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Combination Chemotherapy: Clinical Considerations

  • Chapter
Antineoplastic and Immunosuppressive Agents Part I

Abstract

The experimental design for the evaluation of a single agent in cancer can be complex, and the results from different centers vary considerably. The variables involved in the evaluation of combinations of agents, as compared to single agents, increase substantially. Thus, in the construction of clinical trials involving combination chemotherapy, major emphasis should be given to the problem of experimental design.

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References

  • Acute Leukemia Group B: Acute lymphocytic leukemia in children. Maintenance therapy with methotrexate administered intermittently. J. Amer. med. Ass. 207, 923–928 (1969).

    Article  Google Scholar 

  • Acute Leukemia Group B: Unpublished data (1970).

    Google Scholar 

  • Alexanian, R.: Unpublished data of the Southwest Cancer Chemotherapy Study Group (1972).

    Google Scholar 

  • Alexanian, R., Hart, A., Khan, A.U., Lane, M., MoKelvey, E.M., Miguore, P. J., Stuokey, W.J.Jr., Wilson, H.E.: Treatment for multiple myeloma; combination chemotherapy with different melphalan dose regimens. J. Amer. med. Ass. 208, 1680–1685 (1969).

    Article  CAS  Google Scholar 

  • Allaire, F.J., Thieme, E.T., Korst, D.R.: Cancer chemotherapy with 5-fluorouracil alone and in combination with X-ray therapy. Cancer Chemother. Rep. 14, 59–75 (1961).

    PubMed  CAS  Google Scholar 

  • Ansfield, F.J.: Further clinical comparison between 5-fluoro-2′-deoxyuridine (5-FUDR) and 5-fluorouracil (5-FU). Proc. Amer. Ass. Cancer Res. 4, 2 (1963).

    Google Scholar 

  • Anspield, F. J., Ramirez, G., Korbitz, B.C., Daus, H.L., Jr.: Five drug therapy for advanced cancer: a phase I study. Cancer Chemother. Rep. 55, 183–188 (1971).

    Google Scholar 

  • Bern ARD, J.: Acute leukemia treatment. Cancer Res. 27, 2565–2569 (1967).

    Google Scholar 

  • Bernard, J., Boiron, M., Jaoquillat, E., Weill, M.: Rubidomycin: 400 patients with leukemia and other malignancies. Abstracts of the XII Congress of the Int. Society of Hemat., p. 5 (1968).

    Google Scholar 

  • Bodey, G.P., Freireich, E.J.: Unpublished data of Southwestern Cancer Chemotherapy Study Group (1972).

    Google Scholar 

  • Bodey, G.R., Luce, J.K., Harris, J.E., Frei, E., III: The effect of cytosine arabinoside on metastatic cancer and acute leukemia, p. 6. Abstracts of XII Congress, Inst. Soc. Hemat. (1968).

    Google Scholar 

  • Bodey, G.P., Rodriguez, V., Whiteoar, J.P., Hart, J., Freireich, E.J.: The treatment of acute leukemia in adults. In: Leukemia-Lymphoma, a collection of papers presented at the 14 th annual clinical conference at M. D. Anderson Hospital and Tumor Institute pp. 333–346. Chicago: Yearbook Medical Publishers, Inc. 1970.

    Google Scholar 

  • Bohannon, R.A., Miller, D.G., Diamond, H.: Vincristine in the treatment of lymphomas and leukemias. Cancer Res. 23, 613–621 (1963).

    PubMed  CAS  Google Scholar 

  • Bonnet, J.D., Brownlee, R.W.: Unpublished data of the Southwest Cancer Chemotherapy Study Group (1971).

    Google Scholar 

  • Brennan, M.J., Talley, R.W., Sandiego, E.L., Burrows, J.H., O’Brien, R.M., Vaitkeviciks, V.M., Horeyland, S.: Critical analysis of 594 cancer patients treated with 5-fluorouracil. In: Plattner, P.A. (Ed.): Proceedings of the international symposium of chemotherapy of cancer, pp. 148–150. New York: American Elsevier 1964.

    Google Scholar 

  • Burchenal, J.H.: Long term survivors in acute leukemia. In: Zarafonetis, C.J.D. (Ed.): Proceedings of the international conference on leukemia-lymphoma, pp. 469–474. Philadelphia: Lea Febiger 1968.

