Advanced search
Publication Cover
Expert Opinion on Investigational Drugs Volume 11, 2002 - Issue 1
Submit an article Journal homepage
36
Views
8
CrossRef citations to date
0
Altmetric
Miscellaneous

The role of adjuvant therapy for pancreatic cancer

Mark Hartley Department of Surgery, University of Liverpool, 5th Floor UCD Building, Daulby Street, Liverpool, L69 3GA, UK, Tel: +44 151 706 4170; Fax: +44 151 706 5826
,
Paula Ghaneh Department of Surgery, University of Liverpool, 5th Floor UCD Building, Daulby Street, Liverpool, L69 3GA, UK, Tel: +44 151 706 4170; Fax: +44 151 706 5826
,
Robert Sutton Department of Surgery, University of Liverpool, 5th Floor UCD Building, Daulby Street, Liverpool, L69 3GA, UK, Tel: +44 151 706 4170; Fax: +44 151 706 5826
,
John P Neoptolemos Department of Surgery, University of Liverpool, 5th Floor UCD Building, Daulby Street, Liverpool, L69 3GA, UK, Tel: +44 151 706 4170; Fax: +44 151 706 5826
&
Conor J Magee Department of Surgery, University of Liverpool, 5th Floor UCD Building, Daulby Street, Liverpool, L69 3GA, UK, Tel: +44 151 706 4170; Fax: +44 151 706 5826
Pages 87-107 | Published online: 24 Feb 2005

