Abstract
Over the past 20 years the administration of cytokines has emerged as an important fourth modality for the treatment of human cancer. Advances in the field of therapy of gastrointestinal tumors have become a major focus of current research, given the lack of progress of conventional antineoplastic therapy in most of these tumors. Among the heterogeneous group of gastrointestinal malignancies, novel therapeutic strategies have been employed for each individual tumor type, and cytokines (interferon-a) have gained an established role in the treatment of advanced carcinoid tumors. Although our understanding of the mechanisms of biological response modification is still limited, further improvement in the management of gastrointestinal malignancies can be expected from multimodality therapy regimens employing cytokines in combination with other biological response modifiers, chemotherapeutic agents, active-specific immunotherapy, and immunotoxin- and radionuclide-conjugated monoclonal antibodies. A wide range of clinical and preclinical studies have been conducted in colorectal carcinoma; however, potential therapeutic benefit of cytokine-based biotherapy has not been fully defined. Therefore, large-scale, i.e., multicenter, studies are required to quantify the potential therapeutic effects of cytokines in gastrointestinal tumors.
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Abbreviations
- FA:
-
folinicacid
- 5-FU:
-
5-fluorouracil
- GI:
-
gastrointestinal
- HCC:
-
hepatocellular carcinoma
- IFN:
-
interferon
- IL:
-
interleukin
- LAK cells:
-
lymphokineactivated killer cells
- TNF:
-
tumor necrosis factor
References
Abbruzzese JL, Levin B, Ajani JA, Faintuch JS, et al (1990) A phase 11 trial of recombinant human interferon-gamma and recombinant tumor necrosis factor in patients with advanced gastrointestinal malignancies: results of a trial terminated by excessive toxicity. J Biol Response Modif 9:522–527
Ajani JA, Rios AA, Ende K, et al (1989) Phase I and II studies of the combination of recombinant human interferon-gamma and 5-fluouracil in patients with advanced colorectal carcinoma. J Biol Response Modif 8:140–146
Arinaga S, Karimini N, Takamuka K, Nanbara S, Akiyoshi T (1992) Correlation of eosinophilia with clinical response in patients with advanced carcinoma treated with low-dose recombinant interleukin-2 and mitomycin-C. Cancer Immunol Immunother 35:246–250
Arinaga S, Karimine N, Takamuka K, Nanbara S, Akiyoshi T (1992) Enhanced induction of LAK activity after lentinan administration in patients with gastric carcinoma. Int J Immunopharmacol 14:535–539
Atzpodien J, Korfer A, Evers P, Franks CR, Knüver-Hopf J, Lopez-Hänninen E, Fischer M, Mohr H, Dallmann I, Hadam M, Poliwoda H, Kirchner H (1990) Low-dose subcutaneous recombinant interleukin-2 in advanced human malignancy: a phase II outpatient study. Mol Biother 2:18–26
Atzpodien J, Korfer A, Franks CR, Poliwoda H, Kirchner H (1990) Home therapy with recombinant interleukin-2 and interferon-a2b in advanced human malignancies. Lancet 335:1509–1512
Atzpodien J, Kirchner H, Körfer A, Menzel T, Schomburg A, Poliwoda H (1994) Treatment of metastatic colorectal cancer patients with 5-fluouracil in combination with recombinant subcutaneous human interleukin-2 and interferon-α. Oncology 51:273–275
Biesma B, Willemse PHB, Mulder NH, Verschueren RCJ, Kema IP, de Bruijn HWA, Postmus PE, Sleijfer DT, de Vries EGE (1992) Recombinant interferon-alpha 2b in patients with metastatic apudomas: effect on tumours and tumour markers. Br J Cancer 66:850–855
Blottiere HM, Douillard JY, Koporowski H, Steplewski Z (1990) Humoral and cellular responses of colorectal cancer patients treated with monoclonal antibodies and interferon-gamma. Cancer Immunol Immunother 32:29–37