    Google Scholar 

  • Burchenal, J.H., Dollinger, M.R.: Cytosine arabinoside (NSC-63878) in combination with 6-mercaptopurine (NSC-755), methotrexate (NSC-740) or fluorouracil (NSC-19893) in L1210 mouse leukemia. Cancer Chemother. Rep. 51, 435–438 (1967).

    CAS  Google Scholar 

  • Calendi, E., DiMarco, A., Reggiani, M., Scarpinato, B., Valentini, L.: On physico-chemical interactions between daunomycin and nucleic acids. Biochim. biophys. Acta (Amst.) 103, 25–49 (1965).

    CAS  Google Scholar 

  • Carter, S.: Clinical trials and combination chemotherapy. Cancer Chemother. Rep. 2, 81–97 (1971).

    Google Scholar 

  • Coltman, C.A., Costanzi, J.J., Dudley, G.M., III., Haut, A., Lane, M., Gehan, E.A.: Further clinical studies of combination chemotherapy using cyclophosphamide, vincristine, methotrexate, and 5-fluorouracil. Amer. J. med. Sci. 261, 73–78 (1971).

    Article  PubMed  Google Scholar 

  • Cooper, R.G.: Combination chemotherapy in hormone resistant breast cancer. Proc. Amer. Ass. Cancer Res. 10, 15 (1969).

    Google Scholar 

  • Costanzi, J.J., Coltman, C.A.: Combination chemotherapy using cyclophosphamide, vincristine, methotrexate, and 5-fluorouracil. Cancer 23, 589–596 (1969).

    Article  PubMed  CAS  Google Scholar 

  • Crowther, D., Bateman, C.J.T., Vartan, C.P., Whttehouse, J.M.A., Malpas, J.S., Fairley, G.H., Scott, R.B.: Combination chemotherapy using L-asparaginase, daunorubicin, and cytosine arabinoside in adults with acute myelogenous leukemia. Brit. med. J. 4, 513–517 (1970).

    Article  PubMed  CAS  Google Scholar 

  • DeConti, R. C.: Procarbazine in the management of late Hodgkin’s disease. J. Amer. med. Ass. 215, 927–930 (1971).

    Article  CAS  Google Scholar 

  • Devita, V.T., Serpick, A.A., Carbone, P.P.: Combination chemotherapy in the treatment of advanced Hodgkin’s disease. Ann. intern. Med. 73, 881–895 (1970).

    PubMed  Google Scholar 

  • Djerassi, L. Romtnger, C.J., Kim, J., Turoui, J., Meyer, E.: Methotrexate — citrovorum in patients with lung cancer. Proc. Amer. Ass. Cancer Res. 11, 21 (1970).

    Google Scholar 

  • Eastern Cooperative Group in Solid Tumor Chemotherapy: Comparison of antimetabolites in the treatment of breast and colon cancer. J. Amer. med. Ass. 200, 770–778 (1967).

    Article  Google Scholar 

  • Elion, G.B., Callahan, S.N., Nathan, H., Biebee, S., Bundles, R.W., Hitchings, G.M.: Potentiation of inhibition of drug degradation: 6-substituted purines and xanthine oxidase. Biochem. Pharmacol. 12, 85–93 (1963).

    Article  CAS  Google Scholar 

  • Ellison, R.R.: Experience with fluorinated pyrimidines in adenocarcinoma of the lower intestinal tract. N. Y. J. Med. 62, 2364–2369 (1962).

    CAS  Google Scholar 

  • Ellison, R. R., Holland, J. F., Weil, M., Jacquillat, C., Boiron, M., Bernard, J., Sawttsky, A., Rosner, F., Gussott, B., Silver, R. T., Karamas, A., Cuttner, J., Spurr, C.L., Hayes, D.M., Blom, J., Leone, L.A., Maurani, F., Kyle, R., Hutchison, J.L., Forcier, R.J., Moon, J.N.: Arabinosyl cytosine: a useful agent in the treatment of acute leukemia in adults. Blood 32, 507–523 (1968).

    PubMed  CAS  Google Scholar 

  • Ezdinli, E.Z., Stutzman, L.: Vinblastine vs. nitrogen mustard therapy of Hodgkin’s disease. Cancer 22, 473–479 (1968).

    Article  PubMed  CAS  Google Scholar 

  • Ezdinli, E.Z., Stutzman, L., Aungst, C.W., Firat, D.: Corticosteroid therapy for lymphomas and chronic lymphocytic leukemia. Cancer 23, 900–909 (1969).

    Article  PubMed  CAS  Google Scholar 

  • Field, J.B.: 5-Fluorouracil (NCS 9893) treatment of advanced cancer in ambulatory patients. Cancer Chemother. Rep. 33, 45–49 (1963).