Bibliography

  • PARKIN DM, BRAY FI, DEVESA SS: Cancer burden in the year 2000. The global picture. Eur. I Cancer (2001) (Suppl. 37) 8:4-66.
  • GREENLEE RT, HILL-HARMON MB, MURRAY T et al.: Cancer statistics, 2001. CA Cancer J. Clin. (2001) 51(l):15–36.
  • COLEMAN MP, BABB P, DAMIECKI P: Cancer surival trends in England and wales, 1971–1995: deprivation and NHS region. London: The Stationary Office, 1999.
  • BRAMHALL SR, ALLUM WH, JONES AG et al.: Treatment and survival in 13,560 patients with pancreatic cancer, and incidence of the disease, in the West Midlands: an epidemiological study. Br. Surg. (1995) 82(1):111–115.
  • WELCH HG, SCHWARTZ LM, WOLOSHIN S: Are increasing 5-year survival rates evidence of success against cancer?JAMA (2000) 283(22):2975–2978.
  • MAGEE CJ, GREENHALF WG, HOWES N et al.: Molecular pathogenesis of pancreatic adenocarcinoma and clinical implications. Surg.Oncol. (2001) In press.
  • TREDE M, SCHWALL G, SAEGER HD: Survival after pancreatoduodenectomy. 118 consecutive resections without an operative mortality. Ann. Surg. (1990) 211(4):447–458.
  • SOHN TA, YEO CJ, CAMERON JL etal.: Resected adenocarcinoma of the pancreas-616 patients: results, outcomes, and prognostic indicators. j Gastrointest. Surg. (2000) 4(6):567–579.
  • ALLEMA JH, REINDERS ME, VAN GULIK TM et al.: Prognostic factors for survival after pancreaticoduodenectomy for patients with carcinoma of the pancreatic head region. Cancer (1995) 75(8):2069–2076.
  • MOSCA F, GIULIANOTTI PC, BALESTRACCI T et al.: Long-term survival in pancreatic cancer: pylorus-preserving versus Whipple pancreatoduodenectomy. Surgery (1997) 122(3):553–566.
  • YEO CJ, ABRAMS RA, GROCHOW LB et al.: Pancreaticoduodenectomy for pancreatic adenocarcinoma: postoperative adjuvant chemoradiation improves survival. A prospective, single- institution experience. Ann. Surg. (1997) 225(5):621–633; discussion 633–636.
  • ••Large single series study describingexperience with resection for pancreatic cancer and the selective use of combination adjuvant therapy. The results of aggressive combination adjuvant therapy (including chemoradiotherapy) no better or worse than adjuvant chemotherapy described in the ESPAC-1 Trial [136].
  • NITECKI SS, SARR MG, COLBY TV et al.: Long-term survival after resection for ductal adenocarcinoma of the pancreas. Is it really improving? Ann. Surg. (1995) 221(1): 59–66.
  • GEER RJ, BRENNAN MF: Prognostic indicators for survival after resection of pancreatic adenocarcinoma. Am. j Surg. (1993) 165(1):68–72; discussion 72–73.
  • NEOPTOLEMOS JP, RUSSELL RC, BRAMHALL S et al.: Low mortality following resection for pancreatic and periampullary tumours in 1026 patients: UK survey of specialist pancreatic units. UK Pancreatic Cancer Group. Br I Surg. (1997) 84(10):1370–1376.
  • •Results of resection for pancreatic cancer in the UK. Low post-operative mortality compared to the very high mortality observed in non-specialist units described in reference [3].
  • ISHIKAWA 0, OHHIGASHI H, SASAKI Y etal.: Practical usefulness of lymphatic and connective tissue clearance for the carcinoma of the pancreas head. Ann. Surg. (1988) 208(2):215–220.
  • NAGAKAWA T, NAGAMORI M, FUTAKAMI F et al.: Results of extensive surgery for pancreatic carcinoma. Cancer (1996) 77(4):640–645.
  • SPERTI C, PASQUALI C, PICCOLI A et al.: Recurrence after resection for ductal adenocarcinoma of the pancreas. World j Surg. (1997) 21(2):195–200.
  • OHIGASHI H, ISHIKAWA 0, TAMURA S et al.: Pancreatic invasion as the prognostic indicator of duodenal adenocarcinoma treated by pancreatoduodenectomy plus extended lymphadenectomy. Surgery (1998) 124(3):510–515.
  • NAKAO A, KANEKO T, TAKEDA S et al.: The role of extended radical operation for pancreatic cancer. Hepatogastroenterology (2001) 48(40):949–952.
  • PEDRAZZOLI S, DICARLO V, DIONIGI R etal.: Standard versus extended lymphadenectomy associated with pancreatoduodenectomy in the surgical treatment of adenocarcinoma of the head of the pancreas: a multicenter, prospective, randomized study. Lymphadenectomy Study Group. Ann. Surg. (1998) 228(4):508–517.
  • •To-date the only randomised controlled trial of extended lymphadenectomy in resected pancreatic cancer. No differences observed but probably underpowered.
  • YEO CJ, CAMERON JL, SOHN TA etal.: Pancreaticoduodenectomy with or without extended retroperitoneal lymphadenectomy for periampullary adenocarcinoma: comparison of morbidity and mortality and short-term outcome. Ann. Surg. (1999) 229(5):613–622; discussion 622–624.
  • SATAKE K, NISHIWAKI H, YOKOMATSU H et al.: Surgical curability and prognosis for standard versus extended resection for Ti carcinoma of the pancreas. Surg. Cynecol Obstet. (1992) 175(3):259–265.
  • MILLIKAN KW, DEZIEL DJ, SILVERSTEIN JC et al.: Prognostic factors associated with resectable adenocarcinoma of the head of the pancreas. Am. Surg. (1999) 65(7):618–623; discussion 623–624.
  • WILLETT CG, LEWANDROWSKI K, WARSHAW AL etal.: Resection margins in carcinoma of the head of the pancreas. Implications for radiation therapy. Ann. Surg. (1993) 217(2):144–148.
  • MAGISTRELLI E ANTINORI A, CRUCITTI A et al.: Prognostic factors after surgical resection for pancreatic carcinoma. Surg. Oiled. (2000) 74(1):36–40.
