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Chemotherapy

Created the nation’s largest bone marrow and stem cell transplantation program, enabling treatment of about 850 patients with high-dose chemotherapy annually.

Pioneered the use of reduced, less-toxic doses of chemotherapy for bone marrow stem cell transplantation, resulting in lower mortality rates and the ability to perform transplant procedures in older patients, now a widely accepted standard of therapy.

Champlin R, Khouri I, Shimoni A, Gajewski J, Kornblau S, Molldrem J, Ueno N, Giralt S, Anderlini P. Harnessing graft-versus-malignancy: non-myeloablative preparative regimens for allogeneic haematopoietic transplantation, an evolving strategy for adoptive immunotherapy. Br J Haematol. 2000;111(1):18-29.

Giralt S, Estey E, Albitar M, van Besien K, Rondón G, Anderlini P, O’Brien S, Khouri I, Gajewski J, Mehra R, Claxton D, Andersson B, Beran M, Przepiorka D, Koller C, Kornblau S, Kørbling M, Keating M, Kantarjian H, Champlin R. Engraftment of allogeneic hematopoietic progenitor cells with purine analog-containing chemotherapy: harnessing graft-versus-leukemia without myeloablative therapy. Blood. 1997;89(12):4531-4536.

Khouri IF, Keating M, Körbling M, Przepiorka D, Anderlini P, O’Brien S, Giralt S, Ippoliti C, von Wolff B, Gajewski J, Donato M, Claxton D, Ueno N, Andersson B, Gee A, Champlin R. Transplant lite: induction of graft-versus-malignancy using fludarabine-based nonablative chemotherapy and allogeneic blood progenitor cell transplantation as treatment for lymphoid malignancies. J Clin Oncol. 1998;16(8):2817-2824.

Pioneered the use of chemotherapy given before surgery to shrink tumors of the breast, pancreas, lung and other organs, allowing them to be surgically removed with less damage to surrounding normal tissues.

Hortobagyi GN, Spanos W, Montague ED, Buzdar AU, Yap HY, Blumenschein GR. Treatment of locoregionally advanced breast cancer with surgery, radiotherapy and combination chemoimmunotherapy. Int J Radiat Oncol Biol Phys. 1983;9(5):643-650.

Hortobagyi GN, Blumenschein GR, Spanos W, Montague ED, Buzdar AU, Yap HY. Multimodal treatment of locoregionally advanced breast cancer. Cancer. 1983;51(5):763-768.

Roth JA, Fossella F, Komaki R, Ryan MB, Putnam JB, Lee JS, Dhingra H, De Caro L, Chasen M, McGavran M, Atkinson EN, Hong WK. A randomized trial comparing perioperative chemotherapy and surgery with surgery alone in resectable stage IIIA non-small-cell lung cancer. J Natl Cancer Inst. 1994;86(9):673-680.

Spitz FR, Abbruzzese JL, Lee JE, Pisters PW, Lowy AM, Fenoglio CJ, Cleary KR, Janjan NA, Goswitz MS, Rich TA, Evans DB. Preoperative and postoperative chemoradiation strategies in patients treated with pancreaticoduodenectomy for adenocarcinoma of the pancreas. J Clin Oncol. 1997;15(3):928-937.

Pisters PW, Abbruzzese JL, Janjan NA, Cleary KR, Charnsangavej C, Goswitz MS, Rich TA, Raijman I, Wolff RA, Lenzi R, Lee JE, Evans DB. Rapid-fractionation preoperative chemoradiation, pancreaticoduodenectomy and intraoperative radiation therapy for resectable pancreatic adenocarcinoma. J Clin Oncol. 1998;16(12):3843-3850.

Discovered the first successful chemotherapy (vincristine) for children with inoperable Wilms’ tumor, a kidney cancer.

Sullivan MP, Sutow WW, Cangir A, Taylor G. Vincristine sulfate in management of Wilms’ tumor. Replacement of preoperative irradiation by chemotherapy. JAMA. 1967;202(5):381-384.

Proposed the concept of combination chemotherapy for lymphoma and conducted the first clinical trials of CHOP (cyclophosphamide, adriamycin, vincristine and prednisone); efficacy later confirmed in multi-center trials conducted by the Southwest Oncology Group.

Gottlieb JA, Gutterman JU, McCredie KB, Rodriguez V, Frei E 3rd. Chemotherapy of malignant lymphoma with adriamycin. Cancer Research. 1973 Nov;33(11):3024-8.

McKelvey EM, Gottlieb JA, Wilson HE, Haut A, Talley RW, Stephens R, Lane M, Gamble JF, Jones SE, Grozea PN, Gutterman J, Coltman C, Moon TE. Hydroxyldaunomycin (Adriamycin) combination chemotherapy in malignant lymphoma. Cancer. 1976 Oct;38(4):1484-93.

Demonstrated the efficacy of paclitaxel (Taxol) against breast cancer, now standard treatment.

Holmes FA, Walters RS, Theriault RL, Forman AD, Newton LK, Raber MN, Buzdar AU, Frye DK, Hortobagyi GN. Phase II trial of Taxol, an active drug in the treatment of metastatic breast cancer.
J Natl Cancer Inst. 1991;83:1797-1805.

Demonstrated in early studies the efficacy of doxorubicin (Adriamycin) in combination with other drugs for the treatment of lymphoma, breast cancer, sarcomas, and other solid tumors.

Gottlieb JA, Gutterman JU, McCredie KB, Rodriguez V, Frei E III. Chemotherapy of malignant lymphoma with Adriamycin. Cancer Res. 1973;33(11):3024-3028.

Buzdar AU, Gutterman JU, Blumenschein GR, Hortobagyi GN, Tashima CK, Smith TL, Hersh EM, Freireich EJ, Gehan EA. Intensive postoperative chemoimmunotherapy for patients with stage II and stage III breast cancer. Cancer. 1978;41(3):1064-1075.

Gottlieb JA, Baker LH, Quagliana JM, Luce JK, Whitecar JP, Sinkovics JG, Rivkin SE, Brownlee R, Frei E. Chemotherapy of sarcomas with a combination of Adriamycin and dimethyl triazeno imidazole carboxamide. Cancer. 1972;30(6):1632-1638.

Led the clinical trial documenting the efficacy of temozolomide for glioblastoma, an often fatal brain tumor, leading to FDA approval.

Yung WK, Prados MD, Yaya-Tur R, Rosenfeld SS, Brada M, Friedman HS, Albright R, Olson J, Chang SM, O’Neill AM, Friedman AH, Bruner J, