Novel treatments and therapies in development for pancreatic cancer

Expert Opinion on Investigational Drugs

Volumn 11, Issue 6, 2002, Pages 769-786

  Günzburg, Walter H ^a   Löhr, Matthias ^a   Salmons, Brian ^a  

^a UNIVERSITY OF VETERINARY MEDICINE   (Austria)

Author keywords

Cell therapy; Chemotherapy; Combination therapies; Gene therapy; Immunotherapy; Pancreatic cancer; Radiation therapy

Indexed keywords

ALTIMA; ANTINEOPLASTIC AGENT; CARBOHYDRATE DERIVATIVE; CEA CIDE; DIETHYLNORSPERMINE; DNA TOPOISOMERASE INHIBITOR; DOCETAXEL; EDRECOLOMAB; EXATECAN; FLUOROURACIL; GAMMA INTERFERON; GBC 590; GEMCITABINE; GOSERELIN; GYRASE INHIBITOR; IRINOTECAN; IROFULVEN; MARIMASTAT; MONOCLONAL ANTIBODY; OCTREOTIDE; PANCREAS ENZYME; PEMETREXED; POLYAMINE DERIVATIVE; RITUXIMAB; RUBITECAN; SB 408075; TAMOXIFEN; TOPOTECAN; TOXIN; TRASTUZUMAB; TROXACITABINE; UNCLASSIFIED DRUG; UNINDEXED DRUG; ANTINEOPLASTIC ANTIMETABOLITE; DEOXYCYTIDINE; DRUG DERIVATIVE; ENZYME INHIBITOR; HORMONE;

ALOPECIA; ANIMAL EXPERIMENT; ANIMAL MODEL; BONE MARROW SUPPRESSION; CANCER COMBINATION CHEMOTHERAPY; CLINICAL TRIAL; CONTROLLED CLINICAL TRIAL; CONTROLLED STUDY; DIARRHEA; DRUG DESIGN; DRUG MECHANISM; DRUG POTENTIATION; DRUG RESEARCH; FATIGUE; FEVER; GASTROINTESTINAL DISEASE; HAIR LOSS; HUMAN; HYPERBILIRUBINEMIA; LIVER DISEASE; MOUSE; MULTICENTER STUDY; NAUSEA AND VOMITING; NEUTROPENIA; NONHUMAN; PANCREAS CANCER; PHASE 1 CLINICAL TRIAL; PHASE 2 CLINICAL TRIAL; PHASE 3 CLINICAL TRIAL; REVIEW; SURVIVAL TIME; THROMBOCYTOPENIA; TREATMENT OUTCOME; ANIMAL; GENE THERAPY; IMMUNOTHERAPY; PANCREAS TUMOR;

ANIMAL; ANTIBODIES, MONOCLONAL; ANTIMETABOLITES, ANTINEOPLASTIC; ANTINEOPLASTIC AGENTS; DEOXYCYTIDINE; ENZYME INHIBITORS; GENE THERAPY; HORMONES; HUMAN; IMMUNOTHERAPY; PANCREATIC NEOPLASMS; ANIMALS; HUMANS;

EID: 0036016089     PISSN: 13543784     EISSN: None     Source Type: Journal    
DOI: 10.1517/13543784.11.6.769     Document Type: Review

References (141)