Brown T, Tangen C, Fleming T, Macdonald J (1993) A phase II trial of taxol and granulocyte colony stimulating factor (G-CSF) in patients with adenocarcinoma of the pancreas. Proc ASCO 12:200
Brunetti I, Falcone A, Giannessi P, et al (1991) Double 5-fluorouracil modulation with folinic acid and alfa-2b interferon in metastatic colorectal carcinoma patients. Proc AACR 32:92
Bukowski RM, Inoshita G, Yalavarthi P, Murthy S, Gibson V, Budd GT, Sergi JS, Bauer MS, Prestifilippo J (1992) A phase I trial of 5-fluorouracil, folinic acid, and alpha-2a-interferon in patients with metastatic colorectal carcinoma. Cancer 69:889–892
Cascinu S, Fedeli A, Fedeli SL, Catalano G, Luzi S (1992) Double biochemical modulation of 5-fluorouracil by leucovorin and cyclic low dose interferon-alfa-2b in advanced colorectal cancer. Ann Oncol 3:489–491
Chou T, Chang AE, Shu S (1988) Generation of therapeutic T lymphocytes from tumor-bearing mice by in vitro sensitization. J Immunol 140:2453–2461
Chu E, Zinn S, Allegra C (1991) Translation regulation of thymidilate synthase in response to 5-fluorouracil and gamma-interferon in a human colon cancer cell line. Proc AACR 32:489–491
Creutzfeldt W, Bartsch HH, Jacubaschke U, Stöckmann F (1991) Treatment of gastrointestinal endocrine tumors with interferon-α and octreotide. Acta Oncol 30:529–535
Crown J, Jakubowski A, Kemeny N, Gordon M, et al (1991) A phase I trial of recombinant interleukin-1b alone and in combination with myelosuppressive doses of 5-fluorouracil in patients with gastrointestinal cancer. Blood 78:1420–1427
Derderian P, Pazdur R, Ajani J, et al (1991) Phase II study of 5-fluorouracil and recombinant interferon-alpha-2a in the treatment of advanced pancreatic carcinoma. Proc AACR 10:147
DeVita VT, Hellmann S, Rosenberg SA (eds) (1991) Biologic therapy of cancer. Lippincott, Philadelphia
Diaz-Rubio E, Jimeno J, Camps C, Aranda E, Massati B, Blanco E, Anton A, Lizon J (1992) Treatment of advanced colorectal cancer with recombinant alpha-interferon and fluorouracil. Cancer Invest 10:259–264
DiBartolomeo M, Zilembo N, Castellani R, Tinessa V, Bajetta E (1991) Interferon-alpha-2a in carcinoid and other neuroendocrine tumors. Proc AACR 32:312
Dirix JY, Prove A, Fierens H, VanOosterom AT (1991) Alpha-interferon treatment of metastatic carcinoid tumors. Proc AACR 32:312
Douillard JY, Leborgne J, Danielou JY, et al (1991) Phase II trial of 5-fluorouracil and recombinant interferon-alpha in metastatic, previously untreated colorectal cancer. Proc ASCO 10:139
Elias L, Crissman HA (1988) Interferon effects on the adenocarcinoma 38 and HL-60 cell lines. Antiproliferative responses and synergistic interactions with halogenated pyrimidine antimetabolites. Cancer Res 48:4868–4873
Elias L, Sandoval JM (1989) Interferon effects upon fluorouracil metabolism by HL-60 cells. Biochem Biophys Res Commun 163:864–867
Findlay M, Hill A, Cunningham D, Norman A, Nicolson M, Ford H, Husband J, Evans C, Carter R (1994) Protraced venous infusion 5-fluorouracil and interferon-a in advanced and refractory colorectal cancer. Ann Oncol 5:239–243
Gabrilove J, Jakubowski A, Crown J, et al (1991) A phase I trial of recombinant human interleukin-1 beta alone and in combination with myelosuppressive doses of 5-fluorouracil in patients with gastrointestinal cancer. Ann Hematol 6:99
Gandolfi L, Solmi L, Pizza CG, et al (1989) Intratumoral echo-guided injection of interleukin-2 and LAK cells in hepatocellular carcinoma. Hepatogastroenterology 36:352–356
Gomez J, Pazdur R, Ajani J, et al (1991) Phase II study of 5-fluorouracil and recombinant alpha-2a-interferon in the treatment of advanced gastric carcinoma. Proc ASCO 10:147
