOPLASMS; ORGANIC COMPOUNDS; ORGANIC NITROGEN COMPOUNDS; ORGANS; PYRIMIDINES; THERAPY

Citation Formats

Leong, Trevor, E-mail: trevor.leong@petermac.or, Joon, Daryl Lim, Willis, David, Jayamoham, Jayasingham, Spry, Nigel, Harvey, Jennifer, Di Iulio, Juliana, Milner, Alvin, Mann, G. Bruce, and Michael, Michael. Adjuvant Chemoradiation for Gastric Cancer Using Epirubicin, Cisplatin, and 5-Fluorouracil Before and After Three-Dimensional Conformal Radiotherapy With Concurrent Infusional 5-Fluorouracil: A Multicenter Study of the Trans-Tasman Radiation Oncology Group. United States: N. p., 2011. Web. doi:10.1016/j.ijrobp.2009.11.042.
Leong, Trevor, E-mail: trevor.leong@petermac.or, Joon, Daryl Lim, Willis, David, Jayamoham, Jayasingham, Spry, Nigel, Harvey, Jennifer, Di Iulio, Juliana, Milner, Alvin, Mann, G. Bruce, & Michael, Michael. Adjuvant Chemoradiation for Gastric Cancer Using Epirubicin, Cisplatin, and 5-Fluorouracil Before and After Three-Dimensional Conformal Radiotherapy With Concurrent Infusional 5-Fluorouracil: A Multicenter Study of the Trans-Tasman Radiation Oncology Group. United States. doi:10.1016/j.ijrobp.2009.11.042.
Leong, Trevor, E-mail: trevor.leong@petermac.or, Joon, Daryl Lim, Willis, David, Jayamoham, Jayasingham, Spry, Nigel, Harvey, Jennifer, Di Iulio, Juliana, Milner, Alvin, Mann, G. Bruce, and Michael, Michael. 2011. "Adjuvant Chemoradiation for Gastric Cancer Using Epirubicin, Cisplatin, and 5-Fluorouracil Before and After Three-Dimensional Conformal Radiotherapy With Concurrent Infusional 5-Fluorouracil: A Multicenter Study of the Trans-Tasman Radiation Oncology Group". United States. doi:10.1016/j.ijrobp.2009.11.042.
@article{osti_21491635,
title = {Adjuvant Chemoradiation for Gastric Cancer Using Epirubicin, Cisplatin, and 5-Fluorouracil Before and After Three-Dimensional Conformal Radiotherapy With Concurrent Infusional 5-Fluorouracil: A Multicenter Study of the Trans-Tasman Radiation Oncology Group},
author = {Leong, Trevor, E-mail: trevor.leong@petermac.or and Joon, Daryl Lim and Willis, David and Jayamoham, Jayasingham and Spry, Nigel and Harvey, Jennifer and Di Iulio, Juliana and Milner, Alvin and Mann, G. Bruce and Michael, Michael},
abstractNote = {Purpose: The INT0116 study has established postoperative chemoradiotherapy as the standard of care for completely resected gastric adenocarcinoma. However, the optimal chemoradiation regimen remains to be defined. We conducted a prospective, multicenter study to evaluate an alternative chemoradiation regimen that combines more current systemic treatment with modern techniques of radiotherapy delivery. Methods and Materials: Patients with adenocarcinoma of the stomach who had undergone an R0 resection were eligible. Adjuvant therapy consisted of one cycle of epirubicin, cisplatin, and 5-FU (ECF), followed by radiotherapy with concurrent infusional 5-FU, and then two additional cycles of ECF. Radiotherapy was delivered using precisely defined, multiple-field, three-dimensional conformal techniques. Results: A total of 54 assessable patients were enrolled from 19 institutions. The proportion of patients commencing Cycles 1, 2, and 3 of ECF chemotherapy were 100%, 81%, and 67% respectively. In all, 94% of patients who received radiotherapy completed treatment as planned. Grade 3/4 neutropenia occurred in 66% of patients with 7.4% developing febrile neutropenia. Most neutropenic episodes (83%) occurred in the post-radiotherapy period during cycles 2 and 3 of ECF. Grade 3/4 gastrointestinal toxicity occurred in 28% of patients. In all, 35% of radiotherapy treatment plans contained protocol deviations that were satisfactorily amended before commencement of treatment. At median follow-up of 36 months, the 3-year overall survival rate was estimated at 61.6%. Conclusions: This adjuvant regimen using ECF before and after three-dimensional conformal chemoradiation is feasible and can be safely delivered in a cooperative group setting. A regimen similar to this is currently being compared with the INT0116 regimen in a National Cancer Institute-sponsored, randomized Phase III trial.},
doi = {10.1016/j.ijrobp.2009.11.042},
