Toxicity and efficacy of concurrent gemcitabine and radiotherapy for locally advanced pancreatic cancer
Rent the article at a discountRent now
* Final gross prices may vary according to local VAT.Get Access
Background. Gemcitabine and radiotherapy are a potent combination. A clinical assessment of the therapeutic ratio for locally advanced pancreatic cancer patients has not yet been reported.
Aim of Study. To assess the toxicity, survival, and pattern of failure of locally advanced pancreatic cancer patients treated with concurrent gemcitabine-based chemoradiation.
Patients and Methods. Between the dates of December 1996 and August 2000 51 patients with locally advanced unresectable adenocarcinoma of the pancreas were treated with concurrent gemcitabine and radiotherapy at MDACC. Patients received 250–500 mg/m2 of gemcitabine weekly ×7 over 30 min and 30–33 Gy in 10–11 fractions over two weeks to the primary tumor and regional lymphatics. Severe toxicity was defined as admission >5 d, mucosal ulceration, >3 dose deletions of gemcitabine or toxicity resulting in surgical intervention or that resulted in death.
Results. The median survival was 11 mo. Overall, 37 of 51 patients had objective evidence of local progression. The actuarial rate of local progression rate at 9 mo was 70%. The 9-mo distant metastasis rate was 52%. Tumors ≥ 10 cm2 had worse local control, distant control, and overall survival. Six patients underwent pancreaticoduodenectomy after therapy. After review of the imaging, only four of these patients had minimal arterial involvement, one was incorrectly staged, and one had initial inflammatory change on CT that resolved. Twelve of 51 (24%) patients suffered severe acute toxicity, and 17 of 51 (33%) patients were admitted for supportive care.
Conclusion. Concurrent gemcitabine and radiotherapy can be a very difficult combination to administer safely. Our results do not suggest a prolongation of median survival for patients with localized pancreatic cancer treated with this therapy. It is possible that gemcitabine-based chemoradiation contributes to the margin-negative resectability of a small number of patients with minimal arterial involvement, but this benefit is obscured by the frequent toxicity encountered in most patients. Locally advanced pancreatic cancer patients should continue to be enrolled on prospective studies investigating novel combinations of cytotoxic and/or biologic agents with concurrent radiotherapy.
Milas L., Fuji T, Hunter N. Enhancement of tumor radioresponse in vivo by gemcitabine. Cancer Res 1999;59: 107–114.PubMed
Mason KA, Milas L, Hunter NR, et al. Maximizing therapeutic gain with gencitabine and franctionated radiation. Int J Radiat Oncol, Biol, Phys 1999; 44(5): 1125–1135.
Joschko M, Webster L, Groves J, et al. Radioenhancement by gemcitabine with accelerated fractionated radiotherapy in a human tumor xenograft model. Radiat Oncol Invest 1997; 5: 62–71.CrossRef
Lawrence T, Eisbruch A, Shewach D. Gemcitabine-mediated radiosensitization. Semin Oncol 1997; 24(2, S7): S724-S728.
Lawrence TS, Chang EY, Hertel L, Shewach D. Gemcitabine radiosensitizes human pancreas cancer cells. Proc AACR 1994; 35: A3855.
McGinn C, Shureiqi J, Robertson J, et al. A phase I trial of radiation dose escalation with full dose gemcitabine in patients with pancreatic cancer. Proc of ASCO 1999; 18: 274a.
Wolff R, Evans D, Lenzi R, et al. Phase I trial of gemcitabine combined with radiation for the treatment of locally advanced pancreatic adenocarcinoma. Clin Cancer Invest 1999; in press.