Hamblin TJ, Inzani V, Sadullah S, et al (1989) A phase II trial of recombinant interleukin-2 and 5-fluorouracil in patients with metastatic colorectal cancer. Cancer Treat Rev 16:163–167
Hansen R, Schurtz M, Vukelich M, Blake D, Anderson T (1991) A phase II study of 5-fluorouracil infusion, interferon-alpha, and dipyridamole in advanced colorectal cancer. Proc ASCO 10:154
Hansmann E, Grnntjens-Prinsen G, Bremer K, Linnemann G (1991) Additional modulation of 5-fluorouracil by interferon-alpha-2b in advanced colorectal cancer refractory to 5-FU and folinic acid. Proc AACR 32:93
Hayakawa K, Fukushima T, Seito D, Asakura Y, Yamanaka Y, Morita T, Sasaki M, Konn M, Ono K (1989) Continuous arterial infusion therapy of recombinant interleukin-2 and cyclophosphamide in liver metastasis. Gan To Kagaku Ryoho 16:2842–2844
Hiddemann W, Ruelfs C, Ottensmeier C, Ruckle H, Musch E, Koch O, van de Loo J (1992) Interleukin-2 followed by 5-fluorouracil and folinic acid in refractory colorectal cancer — results of a phase II study. Semin Oncol 19:225–227
Huberman M, McLay E, Atkins M, Goldsweig H, Bonanno D, Layton M, Tessitore J (1991) Phase II trial of 5-fluorouracil and recombinant interferon-alpha-2a in advanced colorectal cancer. Proc ASCO 10:153
Iaffaioli RV, Frasci G, Facchini G, et al (1991) Neoadjuvant immunotherapy in locally advanced gastric cancer. Proc AACR 32:77
Israel L, Boaziz C, Moliard M, Morere JF, Breau JL (1991) Phase II study of interleukin-2 in 18 patients with advanced gastrointestinal tract cancers. Proc ASCO 10:139
Jäger-Arand E, Bernhard H, Klein O, Wächter B, Dippold W, Meyer z Büschenfelde KH, Knuth A (1993) Combination 5-fluorouracil (FU), folinic acid (FA) and α-interferon 2b (IFN) in advanced gastric cancer. Proc ASCO 12:192
Jaiyesimi I, Pazdur R, Patt YZ, et al (1991) Phase II study of recombinant inteferon-alpha-2a and continuous infusion 5-fluorouracil in metastatic colorectal carcinoma. Proc ASCO 10:147
Kalofonos HP, Gogos H, Vasiliou V, Karatza C (1991) Interferon alpha and cyproterone acetate in the treatment of primary hepatocellular carcinoma. Proc AACR 32:226
Kawata A, Uchino J, Une Y, et al (1991) Early postoperative chemoimmunotherapy with adriamycin, rIL-2 and spleen derived LAK cells for hepatocellular carcinoma patients. Proc AACR 32:251
Kelsen D, Lovett D, Wong J, et al (1992) Interferon-alpha-2a and fluorouracil in the treatment of patients with advanced esophageal cancer. J Clin Oncol 10:269–274
Kemeny N, Younes A, Seiter K (1992) Interferon-alpha-2a and 5-fluorouracil for the advanced colorectal cacinoma: the Memorial Sloan-Kettering experience. Semin Oncol 19:171–175
Knuth A, Bernhard H, Klein O, Meyer z Büschenfelde KH (1992) Combination of 5-fluorouracil, folinic acid, and interferon-alpha-2a: an active regimen in advanced pancreatic cancer. Semin Oncol 19:211–214
Köhne-Wömper CH, Schmoll HJ, Hiddemann W, et al (1992) 5-Fluorouracil, folinic acid, alpha-2b-interferon in advanced colorectal cancer. Ann Oncol 1:195
Komatsu T, Ymauchi K, Furukawa T, Obata H (1990) Transcatheter arterial injection of autologous lymphokine-activated killer cells into patients with liver cancers. J Clin Immunol 10:167
Kreuser ED, Hilgenfeld RU, Matthias M, Hoksch B, Oldenkott B, Porzsolt F, Disel W (1992) A phase II trial of interferon-alpha-2b with folinic acid and 5-fluorouracil administered by 4 hour infusion in metastatic colorectal cancer. Semin Oncol 19:57–62
Labianca R, Pancera G, Tedeski L, Dallavalle G, Luporini G (1992) High dose alpha 2b-interferon and folinic acid in the modulation of 5-fluorouracil. A phase II study in advanced colorectal cancer with evidence of an unfavorable cost/benefit ratio. Tumori 78:32–34
Lee KH, Lee JS, Suh C, Lee YS, Min YI, Ahu SH, Park UH, Kim SK (1992) Combination of 5-fluorouracil and recombinant alpha-2b-interferon in advanced gastric cancer. Am J Clin Oncol 15:141–145