    PubMed  CAS  Google Scholar 

  • Frei, E., III.: Southwestern Chemotherapy Study Group data; manuscript in preparation, 1972.

    Google Scholar 

  • Frei, E., III, DeVita, V.T., Moxley, J.N., Carbone, P.P.: Approaches to improving the chemotherapy of Hodgkin’s disease. Cancer Res. 26, 1284–1289 (1966).

    PubMed  Google Scholar 

  • Frei, E., III., Freireich, E.J.: Progress and perspectives in the chemotherapy of acute leukemias. Advanc. Chemother. 2, 269–298 (1965).

    CAS  Google Scholar 

  • Frei, E., III., Freireich, E.J., Gehan, E., Pinley, D., Holland, J.F., Selawry, O., Haurami, F., Spurr, C.L., Hayes, D.M., Jones, G.W., Rothberg, H., Sodee, D.B., Runtles, R.W., Shroeder, L.R., Koogstraten, B., Wolman, I.J., Traggis, D.G., Cooper, T., Gerdel, B.R., Ebaugh, F., Taylor, R.: Studies of sequential and combination antmetabolite therapy in acute leukemia: 6-mercaptopurine and methotrexate, from the acute leukemia Group B. Blood 18, 431–454 (1961).

    Google Scholar 

  • Frei, E., III., Karon, M., Levin, R.M., Freireich, E.J., Taylor, R.J., Mananian, J., Selawry, O., Holland, J.F., Noogstraten, B., Wolman, J.J., Abir, E., Sawitsky, A., Lee, S., Mills, S.D., Bürgert, E.O., Jr., Spurr, C.L., Patterson, R.B., Ebaugh, F.G., James, G.W., III., Moon, J.N.: The effectiveness of combinations of antileukemic agents in inducing and maintaining remission in children with acute leukemia. Blood 26, 642–656 (1965).

    PubMed  Google Scholar 

  • Freireich, E. J., Gehan, E., Frei, E., III, Schroeder, L.R., Wolman, I. J., Anbori, R., Bürgerte, O., Mills, S.D., Pinkel, D., Selawry, O.S., Moon, J.N., Gendel, B.R., Spurr, G.L., Storrs, R. Maurani, F., Noogstraten, B., Lee, S.: The effect of 6-mercaptopurine on the duration of steroid-induced remission in acute leukemia: A model for evaluation of other potentially useful therapy. Blood 21, 699–716 (1963).

    CAS  Google Scholar 

  • Freireioh, E.J., Henderson, E.S., Karon, M.R., Frei, E., III.: The treatment of acute leukemia considered with respect to cell population kinetics. In: The proliferation and spread of neoplastic cells, pp. 441–452. Baltimore: Williams and Wilkins 1968.

    Google Scholar 

  • Gaudin, D., Yielding, K.L., Stabler, A., Brown, J.: The effect of DNA repair inhibitors on the response of tumors treated with x-ray and alkylating agents. Proc. Soc. exp. Biol. (N. Y.) 137, 202–206 (1971).

    CAS  Google Scholar 

  • Gee, T.S., Yu, K.P„ Clarkson, B.D.: Treatment of adult acute leukemia with arabinosyl cytosine and thioguanine. Cancer 23, 1019–1032 (1969).

    Article  PubMed  CAS  Google Scholar 

  • Gottlieb, J. A., Serpick, A. A.: Prolonged intravenous methotrexate therapy in the treatment of acute leukemia and solid tumors. Cancer Res. 30, 2132–2138 (1970).

    PubMed  CAS  Google Scholar 

  • Henderson, E.S.: Combination chemotherapy of acute lymphocytic leukemia of childhood. Cancer Res. 27, 2570–2572 (1967).

    PubMed  CAS  Google Scholar 

  • Henderson, E.S.: Treatment of acute leukemia. Ann. intern. Med. 69, 628–629 (1968).

    PubMed  CAS  Google Scholar 

  • Henderson, E.S.: Treatment of acute leukemia. Semin. Hemat. 6, 271–319 (1969).

    PubMed  CAS  Google Scholar 

  • Henderson, E. S., Samaha, R.J.: Evidence that drugs in multiple combinations have materially advanced the treatment of human malignancies. Cancer Res. 29, 2272–2280 (1969).

    CAS  Google Scholar 

  • Henderson, E.S., Serpick, A.A.: The effect of combination drug therapy and prophylactic oral antibiotic treatment in adult acute leukemia. Clin. Res. 15, 336 (1967).