journal = {International Journal of Radiation Oncology, Biology and Physics},
number = 3,
volume = 79,
place = {United States},
year = 2011,
month = 3
}
  • Purpose: To compare dosimetric endpoints between three-dimensional conformal radiotherapy (3D-CRT) and intensity-modulated radiotherapy (IMRT) at our center with limited IMRT experience, and to perform an external audit of the IMRT plans. Methods and Materials: Ten patients, who received adjuvant chemoradiation for gastric cancer, formed the study cohort. For standardization, the planning target volume (PTV) and organs at risk were recontoured with the assistance of a study protocol radiologic atlas. The cohort was replanned with CMS Xio to generate coplanar 3D-CRT and IMRT plans. All 10 datasets, including volumes but without the plans (i.e., blinded), were transmitted to an experienced centermore » where IMRT plans were designed using Nomos Corvus (IMRT-C) and ADAC Pinnacle (IMRT-P). All IMRT plans were normalized to D95% receiving 45 Gy. Results: Intensity-modulated radiotherapy yielded higher PTV V45 (volume that receives {>=}45 Gy) (p < 0.001) than 3D-CRT. No difference in V20 was seen in the right (p = 0.9) and left (p 0.3) kidneys, but the liver mean dose (p < 0.001) was superior with IMRT. For the external audit, IMRT-C (p = 0.002) and IMRT-P (p < 0.001) achieved significantly lower left kidney V20 than IMRT, and IMRT-P (p < 0.001) achieved lower right kidney V20 than IMRT. The IMRT-C (p = 0.003) but not IMRT-P (p = 0.6) had lower liver mean doses than IMRT. Conclusions: At our institution with early IMRT experience, IMRT improved PTV dose coverage and liver doses but not kidney doses. An external audit of IMRT plans showed that an experienced center can yield superior IMRT plans.« less
  • Purpose: To determine the maximum tolerated dose in concurrent three-dimensional conformal radiotherapy (3D-CRT) with chemotherapy for unresectable Stage III non-small-cell lung cancer (NSCLC). Patients and Methods: Eligible patients with unresectable Stage III NSCLC, age {>=}20 years, performance status 0-1, percent of volume of normal lung receiving 20 GY or more (V{sub 20}) {<=}30% received three to four cycles of cisplatin (80 mg/m{sup 2} Day 1) and vinorelbine (20 mg/m{sup 2} Days 1 and 8) repeated every 4 weeks. The doses of 3D-CRT were 66 Gy, 72 Gy, and 78 Gy at dose levels 1 to 3, respectively. Results: Of themore » 17, 16, and 24 patients assessed for eligibility, 13 (76%), 12 (75%), and 6 (25%) were enrolled at dose levels 1 to 3, respectively. The main reasons for exclusion were V{sub 20} >30% (n = 10) and overdose to the esophagus (n = 8) and brachial plexus (n = 2). There were 26 men and 5 women, with a median age of 60 years (range, 41-75). The full planned dose of radiotherapy could be administered to all the patients. Grade 3-4 neutropenia and febrile neutropenia were noted in 24 (77%) and 5 (16%) of the 31 patients, respectively. Grade 4 infection, Grade 3 esophagitis, and Grade 3 pulmonary toxicity were noted in 1 patient, 2 patients, and 1 patient, respectively. The dose-limiting toxicity was noted in 17% of the patients at each dose level. The median survival and 3-year and 4-year survival rates were 41.9 months, 72.3%, and 49.2%, respectively. Conclusions: 72 Gy was the maximum dose that could be achieved in most patients, given the predetermined normal tissue constraints.« less
  • Purpose: Partial breast irradiation (PBI) after lumpectomy may be an option for selected patients with early breast cancer. A feasibility study of accelerated PBI delivered using external beam 3-dimensional conformal radiation therapy (RT) was undertaken at 8 Australasian centers. The present study evaluated the impact of patient, tumor, and RT technique-related factors on the quality of RT plans as determined by the dose–volume parameters of organs at risk. Methods and Materials: Forty-eight patients were enrolled in the study. All RT plans were centrally reviewed using predefined dosimetric criteria before commencement and after completion of protocol therapy. The RT plans ofmore » 47 patients met the dose–volume constraints, and all 47 patients received