Lotz JP, Grange JD, Hannoun L, et al (1991) Treatment of unresectable hepatocellular carcinoma with alpha-2b interferon and doxorubicin. Proc AACR 32:73
Lovett D, Kelsen D, Heelan R (1990) 5-Fluorouracil and alpha-interferon in the treatment of esophageal carcinoma. Proc ASCO 9:121
Matheson DS, Green BJ, Friedman SJ, Hoar DI (1988) Studies on the mechanism of activation of human natural killer function by interferon. Cell Immunol 111:118–125
Mattioli R, Manocchi P, Pilone A, et al (1991) Mitomycin + 5-fluorouracil + folinic acid in association with alpha-2b-interferon in advanced colorectal cancer. Proc AACR 32:92
Merrouche Y, Negrier S, Rebattu P, et al (1991) A phase II study of interleukin-2 following high dose BCNU and autologous bone marrow transplantation in the treatment of metastatic gastric cancer. Proc ASCO 10:161
Mittelman A, Savona S, Gafney E, et al (1989) Treatment of patients with advanced cancer using multiple long-term cultured lymphokine-activated killer cell infusions and recombinant human interleukin-2. J Bio Response Modif 8:468–478
Modiano M, Taylor C, Brooks R, Wiggins C, Power J, Alberts D (1993) Etoposide (E), leucovorin (L), 5-fluorouracil (F), and interferon-a2a (I) (ELFI) is an active treatment for high-risk or advanced pancreatic or gastric adenocarcinoma. Proc ASCO 12:203
Monden T, Morimoto H, Shimano T, et al (1992) Use of fibrinogen to enhance the antitumor effects of OK-432. A new approach to immunotherapy for colorectal carcinoma. Cancer 69:636–642
Moertel CG (1978) Chemotherapy of gastrointestinal cancer. New Engl J Med 299:1049–1052
Nio Y, Ohgaki K, Tsuchitani T, et al (1989) Oral administration of OK-432: its immunomodulatory effects on patients with gastrointestinal cancers. Nippon Gan Chiryo Gakkai Shi 24:1607–1615
Nobile MT, Sobrero A, Guglielmi A, et al (1991) Five-fluorouracil and leucovorin and interferon-alpha-2b in advanced colorectal cancer. Proc AACR 32:89
Öberg K, Erikson B (1991) The role of interferons in the management of carcinoid tumours. Br J Haematol 79:74–77
O'Connell MJ, Ritts RA, Moertel CG, Schutt AJ, Sherwin SA (1989) Recombinant interferon-gamma lacks activity against metastatic colorectal cancer. Cancer 63:1998–2004
Onodera H, Somers SS, Guillou PJ (1990) Paradoxical effects of 5-FU/folinic acid on lymphokine activated killer (LAK) cell induction in patients with colorectal cancer. Br J Cancer 62:1042–1046
Order SE, Stillwagon GB, Klein JL (1985) Idoine-131 antiferritin, a new treatment modality in hepatoma: a Radiation Therapy Oncology Group Study. J Clin Oncol 3:1573–1582
Patt Y, Noonan C, Pazdur R, et al (1991) Phase II trial of 5-fluorouracil and recombinant interferon-alpha in hepatocellular carcinoma. Proc ASCO 10:144
Patt YZ, Yoffe B, Charnsangavej C, Pazdur R, Fischer H, Cleary K, Roh M, Smith R, Noonan CA, Levin B (1993) Low serum alpha-fetoprotein level in patients with hepatocellular carcinoma as a predictor of response to 5-FU and interferon-alpha-2b. Cancer 72:2574–2582
Pazdur R, Ajani JA, Winn R, Bearden J, Belt RJ, Pilat S, Levin B (1992) A phase II trial of 5-fluorouracil and recombinant interferon-alpha in previously untreated metastatic gastric cancer. Cancer 69:878–882
Pazdur R, Moore DF, Bready B (1992) Modulation of 5-fluorouracil with recombinant alpha-interferon: M.D. Anderson clinical trial. Semin Oncol 19:176–179
Piedbois P, Gimonet JF, Feuilhade F, et al (1991) 5-Fluorouracil, folinic acid and alpha-2a-interferon combination in advanced gastrointestinal cancer. Proc ASCO 10:141
Preiss J (1992) 5-fluorouracil plus interferon-alpha2a and folinic acid in regional and systemic therapy in colorectal cancer. Semin Oncol 19:220–224