    Google Scholar 

  • Henderson, E.S., Serpick, A.A., Leventhal, B.G., Henry, P.: Cytosine arabinoside infusions in adult and childhood acute myelocytic leukemia. Proc. Amer. Ass. Cancer Res. 9, 29 (1968).

    Google Scholar 

  • Hersh, E.M., Whttecar, J.P., Jr., MoCredie, K.B., Bodey, G.P., Freireich, E.J.: Chemotherapy, immunocompetence, immunosuppression and prognosis in acute leukemia. N. Engl. J. Med. 285, 1211–1216 (1971).

    Article  PubMed  CAS  Google Scholar 

  • Holland, J.F.: Clinical studies of unmaintained remission in acute lymphocytic leukemia. In: The proliferation and spread of neoplastic cells, pp. 453–462. Baltimore: Williams & Wilkins 1968.

    Google Scholar 

  • Holland, J.F., Glidewell, O.: Induction, consolidation, intensification, reinduction and maintenance chemotherapy of acute lymphocytic leukemia. Abstracts of the XII Congress, Int. Soc. Hemat., p. 9. 1968.

    Google Scholar 

  • Hoogstraten, B.: Cyclophosphamide in acute leukemia. Cancer chemother. Rep. 16, 167–171 (1962).

    PubMed  CAS  Google Scholar 

  • Hurley, J. D.: Treatment of advanced cancer with 5-fluorouracil. Acta Un. int. Cancer. 20, 363–365 (1964).

    CAS  Google Scholar 

  • Jacobs, E.M., Peters, F.C., Lttce, J.K., Zippin, C., Wood, D.A.: Mechlorethamine HCl and cyclophosphamide in the treatment of Hodgkin’s disease and the lymphomas. J. Amer. med. Ass. 203, 392–398 (1968).

    Article  CAS  Google Scholar 

  • Kaplan, H.S.: Long-term results of palliative and radical radiotherapy of Hodgkin’s disease. Cancer Res. 26, 1250–1252 (1966).

    PubMed  CAS  Google Scholar 

  • Karon, M., Freireich, E. J., Frei, E., III., Taylor, R., Wolman, I. J., Djerassi, I., Lee, S.L., Sawitsky, A., Hananian, J., Selawry, O., James, D., Jr., George, P., Patterson, R.B., Bttrgert I., Haurani, F.I., Oberfield, R.A., Macy, C.T., Hoogstraten, B., Blom, T.: The role of vincristine in the treatment of childhood acute leukemia. Clin. Pharmacol. Ther. 7, 332–339 (1966).

    PubMed  CAS  Google Scholar 

  • Kennedy, B. J.: Chemotherapy of colon cancer. Lancet 84, 131–133 (1964).

    CAS  Google Scholar 

  • Kennedy, B. J.: Hormonal therapies in breast cancer: Androgens versus estrogens. In: Breast cancer early and late, pp. 381–386. Chicago: Yearbook Medical Publishers 1970.

    Google Scholar 

  • Lefkowttz, E., Papac, R.J., Bertino, J.R.: Head and neck cancer. III. Toxicity of 24-hour infusions of methotrexate (NSC 740) and protection by leucovorin (NSC 3590) in patients with epidermoid carcinomas. Cancer Chemother. Rep. 51, 305–311 (1967).

    Google Scholar 

  • Leiktn, J.L., Brubaker, C., Hartmann, J.R., Murphy, M.L., Wolff, J.A., Perrin, E.: Varying prednisone dosage in remission induction of previously untreated childhood leukemia. Cancer 21, 346–351 (1968).

    Article  Google Scholar 

  • LePage, G.A.: Unpublished data (1972).

    Google Scholar 

  • LePage, G.A., Jones, M.: Further studies on mechanism of action of 6-thioguanine. Cancer Res. 21, 1590–1594 (1961).

    PubMed  CAS  Google Scholar 

  • Li, M. D., Whttmore, W.F., Jr., Golbey, R., Gragstald, M.: Effects of combined drug therapy on metastatic cancer of the testis. J. Amer. med. Ass. 174, 1291–1301 (1960).

    Article  CAS  Google Scholar 

  • Liegler, D.G., Henderson, E.S., Hahn, M.A., Oliverio, V.T.: The effect of organic acids on renal clearance of methotrexate in man. Clin. Pharmacol. Ther. 10, 849–857 (1969).