1. Estimates of the worldwide incidence of 25 major cancers in 1990
2. Survival of cancer of the pancreas. Bases for new strategies in diagnosis and therapy
3. Resected adenocarcinoma of the pancreas-616 patients: Results, outcomes, and prognostic indicators
4. Cancer Statistics, 1998
5. Standard Kausch-Whipple pancreatoduodenectomy
6. A surgical and pathological based classification of resection of pancreatic cancer: Summary of an international workshop on surgical procedures in pancreatic cancer
7. Treatment of advanced and metastatic pancreatic cancer
8. A Phase II pilot trial of 13-cis retinoic acid and interferon-alpha in patients with advanced pancreatic carcinoma
9. Phase I trial of radiation dose escalation with concurrent weekly full-dose gemcitabine in patients with advanced pancreatic cancer
10. Adjuvant chemoradiotherapy and chemotherapy in resectable pancreatic cancer: A randomised controlled trial
11. Localized adenocarcinoma of the pancreas: The rationale for preoperative chemoradiation
12. Action of 2′,2′-difluorodeoxycytidine and 1-b-D-aribinofuranosylcytosine
13. Modulatory activity of 2′,2′-difluorodeoxycytidine on the phosphorylation and cytotoxicity of arabinosyl nucleosides
14. Evaluation of the antitumour activity of gemcitabine
15. Gemcitabine-induced programmed cell death (apoptosis) of human pancreatic carcinoma is determined by Bcl-2 content
16. 2′,2′-Difluorodeoxycytidine (gemcitabine) induces apoptosis in myeloma cell lines resistant to steroids and 2-chlorodeoxyadenosine (2-CdA)
17. Improvements in survival and clinical benefit with gemcitabine as first-line therapy for patients with advanced pancreas cancer - A randomized trial
18. Gemcitabine-effective palliative therapy for pancreas cancer patients failing 5-FU
19. Gemcitabine and 5-fluorouracil in advanced pancreatic cancer, a GISCAD pahse II study
20. A Phase I-II study of gemciatbine plus continuous infusion 5-fluorouracil in patients with advanced pancreatic cancer
21. The matrix metalloproteinases and their inhibitors in the treatment of pancreatic-cancer
22. Marimastat as first-line therapy for patients with unresectable pancreatic cancer: A randomized trial
23. Polyamine metabolism as target for cancer chemoprevention
24. Polyamines and acetylpolyamines increase the stability and alter the conformation of nucleosome core particles
25. Spermine prevents endonuclease activation and apoptosis in thymocytes
26. Induction of programmed cell death in human breast cancer cells by an unsymmetrically alkylated polyamine analogue
27. Topoisomerase I poisons and suppressors as anticancer drugs
28. Alkyl esters of camptothecin and 9-nitrocamptothecin - Synthesis, in-vitro pharmacokinetics, toxicity, and antitumor-activity
29. CPT-11 converting carboxylesterase and topoisomerase activities in tumour and normal colon and liver tissues
30. Irinotecan plus gemcitabine induces both radiographic and CA 19-9 tumor marker responses in patients with previously untreated advanced pancreatic cancer
31. A Phase I trial of topotecan and gemcitabine administered weekly for 3 consecutive weeks to patients with advanced tumors
32. A study of 9-nitrocamptothecin (RFS-2000) in patients with advanced pancreatic cancer
33. In vitro antitumor activity of 9-nitrocamptothecin as a single agent and in combination with other antitumor drugs
34. A Phase-I and pharmacokinetic (Pk) study of DX-8951F, a novel hexacyclic camptothecin (CPT) analog, on a 30 minute infusion daily for 5 days every 3 weeks schedule
35. Phase-I and pharmacokinetic study of DX-8951F, a novel topoisomerase-I inhibitor, using a 30 minute infusion weekly X-3 every 4 weeks
36. Phase-I and pharmacokinetic study of DX-8951F, a novel topoisomerase-1 inhibitor, using a 30 minute infusion every 3 weeks
37. Phase-I and pharmacokinetic (Pk) study of DX-8951F, a novel camptothecin analog, given as 30-minute infusion daily for 5 days
38. Clinical-applications of the camptothecins
39. DX-8951F, a water-soluble camptothecin analog, exhibits potent antitumor-activity against a human lung-cancer cell-line and its Sn-38-resistant variant
40. Final results of a Phase II study of DX-8951f (Exatecan Mesylate, DX) in advanced pancreatic cancer
41. Antagonism between camptothecin and topoisomerase II-directed chemotherapeutic agents in a human leukemia cell line
42. Sequence effect of irinotecan (CPT-11) and topoisomerase II inhibitors in vivo
43. The new dioxolane, (-)-2′deoxy-3′-oxacytidine (BCH-4556, troxacitabine), has activity against pancreatic human tumor xenografts
44. Troxacitabine (Bch-4556), a nucleoside analog with distinct stereochemical, pharmacological and pharmacokinetic characteristics is tolerable and active in Phase-I studies - The NCI-Cctg experience
45. Ncicctg IND-103 - A Phase-I and pharmacokinetic (Pk) study of the novel L-nucleoside analog troxacitabine (Bch-4556) given every 21 days
46. Phase-I and pharmacokinetic (Pk) study of troxacitabine (B-L-Dioxoran-Cytidine-Bch-4556) on a daily X 5-day every 4-week schedule
47. A Phase I study of GBC-590 in patients with maligancy relapsing or refractory to standard therapy
48. Treatment of advanced pancreatic carcinoma with GBC-590: A Phase II trial
49. Metabolism of antitumor hydroxymethylacylfulvene by rat-liver cytosol
50. Drug uptake and cellular targets of hydroxymethylacylfulvene
51. Detection of MMTV-like LTR and LTR-env gene sequences in human breast cancer
52. Overexpression of p21 (WAF1/CIP1) is an early event in the development of pancreatic intraepithelial neoplasia
53. Efficacy of HMAF (MGI-114) in the MV522 metastatic lung carcinoma xenograft model nonresponsive to transditional anticancer agents
54. Antitumor activity of MGI 114 (6-hydroxymethylacylfulvene, HMAF), a semisynthetic derivative of illudin S, against adult and pediatric human tumor colony-forming units
55. Phase II trial of irofulven (MGI 114) in patients with advanced pancreatic cancer who have progressed on gemcitabine
56. Evaluation of pancreatic proteolytic enzyme treatment of adenocarcinoma of the pancreas, with nutrition and detoxification support
57. Sex steroid receptors and antisteroid agents in the treatment of pancreatic adenocarcinoma
58. Tamoxifan therapy in unresectable adenocarcinoma of the pancreas
59. Tamoxifen therapy in unresectable adenocarcinoma of the pancreas and papilla of Vater
60. Clinical trial of tamoxifan in patients with irresectable pancreatic adenocarcinoma
61. Hormonal treatment of pancreatic carcinoma, a Phase II study of LHRH agonist goserelin plus hydrocortisone
62. LH-RH analogue treatment in adenocarcinoma of the pancreas, a Phase II study
63. Treatment of patients with metastic pancreatic and gastrointestinal tumours with the somatostatin analogue sandostatin, a Phase II study including endocrine effects
64. Low-dose octreotide treatment is not effective in patients with advanced pancreatic cancer
65. Inhibition of growth and metastatic progression of pancreatic carcinoma in hamster after somatostatin receptor subtype 2 (sst2) gene expression and administration of cytotoxic somatostatin analog AN-238
66. Enzyme inhibition, polyglutamation, and the effect of LY231514 (MTA) on purine biosynthesis
67. A Phase I evaluation of multitargeted antifolate (MTA, LY231514), administered every 21 days, utilizing the modified continual reassessment method for dose escalation
68. Phase II study of the multitargeted antifolate LY231514 (ALIMTA, MTA, pemetrexed disodium) in patients with advanced pancreatic cancer
69. Overexpression of the HER-2/neu oncogene in pancreatic adenocarcinoma
70. Superantigen-based immunotherapy: A Phase I trial of PNU-214565, a monclonal antibody-staphylococcal enterotoxin A recombinant fusion protein, in advanced pancreatic and colorectal cancer
71. Phase I study of single, escalating doses of a superantigen-antibody fusion protein (PNU-214565) in patients with advanced colorectal or pancreatic carcinoma
72. Phase II multicenter evaluation of prolonged murine monoclonal antibody 17-1A therapy in pancreatic carcinoma
73. Phase II trial of interferon gamma and monoclonal antibody 17-1A therapy in pancreatic carcinoma
74. Coexpression of epidermal growth factor receptor and ligands in human pancreatic cancer is associated with enhanced tumor aggressiveness
75. The epidermal growth factor receptor as a target for cancer therapy
76. Virulizin(R) - A review of its antineoplastic activity
77. Phase II trial of Virulizin in patients with pancreatic cancer
78. Identification of proliferating dendritic cell precursors in mouse blood
79. Novel allogeneic granulocyte-macrophage colony-stimulating factor-secreting tumor vaccine for pancreatic cancer: A phase I trial of safety and immune activation
80. Trial Watch
81. Cytokine Gene-Modified Cell-Based Cancer Vaccines
82. Ex vivo ras peptide vaccination in patients with advanced pancreatic cancer: Results of a Phase I/II study
83. Therapeutic effect of the gastrin receptor antagonist, CR2093 on gastrointestinal tumour cell growth
84. Regulation of growth of human gastric cancer by gastrin and glycine-extended progastrin
85. Gastrimmune raises antibodies that neutralize amidated and glycine-extended gastrin-17 and inhibit the growth of colon cancer
86. Heat shock protein-peptide complexes as immunotherapy for human cancer
87. Ras oncogenes in human cancer: A review
88. Creation of human tumour cells with defined genetic elements
89. Essential role for oncogenic Ras in tumour maintenance
90. K-ras and p53 gene mutations in pancreatic cancer: Ductal and nonductal tumors progress through different genetic lesions
91. Liposome-mediated in vivo gene transfer of antisense K-ras construct inhibits pancreatic tumor dissemination in the murine peritoneal cavity
92. A combinatorial approach for selectively inducing programmed cell death in human pancreatic cancer cells
93. Antitumor activity of a phosphorothioate antisense oligodeoxynucleotide targeted against C-raf kinase
94. Phase I trial of c-raf antisense oligonucleotide ISIS 5132 (CGP 69846A) by 21-day continuous infusion (CIV) in patients with advanced cancer