  • KAWESHA A, GHANEHP, ANDREN-SANDBERG A et al.: K-ras oncogene subtype mutations are associated with survival but not expression of p53, p16(INK4A), p21(WAF-1), cyclin D1, erbB-2 and erbB-3 in resected pancreatic ductal adenocarcinoma. Int.j Cancer (2000) 89(6): 469–474.
  • •Survival in resected pancreatic cancer shown to correlate with the KRAS mutation sub-type.
  • FRIESS H, LU Z, ANDREN-SANDBERG A et al: Moderate activation of the apoptosis inhibitor bc1-xL worsens the prognosis in pancreatic cancer. Ann. Surg. (1998) 228(6):780–787.
  • GRIFFIN JF, SMALLEY SR, JEWELL W et al.: Patterns of failure after curative resection of pancreatic carcinoma. Cancer (1990) 66(1):56–61.
  • AMIKURA K, KOBARI M, MATSUNO S: The time of occurrence of liver metastasis in carcinoma of the pancreas. Int. j Pancreatol (1995) 17(2):139–146.
  • PEDRAZZOLI S, BEGER HG, OBERTOP et al.: A surgical and pathological based classification of resective treatment of pancreatic cancer. Summary of an international workshop on surgical procedures in pancreatic cancer. Dig. Surg. (1999) 16(4):337–345.
  • •Defines the different types of pancreatic cancer by radicality.
  • JONES L, RUSSELL C, MOSCA F et al.: Standard Kausch-Whipple pancreatoduodenectomy. Dig. Surg. (1999) 16 (4):297–304.
  • •Defines the standard operation for resection of cancer of the head of the pancreas.
  • SEILER CA, WAGNER M, SAD OWSKI C et al.: Randomized prospective trial of pylorus-preserving vs. Classic duodenopancreatectomy (Whipple procedure): initial clinical results. Castrointest. Surg. (2000) 4(5):443–452.
  • KARPOFF HM, KLIMSTRA DS, BRENNAN MF et al.: Results of total pancreatectomy for adenocarcinoma of the pancreas. Arch. Surg. (2001) 136(1):44–47; discussion 48.
  • THERASSE E ARBUCK SG, EISENHAUER EA et al.: New guidelines to evaluate the response to treatment in solid tumors. European Organization for Research and Treatment of Cancer, National Cancer Institute of the United States, National Cancer Institute of Canada. j Natl. Cancer Inst. (2000) 92(3):205–216.
  • ••The new RECIST recommendations fordetermining response to therapy in solid tumours.
  • HALM U, SCHUMANN T, SCHIEFKE I et al: Decrease of CA 19-9 during chemotherapy with gemcitabine predicts survival time in patients with advanced pancreatic cancer. Br j Cancer (2000) 82(5):1013–1016.
  • HEINEMANN V, SCHERMULY MM, STIEBER P et al: CA19-9: a pedictor of response in pancreatic cancer treated with gemcitabine and cisplatin. Anti-Cancer Res. (1999) 19(4A):2433–2435.
  • KLAPDOR R, SEUTTER E, LANG-POLCKOW EM et al: Locoregional/ systemic chemotherapy of locally advanced/ metastasized pancreatic cancer with a combination of mitomycin-C and gemcitabine and simultaneous follow-up by imaging methods and tumor markers. Anti-Cancer Res. (1999) 19(4A):2459–2469.
  • LINK KH, LEDER G, PILLASCH J etal.: In vitro concentration response studies and in vitro Phase II tests as the experimental basis for regional chemotherapeutic protocols. Salmi]. Surg. Oncol (1998) 14(3):189–201.
  • HAYCOX A, LOMBARD M, NEOPTOLEMOS J etal.: Review article: current treatment and optimal patient management in pancreatic cancer. Aliment Pharmacol Ther (1998) 12(10):949–964.
  • CROWN J, CASPER ES, BOTET J etal.: Lack of efficacy of high-dose leucovorin and fluorouracil in patients with advanced pancreatic adenocarcinoma. j Clir]. Oncol (1991) 9(9):1682–1686.
  • RUBIN J, GALLAGHER JG, SCHROEDER G et al: Phase II trials of 5-fluorouracil and leucovorin in patients with metastatic gastric or pancreatic carcinoma. Cancer (1996) 78(9):1888–1891.
  • Efficacy of intravenous continuous infusion of fluorouracil compared with bolus administration in advanced colorectal cancer. Meta-analysis Group In Cancer. I CM]. Oiled. (1998) 16(1):301–308.
  • MAISEY N, CHAU I, NORMAN A: Protracted venous infusion 5-fluorouracil woth or without mitomycin C in advanced pancreatic cancer. American Society of Clinical Oncology Annual Meeting, (2001).
  • CARTWRIGHT T: A Phase 2 trial of Xeloda (Capecitabine) in advanced or metastatic pancreatic cancer. American Society of Clinical Oncology Annual Meeting, (2000).
  • ELZA-BROWN K, DEES EC, AC W: A Phase I study of capecitabine and weekily paclitaxel in advanced solid tumours. American Society of Clinical Oncology Annual Meeting, (2000).
  • HERTEL LW, BODER GB, KROIN JS et al.: Evaluation of the antitumor activity of gemcitabine (2',2'-difluoro-2'-deoxycytidine). Cancer Res. (1990) 50(14):4417–4422.
  • LAWRENCE TS, CHANG EY, HAHN TM et al.: Radiosensitization of pancreatic cancer cells by 2',2-difluoro-2'- deoxycytidine. Int. Radiat. Oncol. Biol. Phys. (1996) 34(4):867–872.
  • MALLINSON CN, RAKE MO, COCKING JB et al.: Chemotherapy in pancreatic cancer: results of a controlled, prospective, randomised, multicentre trial. Br Med. J(1980) 281(6255):1589–1591.
  • FREY C, TWOMEY P, KEEHN R et al: Randomized study of 5-FU and CCNU in pancreatic cancer: report of the Veterans Administration Surgical Adjuvant Cancer Chemotherapy Study Group. Cancer (1981) 47(1):27–31.
  • PALMER KR, KERR M, KNOWLES G et al.: Chemotherapy prolongs survival in inoperable pancreatic carcinoma. Br I Surg. (1994) 81(6):882–885.