    PubMed  CAS  Google Scholar 

  • Livingston, R., Carter, S.: Single agents in cancer chemotherapy. New York: Plenum 1970.

    Google Scholar 

  • Livingston, R.B., Venditti, J.M., Cooney, D.A., Carter, S.K.: Glutamine antagonists in chemotherapy. Advanc. Pharmacol. Chemother. 8, 57–120 (1970).

    Article  CAS  Google Scholar 

  • Luce, J.K., Gamble, J.F., Wilson, N.E., Monto, R.W., Isaacs, B.L., Palmer, R.L., Coltman, CA., Jr., Hewlett, J. S., Gehan, E.A., Frei, E., III: Combined cyclophosphamide, vincristine and prednisone therapy of malignant lymphoma. Cancer 28, 306–317 (1971).

    Article  PubMed  CAS  Google Scholar 

  • MacKenzie, A.R.: Chemotherapy of metastatic testis cancer. Results in 154 patients. Cancer 19, 1369–1376 (1966).

    Article  PubMed  CAS  Google Scholar 

  • Mass, R.E.: A comparison of the effect of prednisone and a placebo in the treatment of multiple myeloma. Cancer Chemother. Rep. 16, 257–259 (1962).

    PubMed  CAS  Google Scholar 

  • Mellett, L.B., El Da Reer, S.M., Luce, J.K., Frei, E., III.: Activation of cyclophosphamide in various species. Pharmacologist 11, 273 (1969).

    Google Scholar 

  • Middleman, E., Luce, J. K., Frei, E., III.: Clinical trials with adriamycin. Cancer 28, 844–850 (1971).

    Article  PubMed  CAS  Google Scholar 

  • Mitchell, M.S., Wawro, N.W., DeConti, R.C., Kaplan, S.R., Papac, R., Berttno, J.R.: Effectiveness of high dose infusions of methotrexate followed by leucovorin in carcinoma of the head and neck. Cancer Res. 28, 1088–1094 (1968).

    PubMed  CAS  Google Scholar 

  • Moertel, C.G., Reitemeier, R.J., Kahn, R.G.: Therapy with the fluorinated pyrimidines. In: Moertel, C.G., Reitemeier, R.J. (Eds.): Advanced gastrointestinal cancer. Clinical management and chemotherapy, pp. 86–107. New York: Harper & Row 1969.

    Google Scholar 

  • Nathanson, L., Hall, T.C., Schilling, A., Miller, S.: Concurrent combination chemotherapy of human solid tumors: experience with a three-drug regimen and review of the literature. Cancer Res. 29, 419–425 (1969).

    PubMed  CAS  Google Scholar 

  • Piessens, W.F., Keimann, R., Legrtts, N., Kettson, J.C.: Effect of BCG on mammary tumor formulation and cellular immunity in DMBA-treated rats. Cancer Res. 31, 1061–1065 (1971).

    PubMed  CAS  Google Scholar 

  • Pinkel, D., Hernandez, K., Borella, L., Holton, C., Aur, R., Samoy, G., Pratt, C.: Drug dosage and remission duration in childhood lymphocytic leukemia. Cancer 27, 247–256 (1971).

    Article  PubMed  CAS  Google Scholar 

  • Pinkel, D., Pratt, C., Holton, C., James, D., Jr., Wrenn, E., Jr., Hustu, H.O.: Survival of children with neuroblastoma treated with combination chemotherapy. J. Pediat. 73, 928–931 (1968).

    Article  PubMed  CAS  Google Scholar 

  • Preisler, H.D., Henderson, E.S.: Effect of cytosine arabinoside and l, 3-bis-2-chloroethyl-1-nitrosourea on hematopoietic precursors in the mouse. J. nat. Cancer Inst. 47, 971–977 (1971).

    PubMed  CAS  Google Scholar 

  • Rochlin, D.B., Shiner, J., Langdon, E., Ottoman, R.: Use of 5-fluorouracil in disseminated solid neoplasms. Ann. Surg. 156, 105–113 (1962).

    Article  PubMed  CAS  Google Scholar 

  • Salmon, S.E.: Personal communication (1972).

    Google Scholar 

  • Salmon, S.E., Smith, B.A.: Immunoglobulin synthesis and total body tumor cell number in IgG multiple myeloma. J. clin. Invest. 49, 1114–1121 (1970).

    Article  PubMed  CAS  Google Scholar 

  • Sartorelli, A.C., Creasey, W.A.: Combination chemotherapy. In: Holland, J.F., Frei, E., III. (Eds.): Cancer medicine. Philadelphia: Lea & Febiger 1973.

