nach oben

Indian Journal of Pediatrics

Erschienen in:

01.12.2012 | Special Article

Metronomic Chemotherapy in Progressive Pediatric Malignancies: Old Drugs in New Package

verfasst von: Ankur Bahl, Sameer Bakhshi

Erschienen in: Indian Journal of Pediatrics | Ausgabe 12/2012

Einloggen, um Zugang zu erhalten

Abstract

Despite intensive research in the field of cancer, many pediatric cancers are still incurable with current treatment protocols. Repetitive administration of conventional chemotherapy at maximal tolerated dose imposes many side effects that further limits the dosing and therefore decreases the anticancer effects. Usually limited options remain when a malignancy progresses after one or two lines of standard chemotherapy protocol. The goal of an oncologist at this point of time remains mainly palliative with an effort to halt the progression of cancer and improve quality of life. Metronomic chemotherapy is defined as the chronic administration of chemotherapeutic agents at relatively low, minimally toxic doses, and with no prolonged drug-free breaks. It is thought this type of chemotherapy inhibits tumor growth primarily through anti-angiogenic mechanisms, promoting apoptosis and immune- surveillance.

Steen RG. What is cancer? In Steen RG, Mirro J, eds. Childhood cancer: A handbook from St. Jude Children’s Research Hospital, Perseus Publishing Cambridge; 2000. pp. 3–10.

Canadian Cancer Society, National Cancer Institute of Canada, Statistics Canada, Provincial/Terretorial Cancer Registries, and Health Canada. Canadian Cancer Statistics 2004.

Canadian Cancer Statistics 2000. Cancer in Children aged 0–19 yrs. National Cancer Institute of Canada: Cancer Statistics 2000, Toronto, Canada, 2000. Accessed June 22nd, 2005. Online: http://www.cancer.ca/stats2000.childe.htm

Shimizu K, Oku N. Cancer anti-angiogenic therapy. Biol Pharm Bull. 2004;27:599–605.PubMedCrossRef

Fidler IJ, Ellis LM. Chemotherapeutic drugs: more really is not better. Nat Med. 2000;6:500–2.PubMedCrossRef

Kerbel RS. Inhibition of tumor angiogenesis as a strategy to circumvent acquired resistance to anti-cancer therapeutic agents. Bioessays. 1991;13:31–6.PubMedCrossRef

Kerbel RS. A cancer therapy resistant to resistance. Nature. 1997;390:335–6.PubMedCrossRef

Folkman J. Tumor angiogenesis: therapeutic implications. N Engl J Med. 1971;285:1182–6.PubMedCrossRef

Gasparini G. The rationale and future potential of angiogenesis inhibitors in neoplasia. Drugs. 1999;58:17–38.PubMedCrossRef

10.

Fox SB, Gasparini G, Harris AL. Angiogenesis: pathological, prognostic, and growth-factor pathways and their link to trial design and anticancer drugs. Lancet Oncol. 2001;2:278–89.PubMedCrossRef

11.

Miller KD, Sweeney CJ, Sledge Jr GW. Redefining the target: chemotherapeutics as antiangiogenics. J Clin Oncol. 2001;19:1195–206.PubMed

12.

Eberhard A, Kahlert S, Goede V, Hemmerlein B, Plate KH, Augustin HG. Heterogeneity of angiogenesis and blood vessel maturation in human tumors: implications for antiangiogenic tumor therapies. Cancer Res. 2000;60:1388–93.PubMed

13.

Klement G, Baruchel S, Rak J, et al. Continuous low-dose therapy with vinblastine and VEGF receptor-2 antibody induces sustained tumor regression without overt toxicity. J Clin Invest. 2000;105:R15–24.PubMedCrossRef

14.

Browder T, Butterfield CE, Kräling, et al. Antiangiogenic scheduling of chemotherapy improves efficacy against experimental drugresistant cancer. Cancer Res. 2000;60:1878–86.PubMed

15.

Kerbel RS, Kamen BA. The anti-angiogenic basis of metronomic chemotherapy. Nat Rev Cancer. 2004;4:423–36.PubMedCrossRef

16.

Dunn GP, Bruce AT, Ikeda H, Old LJ, Schreiber RD. Cancer immunoediting: from immunosurveillance to tumor escape. Nat Immunol. 2002;3:991–8.PubMedCrossRef

17.

Kosmaczewska A, Ciszak L, Potoczek S, Frydecka I. The significance of Treg cells in defective tumor immunity. Arch Immunol Ther Exp (Warsz). 2008;56:181–91.CrossRef

18.