Punt CJA, Burghouts JTM, Croles JJ, vanLiessum PA, deMulder PHM, Kamm Y (1993) Continous infusion of high-dose 5-fluorouracil in combination with leucovorin and recombinant interferon-alpha-2b in patients with advanced colorectal cancer. Cancer 72:2107–2111
Reid I, Lundy J, Monson JRT, et al (1992) Heteroconjugated antibodies enhance lymphocyte-mediated tumour lysis in vitro and in vivo. Br J Surg 79:628–632
Reiter Z, Ozes ON, Blatt LM, Taylor MW (1992) A dual anti-tumor effect of a combination of interferon-α or interleukin-2 and 5-fluorouracil on natural killer cell-mediated cytotoxicity. Clin Immunol Immunopathol 62:103–111
Rosenberg SA, Lotze MT, Muul LM, Chang AE, Avis FP, Leitman S, Linehan WM, Robertson CN, Lee RE, Rubin JT, Seipp CA, Simpson CG, White DE (1987) A progress report on the treatment of 157 patients with advanced cancer using lymphokine-activated killer cells and interleukin-2 or high-dose interleukin-2 alone. NEJM 316:889–897
Rosenberg SA, Lotze MT, Yang JC, Linehan WM, Seipp C, Calabro S, Steinberg S, White DE (1989) Combination therapy with interleukin-2 and alpha-interferon for the treatment of patients with advanced cancer. J Clin Oncol 7:1863–1874
Rustum YM (1991) Rational basis for the metabolic modulation of 5-fluorouracil by leucovorin and interferon-alpha. Br J Haematol 19:52–55
Saleh MN, Khazaeli MB, Grizzle WE, Wheeler RH, Lawson S, Liu T, Russel C, Meredith R, Schlom J, LoBuglio AF (1993) A phase I trial of murine monoclonal antibody D612 in patients with metastatic gastrointestinal cancer. Cancer Res 53:4555–4562
Schmiegel WH, Bützow GH, Lanwieler T (1988) Biological response modifier in pancreatic cancer: clinical phase one trial with recombinant human tumor necrosis factor. Digestion 40:114
Schmoll HJ, Köhne-Wömper CH, Hiddemann W, Knipp H, Wilke H, Bodenstein H, Harstrick A, Hill H (1992) Interferon-alpha2b, 5-fluorouracil, and folinic acid combination therapy in advanced colorectal cancer: preliminary results of a phase I/II trial. Semin Oncol 19:191–196
Schöber C, Schmoll E, Schmoll HJ, Poliwoda H, Schuppert F, Stahl M, Bokemeyer C, Wilke H, Weiss J (1992) Antitumor effect and symptomatic control with interferon-alpha2b in patients with endocrine active tumors. Eur J Cancer 28:1664–1666
Schoof DD, Gramolini BA, Davidson DL, Eberlein TJ, et al (1988) Adoptive immunotherapy of human cancer using low-dose recombinant interleukin-2 and lymphokine-activated killer cells. Cancer Res 48:5007–5010
Schüller J, Czejka M, Miksche M, Fogl U, Jäger W (1991) Influence of interferon-alpha2b with or without leucovorin on pharmacokinetics of 5-fluorouracil. Semin Oncol 2:93–97
Sobrero A, Nobile MT, Gulglielmi A, Mori A, Schele C, Bolli E, Tixi L, Gallo L, Parodi GE, Bruzzi P (1992) Phase II study of 5-fluorouracil plus folinic acid and interferon-alpha2b in advanced colorectal cancer. Eur J Cancer 28:850852
Sporn JR, Buzaid A, Slater D, Greenberg BR (1993) Treatment of advanced pancreatic cancer with cisplatin, 5-FU, leucovorin, and interferon α-2b. Proc ASCO 12:207
Steger GG, Mader RM, Djavanmard MP, Gnant MFX, Locker G, Marosi C, Rainer H, Jakesz R (1994) Double modulation of 5-fluorouracil by high-dose leucovorin and interferon a2b in advanced colorectal caner: a phase I and a phase II study of weekly administration. J Cancer Res Clin Oncol 120:314–318
Steis RG, Urba WJ, VanderMolen LA, et al (1990) Intraperitoneal lymphokine-activated killer cell and interleukin-2 therapy for malignancies limited to the peritoneal cavity. J Clin Oncol 8:1618–1629
Stolfi RL, Martin DS (1985) Modulation of chemotherapeutic drug activity with polyribonucleotides or with interferon. J Biol Response Modif 4:634–639