  • •Randomised controlled trial of chemotherapy versus no treatment in advanced pancreatic cancer, showing the survival benefit for chemotherapy.
  • GLIMELIUS B, HOFFMAN K, SODEN P-0 et al.: Chemotherapy improves survival and quality of life in advanced pancreatic and binary cancer. Ann. amyl 1996; 7: 593–600.
  • •Randomised controlled trial of chemotherapy versus no treatment, showing the survival benefit for chemotherapy in advanced pancreatic cancer.
  • CULLINAN S, MOERTEL CG, WIEAND HS et al.: A Phase III trial on the therapy of advanced pancreatic carcinoma. Evaluations of the Mallinson regimen and combined 5-fluorouracil, doxorubicin, and cisplatin. Cancer (1990) 65(10):2207–2212.
  • ••A large randomised trial in advancepancreatic cancer that demonstrated that single agent 5-FU was less toxic and with equal survival than two other 5-FU-based combination chemotherapy regimens.
  • PERMERT J, HAFSTROM L, NYGREN P et al.: A systematic overview of chemotherapy effects in pancreatic cancer. Acta Oncol. (2001) 40(2-3):361–370.
  • BURRIS HA, III, 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. Oncol. (1997) 15(6):2403–2413.
  • ••The only randomised controlled trial ofgemcitabine in a head to head comparison with another single agent in pancreatic cancer. Showed an apparent better survival benefit of - 5weeks for gemcitabine compared to bolus 5-FU in advanced pancreatic cancer.
  • SAUER-HEILBORN A, KATH R, SCHNEIDER CP et al.: Severe non-haematological toxicity after treatment with gemcitabine. I Cancer Res. Clin. Oncol. (1999) 125(10:637–640.
  • LOU VET C, HAMMEL E ANDRE T: Multicentre Phase II study in advanced pancreatic adenocarcinoma patients treated with a combination of leucovorin, 5-FU bolus and infusion and gemcitabine (FOLFUGEM regimen). American Society of Clinical Oncology Annual Meeting, (1999).
  • OETTLE H, ARNING M, PELZER U et al.: A Phase II trial of gemcitabine in combination with 5-fluorouracil (24- hour) and folinic acid in patients with chemonaive advanced pancreatic cancer. Ann. arca (2000) 11(10):1267–1272.
  • TALAMONTI MS, CATALANO PJ, VAUGHN DJ et al.: Eastern 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 Chit. Oncol. (2000) 18(19)3384–3389.
  • COLLUCI G, GIULIANI E RICCARDI F: Gemcitabine alone or with cis-platin in advanced pancreatic cancer: prelininary results of a randomised study of the Southern Italy Oncology Group. ASCO, 1998.
  • PHILIP PA, ZALUPSKI MM, VAITKEVICIUS VK et al.: Phase II study of gemcitabine and cisplatin in the treatment of patients with advanced pancreatic carcinoma. Cancer (2001) 92(3):569–577.
  • GUNDERSON LL, MARTIN JK, KVOLS LK etal.: Intraoperative and external beam irradiation +1-5-FU for locally advanced pancreatic cancer. Int. j Radiat. Oncol. Biol. Phys. (1987) 13(3):319–329.
  • TISDALE BA, PARIS KJ, LINDBERG RD et al.: Radiation therapy for pancreatic cancer: a retrospective study of the University of Louisville experience. South Med. J. (1995) 88(7):741–744.
  • IKEDA M, OKADA S, TOKUUYE K et al.:Prognostic factors in patients with locally advanced pancreatic carcinoma receiving chemoradiotherapy. Cancer (2001) 91(3):490–495.
  • SAFRAN H, MOORE T, IANNITTI D et al.: Paclitaxel and concurrent radiation for locally advanced pancreatic cancer. Int. Radiat. arca Biol. Phys. (2001) 49(5):1275–1279.
  • CEHA HM, VAN TIENHOVEN G, GOUMA DJ et al.: Feasibility and efficacy of high dose conformal radiotherapy for patients with locally advanced pancreatic carcinoma. Cancer (2000) 89(11)2222–2229.
  • GARTON GR, GUNDERSON LL, NAGORNEY DM etal.: High-dose preoperative external beam and intraoperative irradiation for locally advanced pancreatic cancer. Int. j Radiat. Oncol. Biol. Phys. (1993) 27(5):1153–1157.
  • WILLETT CG, WARSHAW AL: Intraoperative radiation therapy of pancreatic cancer. In: The Pancreas. Beger H, Warshaw AL, Buchler M et al. (Eds.). Blackwell Science Limited, Oxford, UK (1998).
  • 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.
  • ••Landmark paper from GITSG showing thatfollow-on chemotherapy after chemoradiotherapy was superior to high dose chemoradiotherapy alone in advanced pancreatic cancer. Did not show that chemoradiotherapy was necessary in addition to repeated cycles of 5-FU to produce improved survival compared to chemoradiotherapy alone.
  • PROTT FJ, SCHONEKAES K, PREUSSER P etal.: Combined modality treatment with accelerated radiotherapy and chemotherapy in patients with locally advanced inoperable carcinoma of the pancreas: results of a feasibility study. Br j Cancer (1997) 75(4):597–601.
  • YASUE M, SAKAMOTO J, YASUI K: A randomised trial of intraoperative radiation therapy (TORT) vs. IORT plus chemotherapy (MTX-5FU) for adenocarcinoma of the pancreas. Cancer Res. Ther. Control (1993) 3:283.
  • KACHNIC LA, SHAW JE, MANNING MA et al.: Gemcitabine following radiotherapy with concurrent 5-fluorouracil for nonmetastatic adenocarcinoma of the pancreas. Int. J. Cancer (2001) 96(2):132–139.
  • KORNEK GV, POTTER R, SELZER E et al.: Combined radiochemotherapy of locally advanced unresectable pancreatic adenocarcinoma with mitomycin C plus 24-hour continuous infusional gemcitabine. Radiat. arca Biol. Phys. (2001) 49(3):665–671.
  • AIGNER KR, MULLER H, BESSERMANN R: Intra-arterial chemotherapy with MMC, CDDP and 5-FU for non-resectable pancreatic cancer- A Phase II study. Reg. Cancer Treat. (1990) 3:1–6.
  • MUCHMORE JH, PRESLAN JE, GEORGE WJ: Regional chemotherapy for inoperable pancreatic carcinoma. Cancer (1996) 78(3 Suppl):664–673.
  • AIGNER KR, GAILHOFER S, KOPP S: Regional versus systemic chemotherapy for advanced pancreatic cancer: a randomized study. Hepatogastroenterology (1998) 45(22):1125–1129.
  • LIU M, BRYANT MS, CHEN J et al.: Antitumor activity of SCH 66336, an orally bioavailable tricyclic inhibitor of farnesyl protein transferase, in human tumor xenograft models and wap-ras transgenic mice. Cancer Res. (1998) 58(20:4947–4956.
  • ITO T, KAWATA S, TAMURA S et al.: Suppression of human pancreatic cancer growth in BALB/c nude mice by manumycin, a farnesyl:protein transferase inhibitor. bra. I Cancer Res. (1996) 87(2):113–116.
  • WHYTE DB, KIRSCHMEIER P, HOCKENBERRY TN et al.: K- and N-Ras are geranylgeranylated in cells treated with farnesyl protein transferase inhibitors. I Biol. Chem. (1997) 272(22):14459–14464.
  • ROCHA LIMA CM, SHERMAN CA, BRESCIA FJ etal.: Irinotecanigemcitabine combination chemotherapy in pancreatic cancer. Oncology (Huntingt) (2001) 15(3 Suppl. 5):46–51.
  • RIVKIN S, BURRIS HA, III, GERSTEIN H et al.: A Phase II study of Rubitecan (RFS 2000, 9NC, 9-Nitro-20(S)-Camptothecin) in Patients with Refractory Pancreatic Cancer. American Sado, of Clinical Oncology Annual Meeting 2000, New Orleans, 2000.
  • HANAHAN D, WEINBERG RA: The hallmarks of cancer. Cell (2000) 100(1)57–70.
  • ••A state-of-the-art paper on the biologicalbasis of cancer.
  • BRAMHALL SR, STAMP GWH, DUNN J, LEMOINE NR, NEOPTOLEMOS JP: Expression of collagenase (MMP2), stromelysin (MMP3) and tissue inhibitor of the metalloproteinases (TIMP1) in pancreatic and ampullary disease. Br. Cancer (1996) 73:982–988.
  • BRAMHALL SR, NEOPTOLEMOS JP, STAMP GW et al.: Imbalance of expression of matrix metalloproteinases (MMPs) and tissue inhibitors of the matrix metalloproteinases (TIMPs) in human pancreatic carcinoma. j Pathol. (1997) 182(3):347–355.
  • JONES L, GHANEH P, HUMPHREYS M, NEOPTOLEMOS JP: The matrix metalloproteinases and their inhibitors in the treatment of pancreatic cancer. Ann. NY Acad. ScL (1999) 880:288–307.
  • EVANS JD, STARK A, JOHNSON CD et al.: A Phase II trial of marimastat in advanced pancreatic cancer. Br j Cancer (2001): In press.
  • BRAMHALL SR, ROSEMURGY A, BROWN PD et al.: Marimastat as first-line therapy for patients with unresectable pancreatic cancer: a randomized trial. ..J. Clin. Omni (2001) 19(15):3447–3455.
  • ••A randomised controlled trial suggestingthat high dose marimastat, a matrix metalloproteinase inhibitor, produces similar survival to that of gemcitabine in advanced pancreatic cancer.
  • ROBERTSON JF, WATSON SA, HARD CASTLE JD: Effect of gastrointestinal hormones and synthetic analogues on the growth of pancreatic cancer. Int.j Cancer (1995) 63(1):69–75.
  • WATSON SA, MICHAELI D, GRIMES S et al.: Gastrimmune raises antibodies that neutralize amidated and glycine- extended gastrin-17 and inhibit the growth of colon cancer. Cancer Res. (1996) 56(4):880–885.
  • WATSON SA, MICHAEL D, JUSTIN TA et al.: Pre-clinical evaluation of the Gastrimmune immunogen alone and in combination with 5-fluorouracilheucovorin in a rat colorectal cancer model. Int. j Cancer (1998) 75(6):873–877.
  • GILLIAM AD, HENWOOD M, WATSON SA et al: G17DT Therapy May Improve Survival of Patients with Advanced Pancreatic Carcinoma. ASCO 2001, San Francisco, 2001.
  • SEMENZA GL: Hypoxia-inducible factor I: master regulator of 02 homeostasis. Curr. Opin Genet. Dev. (1998) 8(5):588–594.
  • HOTZ HG, REBER HA, HOTZ B et al: Angiogenesis inhibitor TNP-470 reduces human pancreatic cancer growth. Castrointest. &mg. (2001) 5(2):131–138.
  • BERGERS G, JAVAHERIAN K, LO KM, FOLKMAN J, HANAHAN D: Effects of angiogenesis inhibitors on multistage carcinogenesis in mice. Science (1999) 284:808–812.
  • THOMAS DA, KANTARJIAN HM: Current role of thalidomide in cancer treatment. Curr. Opin. Omni (2000) 12(6):564–573.
  • PAZDUR R, LASSERE Y, DIAZ- CANTONE et al.: Phase I trials of uracil-tegafur (UFT) using 5 and 28 day administration schedules: demonstration of schedule-dependent toxicities. Anti-Cancer Drugs (1996) 7(7):728–733.
  • ROUGIER P, ADENIS A, DUCREUX Met al.:A Phase II study: docetaxel as first-line chemotherapy for advanced pancreatic adenocarcinoma. Eur. j Cancer (2000) 36(8):1016–1025.
  • SHERMAN WH, FINE RL: Combination gemcitabine and docetaxel therapy in advanced adenocarcinoma of the pancreas. Oncology (2001) 60(4):316–321.
  • CASCINU S, GASPARINI G, CATALANO V etal.: A Phase I-II study of gemcitabine and docetaxel in advanced pancreatic cancer: a report from the Italian Group for the Study of Digestive Tract Cancer (GISCAD). Ann. Omni (1999) 10(11):1377–1379.
  • STATHOPOULOS GP, MAVROUDIS D, TSAVARIS N et al.: Treatment of pancreatic cancer with a combination of docetaxel, gemcitabine and granulocyte colony-stimulating factor: a Phase II study of the Greek Cooperative Group for Pancreatic Cancer. Ann. Oncol. (2001) 12(1):101–103.