95. Phase I trial of the c-Raf-1 antisense oligonucleotide (ODN) ISIS 5132 administered as a 21-day continuous IV infusion in combination with 5-fluorouracil (5-FU) and leucovorin (LV) as a daily x5 IV bolus
96. Amplification of Akt2 in human pancreatic-cancer cells and inhibition of Atk2 expression and tumorigenicity by antisense RNA
97. The dominant negative H-ras mutant, N116Y, suppresses growth of metastatic human pancreatic cancer cells in the liver of nude mice
98. Somatostain analogs for diagnosis and treatment of cancer
99. Gene therapy for pancreatic carcinoma: Local and distant antitumor effects after somatostatin receptor sst2 gene transfer
100. Enhanced pancreatic tumor regression by a combination of adenovirus and retrovirus-mediated delivery of the herpes simplex virus thymidine kinase gene
101. Gene therapy of metastatic pancreas cancer with intraperitoneal injections of concentrated retroviral herpes simplex thymidine kinase vector supernatant and ganciclovir
102. Gene therapy for cancer using tumour-specific prodrug activation
103. In vivo adenoviral-mediated gene transfer in the treatment of pancreatic cancer
104. Induction of protective immunity against syngeneic rat cancer cells by expression of the cytosine deaminase suicide gene
105. The bioactivation of 5-(aziridin-1-yl)-2,4-dinitrobenzamide (CB 1954). I. Purification and properties of a nitroreductase enzyme from Escherichia coli - A potential enzyme for antibody directed enzyme prodrug therapy (ADEPT)
106. Sensitization of colorectal and pancreatic cancer lines to the prodrug 5-aziridin-1-yl-2,4-dinitrobenzamide (CB1954) by retroviral transduction and expression of the E Coli nitroreductase gene
107. Virus directed enzyme prodrug therapy for ovarian and pancreatic cancer using retrovirally delivered E. coli nitroreductase and CB 1954
108. Ifosfamide chemotherapy for pancreatic carcinoma
109. Ifosfamide in advanced pancreatic cancer
110. Ifosfamide chemotherapy ineffective for advanced pancreatic carcinoma
111. Cell-cycle disruptions and apoptosis induced by the cyclophosphamide derivative mafosfamide
112. Induction of apoptosis in murine tumors by cyclophosphamide
113. Necrotic, rather than apoptotic, cell death caused by cytochrome P450 activated ifosfamide
114. Prevalence and clinical significance of combined K-ras mutation and p53 aberration in pancreatic adenocarcinoma
115. 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
116. Adenovirus mediated transfer of wild-type p16INK4 and p53 in pancreatic cancer in vitro and in vivo
117. Treatment based on a combination of the CYP2B1/cyclophosphamide system and p53 delivery enhances tumour regression in human pancreatic cancer
118. Modulation of cyclophosphamide-based cytochrome P450 gene therapy using liver P450 inhibitors
119. Gene therapy for malignant gliomas using replication incompetent retroviral and adenoviral vectors encoding the cytochrome P450 2B1 gene together with cyclophosphamide
120. Direct retroviral delivery of human cytochrome P450 2B6 for gene- directed enzyme prodrug therapy of cancer
121. Encapsulated cells producing retroviral vectors for in vivo gene transfer
122. The p53 tumour suppressor gene
123. p53 function and dysfunction
124. Molecular pathology of pancreatic cancer
125. An adenovirus mutant that replicates selectively in p53-deficient human tumor cells
126. Onyx-015, an E1B gene-attenuated adenovirus, causes tumor-specific cytolysis and antitumoral efficacy that can be augmented by standard chemotherapeutic-agents
127. P53-dependent cell-death apoptosis is required for a productive adenovirus infection
128. Replication of Onyx-015, a potential anticancer adenovirus, is independent of p53 status in tumor-cells
129. Does the antitumor adenovirus ONYX-015/dl1520 selectively target cells defective in the p53 pathway?
130. p14ARF links the tumour suppressors RB and p53
131. ARF promotes MDM2 degradation and stabilizes p53: ARF-INK4a locus deletion impairs both the Rb and p53 tumor suppression pathways
132. Replication-selective viruses for cancer therapy
133. Efficacy of a replication-competent adenovirus (ONYX-015) following intratumoral injection: Intratumoral spread and distribution effects
134. Safety and feasibility of injection with an E1B-55 kDa gene-deleted, replication-selective adenovirus (ONYX-015) into primary carcinomas of the pancreas: A Phase I trial
135. Onyx-015- Clinical data are encouraging
136. A controlled trial of intratumoral ONYX-015, a selectively-replicating adenovirus, in combination with cisplatin and 5-fluorouracil in patients with recurrent head and neck cancer
137. Effective gene therapy for pancreatic cancer by cytokines mediated by restricted replication-competent adenovirus
138. Gemcitabine alone or with cisplatin for the treatment of patients with locally advanced and/or metastatic pancreatic carcinoma: A prospective, randomized Phase III study of the Gruppo Oncologia dell'Italia Meridionale