Subcutaneous interleukin-2 in combination with medroxyprogesterone acetate and antioxidants in advanced cancer responders to previous chemotherapy: Phase II study evaluating clinical, quality of life, and laboratory parameters

Journal of Experimental Therapeutics and Oncology

Volumn 3, Issue 4, 2003, Pages 205-219

  Mantovani, Giovanni ^a   Madeddu, Clelia ^a   Gramignano, Giulia ^a   Lusso, Maria Rita ^a   Mocci, Miria ^a   Massa, Elena ^a   Ferreli, Luca ^a   Astara, Giorgio ^a   Macciò, Antonio ^a   Serpe, Roberto ^a  

^a UNIVERSITY OF CAGLIARI   (Italy)

Author keywords

Antioxidant agents; Clinical outcome; Combined maintenance therapy; Interleukin 2; Medroxyprogesterone acetate; Proinflammatory cytokines

Indexed keywords

ACETYLCYSTEINE; ANTINEOPLASTIC AGENT; ANTIOXIDANT; BIOLOGICAL MARKER; C REACTIVE PROTEIN; CARBOCISTEINE; CYTOKINE; FIBRINOGEN; GLUTATHIONE PEROXIDASE; INTERLEUKIN 1BETA; INTERLEUKIN 2; INTERLEUKIN 6; ISOTRETINOIN; LEPTIN; MEDROXYPROGESTERONE ACETATE; PARACETAMOL; REACTIVE OXYGEN METABOLITE; RECOMBINANT INTERLEUKIN 2; SCAVENGER; SUPEROXIDE DISMUTASE; THIOCTIC ACID; TIOBEC; TUMOR NECROSIS FACTOR ALPHA;

ADULT; ADVANCED CANCER; AGED; APPETITE; ARTICLE; BLOOD; BLOOD CHEMISTRY; BLOOD TOXICITY; BODY MASS; BODY WEIGHT; CANCER CHEMOTHERAPY; CANCER HORMONE THERAPY; CANCER IMMUNOTHERAPY; CANCER RADIOTHERAPY; CANCER STAGING; CANCER SURVIVAL; CLINICAL ARTICLE; CLINICAL TRIAL; COGNITION; DRUG COMBINATION; DRUG RESPONSE; FEMALE; FLU LIKE SYNDROME; FOLLOW UP; FUNCTIONAL ASSESSMENT; HEAD AND NECK CANCER; HUMAN; LUNG CANCER; LYMPHOCYTE COUNT; MAINTENANCE THERAPY; MALE; METABOLISM; METASTASIS; MULTIMODALITY CANCER THERAPY; NEOPLASM; OPEN STUDY; PATHOLOGY; PHASE 2 CLINICAL TRIAL; PRIORITY JOURNAL; QUALITY OF LIFE; SKIN TOXICITY; SURVIVAL RATE; TREATMENT OUTCOME;

ACETYLCYSTEINE; ADULT; AGED; ANTINEOPLASTIC COMBINED CHEMOTHERAPY PROTOCOLS; ANTIOXIDANTS; C-REACTIVE PROTEIN; CYTOKINES; DRUG THERAPY, COMBINATION; FEMALE; FREE RADICAL SCAVENGERS; HUMANS; INTERLEUKIN-2; LEPTIN; LYMPHOCYTE COUNT; MALE; MEDROXYPROGESTERONE 17-ACETATE; MIDDLE AGED; NEOPLASM STAGING; NEOPLASMS; QUALITY OF LIFE; SURVIVAL RATE; THIOCTIC ACID; TREATMENT OUTCOME;

EID: 10744222534     PISSN: 13594117     EISSN: None     Source Type: Journal    
DOI: 10.1046/j.1359-4117.2003.01096.x     Document Type: Article

References (57)