  • SLAMON DJ, LEYLAND-JONES B, SHAK S et al.: Use of chemotherapy plus a monoclonal antibody against HER2 for metastatic breast cancer that overexpresses HER2. N Engl. J Med. (2001) 344(11):783–792. Dm. SAFRAN H, RAMANATHAN RK, SCHWARTZ J et al: Herceptin and Gemcitabine for Metastatic Pancreatic Cancers that Overexpress Her-21 neu. ASCO, San Francisco, USA (2001). Dn. GJERTSEN MK, BUANES T, ROSSELAND AR et al.: Intradermal ras peptide vaccination with granulocyte-macrophage colony-stimulating factor as adjuvant: Clinical and immunological responses in patients with pancreatic adenocarcinoma.Cancer (2001)92(3):441–450.
  • SCHMIEGEL W, SCHMIELAU J, HENNE-BRUNS D et al.: Cytokine-mediated enhancement of epidermal growth factor receptor expression provides an immunological approach to the therapy of pancreatic cancer. Proc. Natl Acad. Sci. USA (1997) 94(23): 12622–12626.
  • ZISKE C, MARTEN A, SCHOTTKER B et al.: Resistance of pancreatic carcinoma cells is reversed by co-culturing NK- like T cells with dendritic cells pulsed with tumor-derived RNA and CA 19-9. Ma Ther. (2001) 3(1):54–60.
  • JAFFEE EM, HRUBAN RH, BIEDRZYCKI B etal.: Novel allogeneic granulocyte-macrophage colony-stimulating factor- secreting tumor vaccine for pancreatic cancer: a phase i trial of safety and immune activation. J. Clin. Omni (2001) 19(1):145–156. los. JAFFEE EM, ABRAMS R, CAMERON J et al.: A Phase I clinical trial of lethally irradiated allogeneic pancreatic tumor cells transfected with the GM-CSF gene for the treatment of pancreatic adenocarcinoma. Hum. Gene Ther. (1998) 9(13):1951–1971.
  • LEWIS JJ, JANETZKI S, LIVINGSTON PO etal.: Pilot trial of vaccination with autologous tumor-derived gp96 Heat Shock protein peptide Complex (HSPPC-96) in patients with resected pancreatic adenocarcinoma. American Socieo, of Clinical Oncology Annual Meeting (1999).
  • KITA K, SAITO S, MORIOKA CY et al.: Growth inhibition of human pancreatic cancer cell lines by anti-sense oligonucleotides specific to mutated K-ras genes. Intl Cancer (1999) 80(4):553–558. los. KELLEY JR, BROWN JM, FRASIER MM et al.: The cancer-associated Sm-like oncogene: a novel target for the gene therapy of pancreatic cancer. Surgery (2000) 128(2):353–360.
  • BOUVET M, BOLD RJ, LEE J et al: Adenovirus-mediated wild-type p53 tumor suppressor gene therapy induces apoptosis and suppresses growth of human pancreatic 104 cancer. Ann. Surg. Oncol. (1998) 5(8):681–688.
  • GHANEH P, GREENHALF W, HUMPHREYS M et al.: Adenovirus-mediated transfer of p53 and p16(INK4a) results in pancreatic cancer regression in vitro and in vivo. Gene Ther. (2001) 8(3):199–208.
  • KOBAYASHI S, SHIRASAWA H, SASHIYAMA H et aL:P16INK4a expression adenovirus vector to suppress pancreas cancer cell proliferation. Clin. Cancer Res. (1999) 5(12):4182–4185.
  • KASUYA H, NISHIYAMA Y, NOMOTO S et al.: Intraperitoneal delivery of hrR3 and ganciclovir prolongs survival in mice with disseminated pancreatic cancer. j Surg. Oncol. (1999) 72(3):136–141.
  • CARRIO M, ROMAGOSA A, MERCADE E et al.: Enhanced pancreatic tumor regression by a combination of adenovirus and retrovirus-mediated delivery of the herpes simplex virus thymidine kinase gene. Gene Ther. (1999) 6(4):547–553.
  • TANAKA S, IWAI M, HARADA Y et at.: Targeted killing of carcinoembryonic antigen (CEA)-producing cholangiocarcinoma cells by polyamidoamine dendrimer-mediated transfer of an Epstein-Barr virus (EBV)-based plasmid vector carrying the CEA promoter. Cancer Gene Ther. (2000) 7(9):1241–1250.
  • HUMPHREYS MJ, GHANEH E GREENHALF W et al.: Hepatic intra-arterial delivery of a retroviral vector expressing the cytosine deaminase gene, controlled by the CEA promoter and intraperitoneal treatment with 5-fluorocytosine suppresses growth of colorectal liver metastases. Gene Ther. (2001) 8(16):1241–1247.
  • MCNEISH IA, GREEN NK, GILLIGAN MG et al.: Virus directed enzyme prodrug therapy for ovarian and pancreatic cancer using retrovirally delivered E coil nitroreductase and CB1954. Gene Ther. (1998) 5(8):1061–1069.
  • GREEN NK, YOUNGS DJ, NEOPTOLEMOS JP et al.: Sensitization of colorectal and pancreatic cancer cell lines to the prodrug 5-(aziridin 1 yl) 2,4 dinitrobenzamide (CB1954) by retroviral transduction and expression of the E. coli nitroreductase gene. Cancer Gene Ther. (1997) 4(4):229–238.
  • LOHR M, HOFFMEYER A, KROGER Jet al.: Microencapsulated cell-mediated treatment of inoperable pancreatic carcinoma. Lancet (2001) 357(9268):1591–1592.
  • ••Demonstrates the proof of principle of gene therapy in advanced pancreatic cancer - in this case a GDEPT approach.
  • MOTOI F, SUNAMURA M, DING L et al.: Effective gene therapy for pancreatic cancer by cytokines mediated by restricted replication-competent adenovirus. Hum. Gene Ther. (2000) 11(2):223–235.
  • HECHT JT, BEDFORD R, ABBRUZZESE JL et al.: A Phase I/II trial of intratumoral endoscopic ultrasound (EUS) injection of Onyx-015 with intravenous gemcitabine in unresectable pancreatic carcinoma. American Society of Clinical Oncology Annual Meeting, (2000).
  • ISHIKAWA 0, OHIGASHI H, IMAOKA S etal.: Is the long-term survival rate improved by preoperative irradiation prior to Whipple's procedure for adenocarcinoma of the pancreatic head? Arch. Surg. (1994) 129(10):1075–1080.
  • COIA L, HOFFMAN J, SCHER R et al.: Preoperative chemoradiation for adenocarcinoma of the pancreas and duodenum. Int. j Radiat. Oncol. Biol. Phys. (1994) 30(1):161–167.
  • STALEY CA, LEE JE, CLEARY KR et al.: Preoperative chemoradiation, pancreaticoduodenectomy, and intraoperative radiation therapy for adenocarcinoma of the pancreatic head. Am. Surg. (1996) 171(1):118–124; discussion 124–125.
  • SPITZ FR, ABBRUZZESE JL, LEE JE et al.: Preoperative and postoperative chemoradiation strategies in patients treated with pancreaticoduodenectomy for adenocarcinoma of the pancreas. j. Oncol. (1997) 15(3):928–937.
  • HOFFMAN JP, LIPSITZ S, PISANSKY T et al.: Phase II trial of preoperative radiation therapy and chemotherapy for patients with localized, resectable adenocarcinoma of the pancreas: an Eastern Cooperative Oncology Group Study. I Clin Oncol. (1998) 16(1): 317–323.
  • BRESLIN TM, HESS KR, HARBISON DB etal.: Neoadjuvant chemoradiotherapy for adenocarcinoma of the pancreas: treatment variables and survival duration. Ann. Surg. Oncol. (2001) 8(2):123–132.
  • ••The largest series of patients withadenocarcinomas of the head of the pancreas treated by neoadjuvant chemoradiation from the MD Anderson cancer centre. Note that although the median survival rate of 21 months appears exceptionally good this includes patients with cancers other than pancreatic ductal adenocarcinoma.
  • MEHTA VK, FISHER G, FORD JA et al.: Preoperative chemoradiation for marginally resectable adenocarcinoma of the pancreas. j. Gast-mint-est. Surg. (2001) 5(1):27–35.
  • SNADY H, BRUCKNER H, COOPERMAN A et al.: Survival advantage of combined chemoradiotherapy compared with resection as the initial treatment of patients with regional pancreatic carcinoma. An outcomes trial. Cancer (2000) 89(2):314–327.
  • •A remarkably high median survival rate of32 months with combination neoadjuvant chemoradiotherapy and chemotherapy, probably explained by patient selection and inclusion of patients with tumours other than pancreatic ductal adenocarcinoma.
  • WANEBO HJ, GLICKSMAN AS, VEZERIDIS MP etal.: Preoperative chemotherapy, radiotherapy, and surgical resection of locally advanced pancreatic cancer. Arch. Surg. (2000) 135(1):81–87; discussion 88.
  • WHITER, LEE C, ANSCHER M et al.: Preoperative chemoradiation for patients with locally advanced adenocarcinoma of the pancreas. Ann. Surg. Oncol. (1999) 6(1):38–45.
  • KASTL S, BRUNNER T, HERRMANN 0 et al.: Neoadjuvant radio-chemotherapy in advanced primarily non-resectable carcinomas of the pancreas. Eur. I Surg. Oncol. (2000) 26(6):578–582.
  • PISTERS PW, ABBRUZZESE JL, JANJAN NA et al.: Rapid-fractionation preoperative chemoradiation, pancreaticoduodenectomy, and intraoperative radiation therapy for resectable pancreatic adenocarcinoma. Oncol. (1998) 16(12):3843–3850.
  • BAKKEVOLD KE, ARNESJO B, DAHL 0 et al.: Adjuvant combination chemotherapy (AMF) following radical resection of carcinoma of the pancreas and papilla of Vater--results of a controlled, prospective, randomised multicentre study. Eur. I Cancer (1993) 5:698–703.
  • •A randomised controlled trial of adjuvantcombination chemotherapy showing an increase in long-term survival but not 5-year survival. The toxicity of the regimen limited its intended application.
  • BAUMEL H, HUGUIER M, MANDERSCHEID JC et al.: Results of resection for cancer of the exocrine pancreas: a study from the French Association of Surgery. Br. J. Surg. (1994) 81(1):102–
  • NEOPTOLEMOS JP, DUNN JA, STOCKEN DD etal.: Adjuvant chemoradiotherapy and chemotherapy in resectable pancreatic cancer: a randomised controlled study. Lancet (2001) 358:1576–1585.
  • ••The largest randomised controlled trial ofadjuvant chemotherapy and chemoradiotherapy by far. Clearly showed no benefit for chemoradiotherapy and a possible survival advantage for chemotherapy.
  • JOHNSTONE PA, SINDELAR WF: Patterns of disease recurrence following definitive therapy of adenocarcinoma of the pancreas using surgery and adjuvant radiotherapy:correlations of a clinical trial. Radiat. Omni Biol. Phys. (1993) 27(4):831–834.
  • DI CARLO V, ZERBI A, BALZANO G et al.: Intraoperative and postoperative radiotherapy in pancreatic cancer. Int. Pancreatol. (1997) 21(1):53–58.
  • FARRELL TJ, BARBOT DJ, ROSATO FE: Pancreatic resection combined with intraoperative radiation therapy for pancreatic cancer. Ann. &mg. (1997) 226(1):66–69.
  • HISHINUMA S, OGATA Y, MATSUI J et al.: Results of surgery and adjuvant radiotherapy for pancreatic cancer. Hepatobiliary Pancreat. &mg. (1998) 5(2):143–150.
  • LEE JH, WHITTINGTON R, WILLIAMS NN et al: Outcome of pancreaticoduodenectomy and impact of adjuvant therapy for ampullary carcinomas. Radiat. Omni Biol. Phys. (2000) 47(4)945–953.
  • ALFIERI S, MORGANTI AG, DI GIORGIO A et al.: Improved survival and local control after intraoperative radiation therapy and postoperative radiotherapy: a multivariate analysis of 46 patients undergoing surgery for pancreatic head cancer. Arch. &mg. (2001) 136(3):343–347.
  • ZERBI A, FOSSATI V, PAROLINI D et al: Intraoperative radiation therapy adjuvant to resection in the treatment of pancreatic cancer. Cancer (1994) 73(12):2930–2935.
  • DOBELBOWER RR, MERRICK HVV, KHUDER S et al.: Adjuvant radiation therapy for pancreatic cancer: a 15-year experience. Int. j Radiat. Omni Biol. Phys. (1997) 39(1):31–37.