Abbruzzese JL, Grunewald R, Weeks EA, et al. A phase I clinical, plasma, and cellular pharmacology study of gemcitabine. J Clin Oncol 1991; 9(3): 491–498.PubMed
Burris HA, 3rd, Moore MJ, Andersen J, et al. Improvements in survival and clinical benefit with gemcitabine as first-line therapy for patients with advanced pancreas cancer: a randomized trial [see comments]. J Clin Oncol 1997; 15(6): 2403–2413.PubMed
Rothenberg ML, Burris HA, III, Anderson JS, et al. Gemcitabine: Effective palliative therapy for pancreas cancer patients failing 5-FU. Proc of ASCO 1995; 14: 198.
Anonymous. A multi-institutional comparative trial of radiation therapy alone and in combination with 5-fluorouracil for locally unresectable pancreatic carcinoma. The Gastrointestinal Tumor Study Group. Ann Surg 1979; 189(2): 205–208.
Moertel CG, Frytak S, Hahn RG, et al. Therapy of locally unresectable pancreatic carcinoma: a randomized comparison of high dose (6000 rads) radiation alone, moderate dose radiation (4000 rads + 5-fluorouracil), and high dose radiation + 5-fluorouracil: The Gastrointestinal Tumor Study Group. Cancer 1981; 48(8): 1705–1710.PubMedCrossRef
Anonymous. Radiation therapy combined with Adriamycin or 5-fluorouracil for the treatment of locally resectable pancreatic carcinoma. Gastrointestinal Tumor Study Group. Cancer 1985; 56(11): 2563–2568.
Anonymous. Treatment of locally unresectable carcinoma of the pancreas: comparison of combined-modality therapy (chemotherapy plus radiotherapy) to chemotherapy alone. Gastrointestinal Tumor Study Group. J Natl Cancer Instit 1988; 80(10): 751–755.
Mohiuddin M, Cantor RJ, Biermann W, Weiss SM, Barbot D, Rosato FE. Combined modality treatment of localized unresectable adehocarcinoma of the pancreas. In J Radiat Oncol, Biol, Phys 1988; 14(1): 79–84.
Milas L, Fujii T, Hunter N, et al. Enhancement of tumor radioresponse in vivo by gemcitabine. Cancer Res 1999; 59(1): 107–114.PubMed
Hittelman W, Fujii T, Hunter N, et al. Identification of a window of therapeutic opportunity for the combination of gemcitabine and radiation. Proc Annu Meet Am Assoc Cancer Res 1996; 37:A1973.
Tempero M, Plunkett W, Ruiz V, et al. Randomized phase II trial of dose intense gemcitabine by standard infusion vs. fixed dose rate in metastatic pancreatic adenocarcinoma. Proceedings of ASCO 1999; 18: Abst. #1048.
McGinn CJ, Shureiqi I, Eckhauser FI, Colletti L, Smith DC, Brown D, TS L. Surgical resection following concurrent gemcitabine/radiation therapy in patients with previously unresectable pancreatic cancer. Radiother and Oncol 2000; 56: S57.
Epelbaum R, Rosenblatt E, Nasrallah S, et al. Phase II study of gemcitabine combined with radiation therapy in localized, unresectable pancreatic cancer. Proc of ASCO 2000; 19: abst #1029.
Brunner T, Grabenbauer G, Kasti S, Hohenberger W, Saurer R. A phase I trial of simultaneous gemcitabine/cisplatin and radiotherapy for patients with locally advanced pancreatic cancer. Proc ASCO 2000; 19: Abst. 1109.
Wilkowski R, Heinemann V, Rau H. Radiochemotherapy including gemcitabine and F-fluorouracil for treatment of locally advanced pancreatic cancer. ASCO 2000; 19: Abst. #1078.
Gunderson LL, Martin JK, Kvols LK, et al. Intraoperative and external beam irradiation +/-5-FU for locally advanced pancreatic cancer. Internat J Radiat Oncol, Biol, Phys 1987; 13(3): 319–329.
