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Effect of Chemoradiotherapy with Gemcitabine and Cisplatin on Locoregional Control in Patients with Primary Inoperable Pancreatic Cancer

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Abstract

Gemcitabine sensitizes tumor cells to radiation and cisplatin and thereby enhances the cytotoxic effect of gemcitabine. Here we report the efficacy and toxicity of concurrent chemoradiation with gemcitabine and cisplatin in the treatment of patients with locally advanced, unresectable pancreatic cancer. A total of 47 patients (29 men, 18 women; median age 61 years) with histologically proven advanced pancreatic carcinoma were included in the study. They underwent chemotherapy with gemcitabine 300 mg/m2 and cisplatin 30 mg/m2 on days 1, 8, 22, and 29; concurrent radiation (45—50 Gy) was applied to the tumor and regional lymph nodes (1.8—2.0 Gy/fraction 5 days per week). Subsequent to chemoradiotherapy, treatment was continued with more two cycles of gemcitabine (1000 mg/m2) and cisplatin (50 mg/m2) applied on days 1 and 15 of a 4-week cycle. After completion of chemoradiotherapy, 9 patients (19.1%) achieved a complete response and 23 patients (48.9%) a partial response, for an overall response rate of 68%. The lesions were considered resectable in 27 patients, and 25 of the 27 patients underwent laparotomy. The other 20 patients underwent a definitive pancreatic resection. Altogether, 13 patients had negative surgical margins. With a median follow-up of 25.7 months (range 12.7—38.7 months) after completion of chemoradiation, distant metastasis had occurred in 23 patients and local recurrence in only 4 of 44 patients (8.5%). the median progression-free survival was 7.8 months (range 6.2—9.4 months). The median survival amounted to 10.7 months (range 8.4—13.0 months) for all patients, whereas it was prolonged to 24.2 months (range 6.8—41.7 months) for those undergoing R0 resection. The main toxicities associated with chemoradiation included grade 3/4 leukopenia (68% of patients) and thrombocytopenia (61%). Episodes of cholangitis were observed in 11 patients. We concluded that gemcitabine and cisplatin can safely be combined with external beam radiation. This preoperative treatment approach is highly effective and appears to improve survival in patients whose tumors are rendered completely resectable.

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References

  1. DM Kelly IS Benjamin (1995) ArticleTitlePancreatic carcinoma Ann. Oncol. 6 19–28 Occurrence Handle1:STN:280:ByqB38njtlw%3D Occurrence Handle7536026

    CAS  PubMed  Google Scholar 

  2. SL Parker T Tong S Bolden et al. (1996) ArticleTitleCancer statistics CA Cancer J. Clin. 46 5–27 Occurrence Handle1:STN:280:BymC2czisFw%3D Occurrence Handle8548526

    CAS  PubMed  Google Scholar 

  3. InstitutionalAuthorNameGastrointestinal Tumor Study Group (1981) ArticleTitleTherapy 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 Cancer 48 1705–1710

    Google Scholar 

  4. InstitutionalAuthorNameGastrointestinal Tumor Study Group (1988) ArticleTitleTreatment of locally unresectable carcinoma of the pancreas: comparison of combined-modality therapy (chemotherapy plus radiotherapy) to chemotherapy alone J. Natl. Cancer Inst. 23 213–219

    Google Scholar 

  5. T Brunner G Grabenbauer U Baum et al. (2000) ArticleTitleAdjuvant and neoadjuvant radiochemotherapy in ductal pancreatic carcinoma Strahlenther. Onkol. 6 265–273 Occurrence Handle10.1007/s000660050008

    Article  Google Scholar 

  6. JM Jessup G Steele SuffixJr RJ Mayer et al. (1993) ArticleTitleNeoadjuvant therapy for unresectable pancreatic adenocarcinoma Arch. Surg. 128 559–564 Occurrence Handle1:STN:280:ByyB2MnnsFc%3D Occurrence Handle8098206

    CAS  PubMed  Google Scholar 

  7. MV Pilepich HH Miller (1980) ArticleTitlePreoperative irradiation in carcinoma of the pancreas Cancer 46 1945–1949 Occurrence Handle1:STN:280:Bi6D2c7pslM%3D Occurrence Handle7427900

    CAS  PubMed  Google Scholar 

  8. HA Burris SuffixIII MJ Moore J Andersen (1997) ArticleTitleImprovements in survival and clinical benefit with gemcitabine as first-line therapy for patients with advanced pancreas cancer: a randomized trial J. Clin. Oncol. 15 2403–2413 Occurrence Handle1:CAS:528:DyaK2sXlsFKksLY%3D Occurrence Handle9196156

    CAS  PubMed  Google Scholar 

  9. J Carmichael U Fink RC Russell et al. (1996) ArticleTitlePhase II study of gemcitabine in patients with advanced pancreatic cancer Br. J. Cancer 73 101–105 Occurrence Handle1:CAS:528:DyaK28Xht12iurc%3D Occurrence Handle8554969

    CAS  PubMed  Google Scholar 

  10. ES Casper MR Green DP Kelsen et al. (1994) ArticleTitlePhase II trial of gemcitabine (2,2’-difluorodeoxycytidine) in patients with adenocarcinoma of the pancreas Invest. New Drugs 12 29–34 Occurrence Handle1:STN:280:ByqD2cbivV0%3D Occurrence Handle7960602

    CAS  PubMed  Google Scholar 

  11. TS Lawrence EY Chang TM Hahn et al. (1996) ArticleTitleRadiosensitization of pancreatic cancer cells by 2’,2’-difluoro-2’-deoxycytidine Int. J. Radiat. Oncol. Biol. Phys. 34 867–872 Occurrence Handle10.1016/0360-3016(95)02134-5 Occurrence Handle1:CAS:528:DyaK28XisVCitrk%3D Occurrence Handle8598364

    Article  CAS  PubMed  Google Scholar 

  12. S Mose M Karapetian L Jüling-Pohlit et al. (1999) ArticleTitleVerstôrkung der radiotherapeutischen Wirkung auf HeLa-Zellen durch Gemcitabine Strahlenther. Onkol. 175 78–83 Occurrence Handle1:STN:280:DyaK1M7msVGgtQ%3D%3D Occurrence Handle10065143

    CAS  PubMed  Google Scholar 

  13. AM Bergman VW Ruiz van Haperen G Veerman et al. (1996) ArticleTitleSynergistic interaction between cisplatin and gemcitabine in vitro Clin. Cancer Res. 2 521–530 Occurrence Handle1:CAS:528:DyaK28XitVymu7Y%3D Occurrence Handle9816199

    CAS  PubMed  Google Scholar 

  14. V Heinemann (2002) ArticleTitleGemcitabine-based combination treatment of pancreatic cancer Semin. Oncol. 29 25–35 Occurrence Handle10.1053/sonc.2002.30749 Occurrence Handle1:CAS:528:DC%2BD38XislOjtL4%3D

    Article  CAS  Google Scholar 

  15. PA Philip M Zalupski V Vaitkevicius et al. (1999) ArticleTitlePhase II study of gemcitabine and cisplatinum in advanced or metastatic pancreatic cancer Proc. Am. Soc. Clin. Oncol. 18 A274

    Google Scholar 

  16. H Snady H Bruckner A Cooperman et al. (2000) ArticleTitleSurvival advantage of combined chemoradiotherapy compared with resection as the initial treatment of patients with regional pancreatic carcinoma: an outcomes trial Cancer 89 314–327 Occurrence Handle10.1002/1097-0142(20000715)89:2<314::AID-CNCR16>3.0.CO;2-V Occurrence Handle1:STN:280:DC%2BD3czptlSjtg%3D%3D Occurrence Handle10918161

    Article  CAS  PubMed  Google Scholar 

  17. FR Spitz JL Abbruzzese JE Lee et al. (1997) ArticleTitlePreoperative and postoperative chemoradiation strategies in patients treated with pancreaticoduodenectomy for adenocarcinoma of the pancreas J. Clin. Oncol. 15 928–937 Occurrence Handle1:STN:280:ByiB3MzosVU%3D Occurrence Handle9060530

    CAS  PubMed  Google Scholar 

  18. V Magnin V Moutardier MH Giovannini et al. (2003) ArticleTitleNeoadjuvant preoperative chemoradiation in patients with pancreatic cancer Int. J. Radiat. Oncol. Biol. Phys. 55 1300–1304 Occurrence Handle10.1016/S0360-3016(02)04157-3 Occurrence Handle12654441

    Article  PubMed  Google Scholar 

  19. RR White HI Hurwitz MA Morse et al. (2001) ArticleTitleNeoadjuvant chemoradiation for localized adenocarcinoma of the pancreas Ann. Surg. Oncol. 8 758–765 Occurrence Handle10.1245/aso.2001.8.10.758 Occurrence Handle1:STN:280:DC%2BD38%2FkvVygug%3D%3D Occurrence Handle11776488

    Article  CAS  PubMed  Google Scholar 

  20. ML Rothenberg MJ Moore MC Cripps et al. (1996) ArticleTitleA phase II trial of gemcitabine in patients with 5-FU-refractory pancreas cancer Ann. Oncol. 7 347–353 Occurrence Handle1:STN:280:BymA1MbktlY%3D Occurrence Handle8805925

    CAS  PubMed  Google Scholar 

  21. AW Blackstock SA Bernard F Richards et al. (1999) ArticleTitlePhase I trial of twice-weekly gemcitabine and concurrent radiation in patients with advanced pancreatic cancer J. Clin. Oncol. 17 2208–2212 Occurrence Handle1:CAS:528:DyaK1MXkvVSmurk%3D Occurrence Handle10561277

    CAS  PubMed  Google Scholar 

  22. R Epelbaum E Rosenblatt S Nasrallah et al. (2000) ArticleTitleA phase II study of gemcitabine (Gem) combined with radiation therapy (RT) in patients with localized, unresectable pancreatic cancer Proc. Am. Soc. Clin. Oncol. 19 A1029

    Google Scholar 

  23. JP Hoffman CJ McGinn C Szarka et al. (1998) ArticleTitleA phase I study of preoperative gemcitabine (GEM) with radiation therapy (RT) followed by postoperative GEM for patients with localized, resectable pancreatic adenocarcinoma (PaC) Proc. Am. Soc. Clin. Oncol. 17 A1090

    Google Scholar 

  24. M Kudrimoti W Regine W John et al. (1999) ArticleTitleConcurrent infusional gemcitabine and radiation in the treatment of advanced unresectable GI malignancy: a phase I/II study Proc. Am. Soc. Clin. Oncol. 18 A928

    Google Scholar 

  25. U Maurer P Stegmeier R Bolte et al. (1999) ArticleTitleGemcitabine (G) in combination radiation therapy (RT) in stage III-IV pancreatic cancer: first results of a current phase I study Eur. J. Cancer 35 A544 Occurrence Handle10.1016/S0959-8049(99)80972-1

    Article  Google Scholar 

  26. CJ McGinn DC Smith CE Szarka et al. (1998) ArticleTitleA phase I study of gemcitabine (GEM) in combination with radiation therapy (RT) in patients with localized, unresectable pancreatic cancer Proc. Am. Soc. Clin. Oncol. 17 A1014

    Google Scholar 

  27. J Reyes-Vidal P Rodriguez J Reyes et al. (2000) ArticleTitleChemoradiation therapy with gemcitabine (Gem) in advanced pancreatic cancer Proc. Am. Soc. Clin. Oncol. 19 A1183

    Google Scholar 

  28. R Wilkowski V Heinemann H Rau (2000) ArticleTitleRadiochemotherapy including gemcitabine and 5-fluorouracil for treatment of locally advanced pancreatic cancer Proc. Am. Soc. Clin. Oncol. 19 A1078

    Google Scholar 

  29. A Yavuz F Aydin M Yavuz et al. (2000) ArticleTitleA phase I trial of radiation therapy (RT) plus concurrent fixed dose amifostine (Ami) with escalating doses of twice-weekly gemcitabine in advanced pancreatic cancer Proc. Am. Soc. Clin. Oncol. 19 A1105

    Google Scholar 

  30. SM Lange ParticleDe CJ Groeningen Particlevan OW Meijer et al. (2002) ArticleTitleGemcitabine-radiotherapy in patients with locally advanced pancreatic cancer Eur. J. Cancer 38 1212–1217 Occurrence Handle10.1016/S0959-8049(02)00076-X Occurrence Handle12044508

    Article  PubMed  Google Scholar 

  31. M Ikeda S Okada K Tokuuye et al. (2002) ArticleTitleA phase I trial of weekly gemcitabine and concurrent radiotherapy in patients with locally advanced pancreatic cancer Br. J. Cancer 86 1551–1554 Occurrence Handle10.1038/sj.bjc.6600256 Occurrence Handle1:CAS:528:DC%2BD38XkvVaitb4%3D Occurrence Handle12085203