1. Mantovani G, Macciò A, Esu S, et al. Lack of correlation between defective cell-mediated immunity and levels of secreted or circulating cytokines in a study of 90 cancer patients. Int J Oncol 5: 1211-1217, 1994.
2. Lai P, Rabinowich H, Crowley-Nowick PA, Bell MC, Mantovani G, Whiteside TL. Alterations in expression and function of signal-transducing proteins in tumor-associated T and natural killer cells in patients with ovarian carcinoma. Clin Cancer Res 2: 161-173, 1996.
3. Mantovani G, Macciò A, Mura L, et al. Serum values of proinflammatory cytokines inversely correlate with serum leptin levels in patients with advanced stage cancer at different sites. J Mol Med 79: 406-414, 2001.
4. Smith KA. Interleukin-2: inception, impact and implications. Science (Wash. DC) 240: 1169-1176, 1988.
5. Cantrell DA, Smith KA. The interleukin-2 T cell system: a new cell growth model. Science (Wash. DC) 224: 1312-1316, 1984.
6. Diamantstein T. Interleukin-2 and the interleukin-2 receptor complex. In: Rees RC, ed. Biology and Clinical Application of IL 2. Oxford: Oxford University Press 15-22, 1990.
7. Semenzato G, Pizzolo G, Zambello R. The interleukin-2/interleukin-2 receptor system: structural, immunological and clinical features. Int J Clin Lab Res 22: 133-142, 1992.
8. Pavletic Z, Benyunes MC, Thompson JA, Lindgren CG, Massumoto C, Alderson MR, Buckner CD, Fefer A. Induction by interleukin-7 of lymphokine-activated killer activity in lymphocytes from autologous and syngeneic marrow transplant recipients before and after systemic interleukin-2 therapy. Exp Hematol 21: 1371-1378, 1993.
9. Fyfe G, Fisher RI, Rosenberg SA, Sznol M, Parkinson DR, Louie AC. Results of treatment of 255 patients with metastatic renal cell carcinoma who received high-dose recombinant interleukin-2 therapy. J Clin Oncol 13: 688-696, 1995.
10. Lindemann A, Brossart P, Hoffken K, Flasshove M, Voliotis D, Diehl V, Hecker G, Wagner H, Mertelsmann R. Immunomodulatory effects of ultra low dose IL-2 in cancer patients: a phase IB study. Cancer Immunol Immunother 37: 307-315, 1993.
11. Mantovani G, Macciò A, Bianchi A, Curreli L, Ghiani M, Santona MC, Del Giacco GS. Megestrol acetate in neoplastic anorexia/cachexia: clinical evaluation and comparison with cytokine levels in patients with head and neck carcinoma treated with neoadjuvant chemotherapy. Int J Clin Lab Res 25: 135-141, 1995.
12. Mantovani G, Macciò A, Esu S, et al. Medroxyprogesterone acetate reduces the in vitro production of cytokines and serotonin involved in anorexia/cachexia and emesis by peripheral blood mononuclear cells of cancer patients. Eur J Cancer 33: 602-607, 1997.
13. Sies H. Oxidative stress: oxidants and antioxidants. Exp Physiol 82: 291-295, 1997.
14. Packer L, Witt EH, Tritschler HJ. Alpha-lipoic acid as a biological antioxidant. Free Radic Biol Med 19: 227-250, 1995.
15. Brennan M. Uncomplicated starvation versus cancer cachexia. Cancer Res 37: 2359-2364, 1997.
16. Mantovani G, Macciò A, Versace R, et al. Tumor-associated lympho-monocytes from neoplastic effusions are immunologically defective in comparison with patient autologous PBMCs but are capable of releasing high amounts of various cytokines. Int J Cancer 71: 724-731, 1997.
17. Han D, Handelman G, Marcocci L, et al. Lipoic acid increases de novo synthesis of cellular glutathione by improving cysteine utilization. Biofactors 6: 321-338, 1997.
18. Behr J, Maier K, Degenkolb B, Krombach F, Vogelmeier C. Antioxidative and clinical effects of high-dose N-acetylcysteine in fibrosing alveolitis. Adjunctive therapy to maintenance immunosuppression. Am J Respir Crit Care Med 156: 1897-1901, 1997.
19. Mantovani G, Macciò A, Lai P, et al. Results of a dose-intense phase I study of a combination chemotherapy regimen with cisplatin (CDDP) and epidoxorubicin (EPI) including medroxyprogesterone acetate (MPA) and recombinant interleukin 2 (rIL-2) in patients with inoperable primary lung cancer. J Immunother 23: 267-274, 2000.