Strack M, Wadler S, Lyver A (1990) Phase II trial of fluorouracil and recombinant alpha-2a-interferon in patients with advanced carcinoma of the esophageus. Proc ASCO 9:119
Takagi K, Fukushima Y, Takano M, et al (1992) Exogenous and endogenous TNF therapy for advanced colorectal cancer. Ann Oncol 1:167
TakekoshiH, Yoshida K, Moringa S (1992) Immunochemotherapy of carcinomtous peritonitis and pleuritis. Gan To Kagaku Ryoho 19:1466–1469
Taleghani BM, Porowski P, Klink M, Gunzer U (1991) Interleukin-2 and alpha-interferon sc in combination with 5-fluorouracil and folinic acid iv in advanced progressive colorectal cancer. Ann Hematol 6:126
Tang ZY, Liu KD, Bao YM, et al (1990) Radioimmunotherapy in the multimodality treatment of hepatocellular carcinoma with reference to second look resection. Cancer 65:211–215
The Gastrointestinal Tumor Study Group (1990) A prospective trial of recombinant human interferon-alpha-2b in previously untreated patients with hepatocellular carcinoma. Cancer 66:135–139
Tsugita M, Yamauchi K, Komatsu T, Suzuki H, Hanyu F (1990) Induction and clinical utilization of lymphokine-activated killer cells in patients with gastrointestinal tract cancers. J Gastroenterol Hepatol 5:110–115
Ubhi SS, Hollingworth J, Horsburgh T, Veitch PS, Franks CR, Bell PR (1992) Evaluation of the safety of recombinant interleukin-2 and recombinant interleukin-2 plus 5-fluorouracil in the adjuvant treatment of gastric carcinoma patients. Anticancer Res 12:749–752
VonHoff DD, Fleming TR, MacDonald JS, et al (1990) Phase II evaluation of recombinant gamma-interferon in patients with advanced pancreatic carcinoma. J Biol Response Modif 9:584–587
Wadler S, Wiernik PH (1990) Clinical update on the role of fluorouracil and recombinant interferon-alpha-2a in the treatment of colorectal carcinoma. Semin Oncol 17:16–21
Wadler S, Schwartz EL, Goldman M, et al (1989) Fluorouracil and recombinant alpha-2a-interferon: an active regimen against advanced colorectal carcinoma. J Clin Oncol 7:1769–1775
Wadler S (1991) The role of immunotherapy in colorectal cancer. Semin Oncol 18:27–38
Wadler S, Lembersky B, Atkins M, Kirkwood J, Petrelli N (1991) Phase II trial of fluorouracil and recombinant interferon-alpha-2a in patients with advanced colorectal carcinoma. J Clin Oncol 9:1806–1810
Weh HJ, Platz D, Braumann D, et al (1991) Treatment of metastatic colorectal carcinoma with 5-fluorouracil and interferon-alpha-2b. Proc AACR 32:93
Weiner LM, Steplewski Z, Koprowski H, Herlyn DM (1986) Biologic effects of gamma interferon pre-treatment followed by monoclonal antibody 17–1A administration in patients with gastrointestinal carcinoma. Hybridoma 5:65–77
Weiner LM, Haller DG, Kirkwood J, et al (1991) Phase II trial of repetitive murine monoclonal antibody therapy in pancreatic carcinoma. Proc ASCO 10:161
West WH, Tauer KW, Yannelli JR, Marshall GD, Thurman GB, Oldham RK (1987) Constant-infusion recombinant interleukin-2 in adoptive immunotherapy of advanced cancer. New Engl J Med 316:898–905
Zaniboni A, Marpicati P, Simoncini E, et al (1991) Fluorouracil, high dose folinic acid, low-dose alpha-2b-interferon and dipyridamole in the treatment of advanced colorectal cancer. J Chemother 3:180–182
Ziegler LD, Palazzolo P, Cunningham J, Janus M, Itch K, Hayakawa K, Murray JL (1992) Phase I trial of murine monoclonal antibody L6 in combination with subcutaneous interleukin-2 in patients with advanced carcinoma of the breast, colorectum, and lung. J Clin Oncol 10:1470–1478
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Buer, J., Kirchner, H., Schomburg, A. et al. Cytokine-based biotherapy of gastrointestinal tumors. Clin Investig 72, 526–534 (1994). https://doi.org/10.1007/BF00207483
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DOI: https://doi.org/10.1007/BF00207483