    Article  CAS  PubMed  Google Scholar 

  32. TB Brunner GG Grabenbauer P Klein et al. (2003) ArticleTitlePhase I trial of strictly time-scheduled gemcitabine and cisplatin with concurrent radiotherapy in patients with locally advanced pancreatic cancer Int. J. Radiat. Oncol. Biol. Phys. 55 144–153 Occurrence Handle10.1016/S0360-3016(02)03818-X Occurrence Handle1:CAS:528:DC%2BD38XpslSltr0%3D Occurrence Handle12504047

    Article  CAS  PubMed  Google Scholar 

  33. MS Talamonti PJ Catalano DJ Vaughn et al. (2000) ArticleTitleEastern Cooperative Oncology Group phase I trial of protracted venous infusion fluorouracil plus weekly gemcitabine with concurrent radiation therapy in patients with locally advanced pancreas cancer: a regimen with unexpected early toxicity J. Clin. Oncol. 18 3384–3389 Occurrence Handle1:CAS:528:DC%2BD3cXnslWjsr4%3D Occurrence Handle11013279

    CAS  PubMed  Google Scholar 

  34. CH Crane NA Janjan DB Evans et al. (2001) ArticleTitleToxicity and efficacy of concurrent gemcitabine and radiotherapy for locally advanced pancreatic cancer Int. J. Pancreatol. 29 9–18 Occurrence Handle10.1385/IJGC:29:1:09 Occurrence Handle1:CAS:528:DC%2BD3MXmvFKnt7g%3D Occurrence Handle11560155

    Article  CAS  PubMed  Google Scholar 

  35. R Wilkowski C Stoffregen H-G Rau et al. (2001) ArticleTitleChemoradiation with gemcitabine (G) in primary inoperable pancreatic cancer Proc. Am. Soc. Clin. Oncol. 20 A2317

    Google Scholar 

  36. CJ McGinn MM Zalupski I Shureiqi et al. (2001) ArticleTitlePhase I trial of radiation dose escalation with concurrent weekly full-dose gemcitabine in patients with advanced pancreatic cancer J. Clin. Oncol. 19 4202–4208 Occurrence Handle1:CAS:528:DC%2BD38XhslWqtg%3D%3D Occurrence Handle11709563

    CAS  PubMed  Google Scholar 

  37. E Bajetta M Bartolomeo ParticleDi SC Stani et al. (1999) ArticleTitleChemoradiotherapy as preoperative treatment in locally advanced unresectable pancreatic cancer patients: results of a feasibility study Int. J. Radiat. Oncol. Biol. Phys. 45 285–289 Occurrence Handle10.1016/S0360-3016(99)00205-9 Occurrence Handle1:CAS:528:DyaK1MXls12ntb0%3D Occurrence Handle10487547

    Article  CAS  PubMed  Google Scholar 

  38. Mawdsley S, Hall M, Glynne-Jones R. Locally advanced pancreatic cancer treated with radiation and 5-fluorouracil. Clin. Oncol. (R. Coll. Radiol.) 2002;14:308—312

    Google Scholar 

  39. MF Osti AM Costa F Bianciardi et al. (2001) ArticleTitleConcomitant radiotherapy with protracted 5-fluorouracil infusion in locally advanced carcinoma of the pancreas: a phase II study Tumori 87 398–401 Occurrence Handle1:CAS:528:DC%2BD38XjvFGltrg%3D Occurrence Handle11989594

    CAS  PubMed  Google Scholar 

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Authors and Affiliations

  1. Klinik und Poliklinik für Strahlentherapie und Radioonkologie, Klinikum Grosshadern der LMU München, Marchioninistrasse 15, 81377, München, Germany

    Ralf Wilkowski M.D. & Martin Thoma M.D.

  2. Chirurgische Klinik und Poliklinik, Klinikum Grosshadern der LMU München, Marchioninistrasse 15, 81377, München, Germany

    Rolf Schauer M.D.

  3. Medizinische Klinik II, Klinikum Grosshadern der LMU München, Marchioninistrasse 15, 81377, München, Germany

    Andreas Wagner M.D.

  4. Medizinische Klinik III, Klinikum Grosshadern der LMU München, Marchioninistrasse 15, 81377, München, Germany

    Volker Heinemann M.D.

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  1. Ralf Wilkowski M.D.
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Correspondence to Ralf Wilkowski M.D..

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Wilkowski, R., Thoma, M., Schauer, R. et al. Effect of Chemoradiotherapy with Gemcitabine and Cisplatin on Locoregional Control in Patients with Primary Inoperable Pancreatic Cancer. World J. Surg. 28, 1011–1018 (2004). https://doi.org/10.1007/s00268-004-7338-z

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