Kono K, Kawaida H, Takahashi A, et al. CD4(+)CD25high regulatory T cells increase with tumor stage in patients with gastric and esophageal cancers. Cancer Immunol Immunother. 2006;55:1064–71.PubMedCrossRef

19.

Ghiringhelli F, Larmonier N, Schmitt E, et al. CD4+CD25+ regulatory T cells suppress tumor immunity but are sensitive to cyclophosphamide which allows immunotherapy of established tumors to be curative. Eur J Immunol. 2004;34:336–44.PubMedCrossRef

20.

Loeffler M, Krüger JA, Reisfeld RA. Immunostimulatory effects of low-dose cyclophosphamide are controlled by inducible nitric oxide synthase. Cancer Res. 2005;65:5027–30.PubMedCrossRef

21.

Lutsiak ME, Semnani RT, De Pascalis R, Kashmiri SV, Schlom J, Sabzevari H. Inhibition of CD4 (+) 25+ T regulatory cell function implicated in enhanced immune response by low-dose cyclophosphamide. Blood. 2005;105:2862–8.PubMedCrossRef

22.

Matsushima H, Takashima A. Cyclophosphamide, DCs, and Tregs. Blood. 2010;115:4322–4.PubMedCrossRef

23.

Tanaka H, Matsushima H, Mizumoto N, Takashima A. Classification of chemotherapeutic agents based on their differential in vitro effects on dendritic cells. Cancer Res. 2009;69:6978–86.PubMedCrossRef

24.

Bergers G, Benjamin LE. Tumorigenesis and the angiogenic switch. Nat Rev Cancer. 2003;3:401–10.PubMedCrossRef

25.

Audia S, Nicolas A, Cathelin D, et al. Increase of CD4+ CD25+ regulatory T cells in the peripheral blood of patients with metastatic carcinoma:A phase I clinical trial using cyclophosphamide and immunotherapy to eliminate CD4+ CD25+T lymphocytes. Clin Exp Immunol. 2007;150:523–30.PubMedCrossRef

26.

Tsujii M, Kawano S, Tsuji S, Sawaoka H, Hori M, DuBois RN. Cyclooxygenase regulates angiogenesis induced by colon cancer cells. Cell. 1998;93:705–16.PubMedCrossRef

27.

Masferrer JL, Leahy KM, Koki AT, et al. Antiangiogenic and antitumour activities of cyclooxygenase-2 inhibitors. Cancer Res. 2000;60:1306–11.PubMed

28.

Gupta RA, Dubois RN. Combinations for cancer prevention. Nat Med. 2000;6:974–5.PubMedCrossRef

29.

Hsueh CT, Chiu CF, Kelsen DP, Schwartz GK. Selective inhibition of cyclooxygenase-2 enhances mitomycin-C-induced apoptosis. Cancer Chemother Pharmacol. 2000;45:389–96.PubMedCrossRef

30.

D’Amato RJ, Loughnan MS, Flynn E, Folkman J. Thalidomide is an inhibitor of angiogenesis. Proc Natl Acad Sci USA. 1994;91:4082–5.PubMedCrossRef

31.

Yoneda T, Alsina MA, Chavez JB, Bonewald L, Nishimura R, Mundy GR. Evidence that tumour necrosis factor plays a pathogenetic role in the paraneoplastic syndromes of cachexia, hypercalcaemia, and leukocytosis in a human tumour in nude mice. J Clin Invest. 1991;87:977–85.PubMedCrossRef

32.

Cabral FR. Isolation of Chinese hamster ovary cell mutants requiring the continuous presence of taxol for cell division. J Cell Biol. 1983;97:22–9.PubMedCrossRef

33.

Wong NS, Buckman RA, Clemons M, et al. Phase I/II trial of metronomic chemotherapy with daily dalteparin and cyclophosphamide, twice-weekly methotrexate, and daily prednisone as therapy for metastatic breast cancer using vascular endothelial growth factor and soluble vascular endothelial growth factor receptor levels as markers of response. J Clin Oncol. 2010;28:723–30.PubMedCrossRef

34.

Garcia AA, Hirte H, Fleming G, et al. Phase II clinical trial of bevacizumab and low-dose metronomic oral cyclophosphamide in recurrent ovarian cancer: a trial of the California, Chicago, and Princess Margaret Hospital phase II consortia. J Clin Oncol. 2008;26:76–82.PubMedCrossRef

35.

Sarmiento R, Gasparini G. Antiangiogenic metronomic chemotherapy. Onkologie. 2008;31:161–2.PubMedCrossRef

36.

Patil V, Noronha V, D’cruz AK, Banavali SD, Prabhash K. Metronomic chemotherapy in advanced oral cancers. J Cancer Res Ther. 2012;8:S106–10.PubMedCrossRef

37.