20. Mantovani G, Macciò A, Mulas C, et al. Dose-intense phase II study of weekly cisplatin and epidoxorubicin plus medroxyprogesterone acetate and recombinant interleukin 2 in stage IIIB-IV non-small-cell lung cancer. Oncol Rep 9: 661-670, 2002.
21. Mantovani G, Macciò A, Madeddu C, et al. Immunotherapy (recombinant interleukin 2), hormone therapy (medroxyprogesterone acetate) and antioxidant agents as combined maintenance treatment of responders to previous chemotherapy. Int J Oncol 18: 383-391, 2001.
22. Mantovani G, Macciò A, Madeddu C, et al. Phase II study of subcutaneously administered interleukin-2 in combination with medroxyprogesterone acetate and antioxidant agents as maintenance treatment in advanced cancer responders to previous chemotherapy. Oncol Rep 9: 887-896, 2002.
23. Herberman RB. Design of clinical trials with biological response modifiers. Cancer Treat Rep 69: 1161-1164, 1985.
24. Fayers P, Aaronson N, Bjordal K: EORTC QLQ-C30 Scoring Manual, 2nd edition. EORTC Quality of Life Study Group. Brussels, 1999.
25. Aaronson NK, Ahmedzai S, Bergman B, et al. The European Organization for Research and Treatment of Cancer QLQ-C30: a quality-of-life instrument for use in international clinical trials in oncology. J Natl Cancer Inst 85: 365-376, 1993.
26. Mantovani G, Macciò A, Mura L, et al. Serum levels of leptin and proinflammatory cytokines in patients with advanced-stage cancer at different sites. J Mol Med 78: 554-561, 2000.
27. Alberti A, Bolognini L, Macciantelli D, Caratelli M. The radical cation of N,N-diethyl-para-phenylendiamine: a possible indicator of oxidative stress in biological samples. Res Chem Intermed 26: 253-267, 2000.
28. Dal Negro RW, Visconti M, Micheletto C, Pomari C, Squaranti M, Turati C, Trevisan F, Tognella S. Valori di Normalità e Ripetibilità delle Misure di Stress Ossidativo determinate mediante FORM System. GIMT (in press).
29. Mantovani G, Macciò A, Madeddu C, et al. Quantitative evaluation of oxidative stress, chronic inflammatory indexes and leptin in cancer patients: correlation with stage and performance status. Int J Cancer 98: 84-91, 2002.
30. Recchia F, De Filippis S, Rosselli M, Saggio G, Cesta A, Fumagalli L, Rea S. Phase IB study of subcutaneously administered interleukin 2 in combination with 13-cis retinoic acid as maintenance therapy in advanced cancer. Clin Cancer Res 7: 1251-1257, 2001.
31. Mantovani G, Macciò A, Madeddu C, et al. The impact of different antioxidant agents alone or in combination on reactive oxygen species, antioxidant enzymes and cytokines in a series of advanced cancer patients at different sites: correlation with disease progression. Free Radic Res 37: 213-223, 2003.
32. Mantovani G, Macciò A, Madeddu C, et al. Reactive oxygen species, antioxidant mechanisms, and serum cytokine levels in cancer patients: impact of an antioxidant treatment. J Environ Pathol Toxicol Oncol 22: 17-28, 2003.
33. Therasse P, Arbuck SG, Eisenhauer EA, et al. New guidelines to evaluate the response to treatment in solid tumors. J Natl Cancer Inst 92: 205-216, 2000.
34. WHO Handbook for reporting results of cancer treatment. No. 48. Geneva: World Health Organization Offset Publication, 1979.
35. Miller AB, Hodgstraten B, Staquet M, Winkler A. Reporting results of cancer treatment. Cancer 47: 207-214, 1981.
36. Dixon AR, Jackson L, Chan SY, Badley RA, Blamey RW. Continuous chemotherapy in responsive metastatic breast cancer: a role for tumor markers? Br J Cancer 68: 181-185, 1993.
37. Grimm EA, Mazumdar A, Zhang HZ, Rosenberg SA. Lymphokine-activated killer cell phenomenon. J Exp Med 155: 1823-1841, 1982.
38. Palmer PA, Atzpodien J, Philip T, et al. A comparison of 2 modes of administration of r-IL2: continuous intravenous infusion alone versus subcutaneus administration plus IFN-alpha in patients with advanced renal cell carcinoma. Cancer Biother 8: 123-135, 1993.