PBI to a prescribed dose of 38.5 Gy in 10 fractions. The RT plan quality was determined by volumes of the ipsilateral whole breast, lung, and heart that received 50% and 95%; 30%; and 5% of the prescribed dose, respectively. Patient, tumor, and RT technique-related factors were investigated for association with the parameters of RT plan quality. Results: The ratio of the planning target volume to the ipsilateral whole-breast volume was significantly associated with the ipsilateral breast doses on multiple variable analyses. The distance of the postlumpectomy surgical cavity from the heart and lung were predictive for heart and lung doses, respectively. A distance between surgical cavity and heart of >4 cm typically resulted in <1% of the heart volume receiving 5 Gy or less. It was more difficult to meet the heart dose constraint for left-sided and medially located tumors. Conclusions: Partial breast irradiation using 3-dimensional conformal RT was feasible within the study constraints. The ratio of planning target volume to ipsilateral whole-breast volume and the distance of surgical cavity from the heart were significant predictors of the quality of treatment plan for external beam PBI.« less
  • Purpose: To assess, in a multicenter setting, the long-term outcomes of a brief course of high-dose methotrexate followed by radiotherapy for patients with primary central nervous system lymphoma (PCNSL). Methods and Materials: Forty-six patients were entered in a Phase II protocol consisting of methotrexate (1 g/m{sup 2} on Days 1 and 8), followed by whole-brain irradiation (45-50.4 Gy). The median follow-up time was 7 years, with a minimum follow-up of 5 years. Results: The 5-year survival estimate was 37% ({+-}14%, 95% confidence interval [CI]), with progression-free survival being 36% ({+-}15%, 95% CI), and median survival 36 months. Of the originalmore » 46 patients, 10 were alive, all without evidence of disease recurrence. A total of 11 patients have developed neurotoxicity, with the actuarial risk being 30% ({+-}18%, 95% CI) at 5 years but continuing to increase. For patients aged >60 years the risk of neurotoxicity at 7 years was 58% ({+-}30%, 95% CI). Conclusion: Combined-modality therapy, based on high-dose methotrexate, results in improved survival outcomes in PCNSL. The risk of neurotoxicity for patients aged >60 years is unacceptable with this regimen, although survival outcomes for patients aged >60 years were higher than in many other series.« less
  • Purpose: Liposomal drugs have a better tolerance profile and are highly accumulated in the tumor environment, properties that promise an optimal radiosensitization. We investigated the feasibility of the combination of 5-fluorouracil/lecovorin-based radio-chemotherapy with the administration of high weekly dose of a liposomal platinum formulation (Lipoplatin{sup TM}). Methods and Materials: Lipoplatin was given at a dose of 120mg/m{sup 2}/week, 5-fluorouracil at 400mg/m{sup 2}/week (Day 1), whereas radiotherapy was given through 3.5-Gy fractions on Days 2, 3, and 4. Two groups of 6 patients received four and five consecutive cycles, respectively. Results: Minimal nephrotoxicity (18.2% Grade 1) and neutropenia (9% Grade 3)more » was noted. Fatigue Grade 2 appeared in 25% of cases. Abdominal discomfort was reported by 18% of patients. No liver, kidney, gastric, or intestinal severe acute or late sequellae were documented, although the median follow-up of 9 months is certainly too low to allow safe conclusions. A net improvement in the performance status (from a median of 1 to 0) was recorded 2 months after the end of therapy. The response rates assessed with computed tomography, endoscopy, and biopsies confirmed 33% (2 of 6) tumor disappearance in patients treated with four cycles, which reached 80% (4 of 5) in patients receiving five cycles. Conclusions: Lipoplatin radio-chemotherapy is feasible, with minor hematological and nonhematological toxicity. The high complete response rates obtained support the testing of Lipoplatin in the adjuvant postoperative or preoperative radio-chemotherapy setting for the treatment of gastric cancer.« less