Sterba J, Pavelka Z, Slampa P. Concomitant radiotherapy and metronomic temozolomide in pediatric high-risk brain tumors. Neoplasma. 2002;49:117–20.PubMed

38.

Kieran MW, Turner CD, Rubin JB, et al. A feasibility trial of antiangiogenic (metronomic) chemotherapy in pediatric patients with recurrent or progressive cancer. J Pediatr Hematol Oncol. 2005;27:573–81.PubMedCrossRef

39.

Fousseyni T, Diawana M, Pasquier E, André N. Children treated with metronomic chemotherapy in a low-income country: METRO-MALI-01. J Pediatr Hematol Oncol. 2011;33:31–4.PubMedCrossRef

40.

Stempak D, Gammon J, Halton J, Moghrabi A, Koren G, Baruchel SA. pilot pharmacokinetic and antiangiogenic biomarker study of celecoxib and low-dose metronomic vinblastine or cyclophosphamide in pediatric recurrent solid tumors. J Pediatr Hematol Oncol. 2006;28:720–8.PubMedCrossRef

41.

Choi LM, Rood B, Kamani N, et al. Feasibility of metronomic maintenance chemotherapy following high-dose chemotherapy for malignant central nervous system tumors. Pediatr Blood Cancer. 2008;50:970–5.PubMedCrossRef

42.

Minturn JE, Janss AJ, Fisher PG, et al. A phase II study of metronomic oral topotecan for recurrent childhood brain tumors. Pediatr Blood Cancer. 2011;56:39–44.PubMedCrossRef

43.

Bocci G, Tuccori M, Emmenegger U, et al. Cyclophosphamide methotrexate ‘metronomic’ chemotherapy for the palliative treatment of metastatic breast cancer. A comparative pharmacoeconomic evaluation. Ann Oncol. 2005;16:1243–52.PubMedCrossRef

44.

De Vita S, De Matteis S, Laurenti L, et al. Secondary Ph+ acute lymphoblastic leukemia after temozolomide. Ann Hematol. 2005;84:760–2.PubMedCrossRef

45.

Rome A, André N, Scavarda D, et al. Metronomic chemotherapy induced bilateral subdural hematoma in a child with meningeal carcinomatosis. Pediatr Blood Cancer. 2009;53:246–7.PubMedCrossRef

Titel: Metronomic Chemotherapy in Progressive Pediatric Malignancies: Old Drugs in New Package
verfasst von: Ankur Bahl
Sameer Bakhshi
Publikationsdatum: 01.12.2012
Verlag: Springer-Verlag
Erschienen in: Indian Journal of Pediatrics / Ausgabe 12/2012
Print ISSN: 0019-5456
Elektronische ISSN: 0973-7693
DOI: https://doi.org/10.1007/s12098-012-0759-z

Update Pädiatrie

Bestellen Sie unseren Fach-Newsletter und bleiben Sie gut informiert.

Newsletter bestellen

Live-Webinar "Urologie und Sexualmedizin in der Praxis"

Springer Medizin

Metronomic Chemotherapy in Progressive Pediatric Malignancies: Old Drugs in New Package

Abstract

Neu im Fachgebiet Pädiatrie

Ähnliche Überlebensraten nach Reanimation während des Transports bzw. vor Ort

Alter der Mutter beeinflusst Risiko für kongenitale Anomalie

Begünstigt Bettruhe der Mutter doch das fetale Wachstum?

Bei Amblyopie früher abkleben als bisher empfohlen?

Update Pädiatrie

Live-Webinar "Urologie und Sexualmedizin in der Praxis"

Springer Medizin

Abstract

Bitte loggen Sie sich ein, um Zugang zu diesem Inhalt zu erhalten

Weitere Artikel der Ausgabe 12/2012

Enteric Fever Presenting as Secondary Hemophagocytic Lymphohistiocytosis

Antiretroviral Therapy in Children: Recent Advances

Immunization of HIV Infected Children

Pediatric Intensive Care Unit: An Essential Service to Improve Survival of Childhood Cancer in Developing World

Analysis of Short Stature Cases Referred for Genetic Evaluation

Outcome of Meningitis among Children Less than 2-y-old in Haryana

Neu im Fachgebiet Pädiatrie

Ähnliche Überlebensraten nach Reanimation während des Transports bzw. vor Ort

Alter der Mutter beeinflusst Risiko für kongenitale Anomalie

Begünstigt Bettruhe der Mutter doch das fetale Wachstum?

Bei Amblyopie früher abkleben als bisher empfohlen?

Update Pädiatrie