  • KLINKENBIJL JH, JEEKEL J, SAHMOUD T et al: Adjuvant radiotherapy and 5-fluorouracil after curative resection of cancer of the pancreas and periampullary region: Phase III trial of the EORTC gastrointestinal tract cancer cooperative group. Ann. &mg. (1999) 230(6):776–782; discussion 782–784.
  • •A large randomised controlled trial ofadjuvant chemoradiotherapy (without follow-on chemotherapy) showing no survival benefit. Arguably underpowered.
  • MEHTA VK, FISHER GA, FORD JM et al.: Adjuvant radiotherapy and concomitant 5-fluorouracil by protracted venous infusion for resected pancreatic cancer. Int. j Radiat. Omni Biol. Phys. (2000) 48(5):1483–1487.
  • OZAKI H, KINOSHITA T, KOSUGE T et al.: Long-term survival after multimodality treatment for resectable pancreatic cancer. Intl Pancreatol (2000) 27(3):217–224.
  • LINK KH, FORMENTINI A, GANSAUGE F etal.: Regional celiac artery infusion as adjuvant treatment after pancreatic cancer resection. Digestion (1997) 58(6):529–532.
  • LINK K, GANSAUGEF, PILLASCH J: Regional treatment of advanced nonresectable and of resected pancreatic cancer via celiac axis infusion. First results of a single instituion study. Dig. &mg. (1994) 11:414–419.
  • BEGER HG, GANSAUGE F, BUCHLER MW et al.: Intraarterial adjuvant chemotherapy after pancreaticoduodenectomy for pancreatic cancer: significant reduction in occurrence of liver metastasis. World J. &mg. (1999) 23(9):946–949.
  • KALSER MH, ELLENBERG SS: Pancreatic cancer. Adjuvant combined radiation and chemotherapy following curative resection. Arch. &mg. (1985) 120(8):899–903.
  • •A large randomised controlled trial ofadjuvant chemoradiotherapy (without follow-on chemotherapy) showing no survival benefit. Arguably underpowered.
  • DOUGLASS HO, JR.: Further evidence of effective adjuvant combined radiation and chemotherapy following curative resection of pancreatic cancer. GastrointestinalTumor Study Group. Cancer (1987) 59(12):2006–2010.
  • ••Follow-up paper of the GITSG adjuvanttrial. A further 30 patients registered to the combination adjuvant regimen with similar survival results.
  • CONLON KC, KLIMSTRA DS, BRENNAN MF: Long-term survival after curative resection for pancreatic ductal adenocarcinoma. Clinicopathologic analysis of 5-year survivors. Ann. &mg. (1996) 223(3):273–279.
  • NEOPTOLEMOS JP, THE UK PANCREATIC CANCER GROUP: Adjuvant radiotherapy and follow-on chemotherapy in patients with pancreatic cancer: Results of the UK Pancreatic Cancer study (UKPACA-1). CI Cancer (1998) 2(3):235–245.
  • ABRAMS RA, GROCHOW LB, CHAKRAVARTHY A etal.: Intensified adjuvant therapy for pancreatic and periampullary adenocarcinoma: survival results and observations regarding patterns of failure, radiotherapy dose and CA19-9 levels. Int. J. Radiat. Oncol. Biol. Phys. (1999) 44(5):1039–1046.
  • PAULINO AC: Resected pancreatic cancer treated with adjuvant radiotherapy with or without 5-fluorouracil: treatment results and patterns of failure. Am. J OM. Omni (1999) 22(5):489–494.
  • ANDRE T, BALOSSO J, LOUVET C et al: Combined radiotherapy and chemotherapy (cisplatin and 5-fluorouracil) as palliative treatment for localized unresectable or adjuvant treatment for resected pancreatic adenocarcinoma: results of a feasibility study. Int. I Radiat. Oncol. Biol. Phys. (2000) 46(4):903–1011.
  • NUKUI Y, PICOZZI VJ, TRAVERSO LW: Interferon-based adjuvant chemoradiation therapy improves survival after pancreaticoduodenectomy for pancreatic adenocarcinoma. Am. I &mg. (2000) 179(5):367–371.
  • •The use of interferon-a as part of a combination chemotherapy regimen therapy following chemoradiotherapy is reported to produce a uniquely high survival rate of 84 months at 2 years. The series is small (only 17 patients) but is causing much interest. Watch this space.
  • LEVI F, ZIDANI R, MISSET JL: Randomised multicentre trial of chronotherapy with oxaliplatin, fluorouracil, and folinic acid in metastatic colorectal cancer. International Organization for Cancer Chronotherapy. Lancet (1997) 350(9079):681–686.

Websites

  • http://cancertrials.nci.nih.gov/ Ongoing clinical trials in cancer therapy.

Reprints and Corporate Permissions

Please note: Selecting permissions does not provide access to the full text of the article, please see our help page How do I view content?

To request a reprint or corporate permissions for this article, please click on the relevant link below:

Order Reprints Request Corporate Permissions

Academic Permissions

Please note: Selecting permissions does not provide access to the full text of the article, please see our help page How do I view content?

Obtain permissions instantly via Rightslink by clicking on the button below:

Request Academic Permissions

If you are unable to obtain permissions via Rightslink, please complete and submit this Permissions form. For more information, please visit our Permissions help page.

Related research

People also read lists articles that other readers of this article have read.

Recommended articles lists articles that we recommend and is powered by our AI driven recommendation engine.

Cited by lists all citing articles based on Crossref citations.
Articles with the Crossref icon will open in a new tab.