    Google Scholar 

  • Schneck, S.A., Penn, J.: De Novo brain tumours in renal transplant recipients. Lancet 1, 983–986 (1971).

    Article  PubMed  CAS  Google Scholar 

  • Scott, J. L.: The effect of nitrogen mustard and maintenance chlorambucil in the treatment of advanced Hodgkin’s disease. Cancer Chemother. Rep. 27, 27–32 (1963).

    PubMed  CAS  Google Scholar 

  • Selawry, O.S.: New treatment schedule with improved survival in childhood leukemia: Intermittent parenteral daily oral administration of methotrexate for maintenance of induced remission. J. Amer. med. Ass. 194, 75–81 (1965).

    Google Scholar 

  • Sharp, G. S., Benefiel, W.W.: 5-Fluorouracil in the treatment of inoperable carcinoma of the colon and rectum. Cancer Chemother. Rep. 20, 97–101 (1962).

    PubMed  CAS  Google Scholar 

  • Skipper, H.E., Schabel, F.M., Trader, M.W., Laster, W.R., Simpson, L., Lloyd, M.M.: Basic and therapeutic trial results obtained in the spontaneous AKR leukemia (lymphoma) model. Cancer Chemother. Rep. (in press).

    Google Scholar 

  • Skipper, H.E., Schabel, F.M., Jr., Wilcox, W.S.: Experimental evaluation of potential anticancer agents. XXI. Scheduling of arabinosyl cytosine to take advantage of its 5-phase specificity against leukemia cells. Cancer Chemother. Rep. 51, 125–141 (1967).

    PubMed  CAS  Google Scholar 

  • Spear, P., Patno, M.: A comparative study of the effectiveness of HN2 and cyclophosphamide in bronchogenic carcinoma, Hodgkin’s disease and lymphosarcoma. Cancer Chemother. Rep. 16, 413–415 (1962).

    PubMed  CAS  Google Scholar 

  • Ultmann, J.E., Nixon, D.D.: The therapy of lymphoma. Semin. hemat. 6, 376–403 (1969).

    PubMed  CAS  Google Scholar 

  • Venditti, J.M., Humphreys, S.R., Mantel, N., Goldin, A.: Combined treatment of advanced leukemia (L1210) in mice with amethopterin and 6-mercaptopurine. J. nat. Cancer. Inst. 17, 631–638 (1956).

    PubMed  Google Scholar 

  • Weiss, A.J., Jackson, L.: The effect of 5-fluorouracil upon carcinomas of the gastrointestinal tract and related organs. Amer. J. Gastroent. 35, 138–146 (1961).

    PubMed  CAS  Google Scholar 

  • Whang-Peng, C.P., Knutsen, T.: Polyploidy in malignant melanoma. Cancer 25, 1216–1223 (1970).

    Article  PubMed  CAS  Google Scholar 

  • Whtteoar, J.P., Jr., Bodey, G.P., Freireich, E.J.: Combination chemotherapy (COAP) of adult acute leukemia. Proc. Amer. Ass. Cancer Res. 11, 83 (1970).

    Google Scholar 

  • Wolff, J. A., Brubaker, C.A., Murphy, M.L., Pierce, M. I., Severo, N.: Prednisone therapy of acute childhood leukemia: Prognosis and duration of response in 330 treated patients. J. Pediat. 70, 626–631 (1967).

    Article  PubMed  CAS  Google Scholar 

  • Zuelzer, W.W.: Implications of long-term survival in acute stem cell leukemia of childhood treated with composite cyclic therapy. Blood 24, 477–494 (1964).

    PubMed  CAS  Google Scholar 

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Authors
  1. Emil Frei III
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  2. Jeffrey A. Gottlieb
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Editors and Affiliations

  1. Department of Pharmacology, Yale University School of Medicine, New Haven, Connecticut, 06510, USA

    Alan C. Sartorelli (Professor) (Professor)

  2. Laboratory of Chemical Pharmacology, National Cancer Institute, National Istitutes of Health, Bethesda, Maryland, 20014, USA

    David G. Johns M. D.

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Frei, E., Gottlieb, J.A. (1974). Combination Chemotherapy: Clinical Considerations. In: Sartorelli, A.C., Johns, D.G. (eds) Antineoplastic and Immunosuppressive Agents Part I. Handbuch der experimentellen Pharmakologie / Handbook of Experimental Pharmacology, vol 38 / 1. Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-3-642-65678-1_21

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