Mohiuddin M, Regine WF, Stevens J, et al. Combined intraoperative radiation and perioperative chemotherapy for unresectable cancers of the pancreas. J Clin Oncol 1995; 13(11): 2764–2768.PubMed
Garton GR, Gunderson LL, Nagorney DM, Donohue JH, Martin JK, McIlrath DC, Cha SS. High-dose preoperative external beam and intraoperative irradiation for locally advanced pancreatic cancer. Internat J Radiat Oncol, Biol, Phys 1993; 27(5): 1153–1157.CrossRef
Mohiuddin M, Rosato F, Barbot D, Schuricht A, Biermann W, Cantor R. Long-term results of combined modality — treatment with I-125 implantation for carcinoma of the pancreas. Internat J Radiat Oncol, Biol, Phys 1992; 23(2): 305–311.CrossRef
Breslin TA, Hess KR, Harbison DB, et al. Neoadjuvant chemoradiation for adenocarcinoma of the pancreas: treatment variables and survival duration. Ann Surg Oncol 2000; (In press).
Blackstock A, Bernard S, Richards F, et al. Phase I trial of twice-weekly gemcitabine and concurrent radiation in patients with advanced pancreatic cancer. J Clin Oncol 1999; 17(7): 2208–2212.PubMed
Wong S, Oza A, Brierly J, et al. Phase I trial of Gemcitabine and escalating dose radiation therapy in patients with pancreatic carcinoma. Proc of ASCO 2000; 19: abst #1041.
Kudrimoti M, Regine W, Hanna N, Mohiuuddin M. Concurrent gemcitabine and radiation in the treatment of advanced unresectable GI malignancy: A phase I/II study. Proc ASCO 1999; 18:242a.
Fields MT, Eisbruch A, Normolle D, et al. Radiosensitization produced in vivo by once- vs. twice-weekly 2′2′-difluoro-2′-deoxycytidine (gemcitabine). Internat J Radiat Oncol Biol Phys 2000; 47(3): 785–791.CrossRef
Abad A, Arellano A, Brunet J, et al. Gemcitabine plus radiotherapy in stage II–III pancreatic cancer: A phase I trial. Proc of the 23rd Congress of the European Society for Medical Oncology 1998: abst #253.
Hoffman J, McGinn C, Ross E, et al. A phase I trial of preoperative gemcitabine and radiotherapy followed by post-operative gemcitabine for patients with localized, resectable, pancreatic adenocarcinoma. Cancer Invest 1999; 17(S1): 30–32.
- Toxicity and efficacy of concurrent gemcitabine and radiotherapy for locally advanced pancreatic cancer
International Journal of Pancreatology
Volume 29, Issue 1 , pp 9-18
- Cover Date
- Print ISSN
- Online ISSN
- Humana Press
- Additional Links
- Pancreatic neoplasms
- Industry Sectors
- C. H. Crane M.D. (1) (2)
- N. A. Janjan (1) (2)
- D. B. Evans (2) (3)
- R. A. Wolff (2) (4)
- M. T. Ballo (1) (2)
- L. Milas (2) (5)
- K. Mason (2) (5)
- C. Charnsangavej (2) (6)
- P. W. T. Pisters (2) (3)
- J. E. Lee (2) (3)
- R. Lenzi (2) (4)
- J. N. Vauthey (2) (3)
- A. Wong (1) (2)
- T. Phan (1) (2)
- Q. Nguyen (1) (2)
- J. L. Abbruzzese (2) (4)
- Author Affiliations
- 1. Radiation Oncology, The University of Texas M.D. Anderson Cancer Center, USA
- 2. From the Pancreatic Tumor Study Group, The University of Texas M.D. Anderson Cancer Center, USA
- 3. Surgical Oncology, The University of Texas M.D. Anderson Cancer Center, USA
- 4. Gastrointestinal Medical Oncology, The University of Texas M.D. Anderson Cancer Center, USA
- 5. Experimental Radiation Oncology, The University of Texas M.D. Anderson Cancer Center, USA
- 6. Diagnostic Radiology, The University of Texas M.D. Anderson Cancer Center, USA