39. Gohring B, Riemann D, Rebmann U, Heynemann H, Schabel J, Langner J. Prognostic value of immunomonitoring of patients with renal cell carcinoma under therapy with IL-2/IFN-a in combination with 5-FU. Urol Res 24: 297-303, 1996.
40. Stanley KE. Prognostic factors for survival in patients with inoperable lung cancer. J Natl Cancer Inst 65: 25-32, 1980.
41. Maltoni M, Pirovano M, Nanni O. Biological indices predictive of survival in 519 italian terminally ill cancer patients. J Pain Symptom Manage 13: 1-9, 1997.
42. Riesco A. Five-year cancer cure: relation to total amount of peripheral lymphocytes and neutrophils. Cancer 25: 135-140, 1970.
43. Kim US, Papatestas AE, Aufses AH. Prognostic significance of peripheral lymphocyte counts and carcinoembryonic antigens in colorectal carcinoma. J Surg Oncol 8: 257-262, 1976.
44. Fumagalli L, Lissoni P, Di Felice G, Meregalli S, Valsuani G, Mengo S, Rovelli F. Pretreatment serum markers and lymphocyte response to interleukin-2 therapy. Br J Cancer 80: 407-411, 1999.
45. Mantovani G, Macciò A, Lai P, et al. Medroxyprogesterone acetate and megestrol acetate reduce cisplatin-induced serotonin release from human peripheral blood mononuclear cells (PBMC) of cancer patients. Oncol Rep 5: 121-124, 1998.
46. Mantovani G, Macciò A, Lai P, Massa E, Ghiani M, Santona MC. Cytokine activity in cancer-related anorexia/cachexia: Role of megestrol acetate and medroxyprogesterone acetate. Semin Oncol 25 (suppl 6): 45-52, 1998.
47. Mantovani G, Macciò A, Lai P, Massa E, Ghiani M, Santona MC. Cytokine involvement in cancer anorexia/cachexia. Role of megestrol acetate and medroxyprogesterone acetate on cytokine downregulation and improvement of clinical symptoms. Crit Rev Oncog 9: 99-106, 1998.
48. Anderson J, Cain K, Gelber R. Analysis of survival by tumor response. J Clin Oncol 1: 710-719, 1983.
49. Muss HB, Case LD, Richards F II, et al. Interrupted versus continuous chemotherapy in patients with metastatic breast cancer. N Engl J Med 325: 1342-1348, 1991.
50. O'Day SJ, Boasberg PD, Piro L, et al. Maintenance biotherapy for metastatic melanoma with interleukin-2 and granulocyte macrophage-colony stimulating factor improves survival for patients responding to induction concurrent biochemotherapy. Clin Cancer Res 8: 2775-2781, 2002.
51. Schiller JH, Morgan-Ihrig C, Levitt ML. Concomitant administration of IL-2 plus TNF-alpha in advanced non-small cell lung cancer. Am J Clin Oncol 18: 47-51, 1995.
52. Tester WJ, Kim KM, Krigel RL, et al. A randomized phase II study of interleukin-2 with and without beta-interferon for patients with advanced non-small cell lung cancer: an Eastern Cooperative Oncology Group study (PZ586). Lung Cancer 25: 199-206, 1999.
53. Lissoni P, Meregalli S, Fossati V, Paolorossi FB, arni S, Tancini G, Frigerio F. A randomized study of immunotherapy with low-dose s.c. IL-2 plus melatonin vs. chemotherapy with CDDP and etoposide as first-line therapy for advanced non-small cell lung cancer. Tumori 80: 464-467, 1994.
54. Blay JY, Negrier S, Combaret V, et al. Serum levels of IL-6 as a prognostic factor in metastatic renal cell carcinoma. Cancer Res 52: 3317-3322, 1992.
55. Lopez Hanninen E, Kirchner H, Atzpodien J. IL-2 based home therapy of metastatic renal cell carcinoma: risks and benefits in 215 consecutive single institution patients. J Urol 155: 19-25, 1996.
56. Lissoni P, Barni S, Tancini G, et al. Immunoendocrine therapy with interleukin-2 (IL-2) and medroxyprogesterone acetate (MPA): a randomized study with or without MPA in metastatic renal cancer patients during IL-2 maintenance treatment after response or stable disease to IL-2 subcutaneous therapy. Tumori 79: 246-249, 1993.
57. Buyse M, Thirion P, Carlson RW, Burzykowski T, Molenberghs G, Piedbois P. Relation between tumor response to first-line chemotherapy and survival in advanced colorectal cancer: a meta-analysis. Lancet 356: 373-378, 2000.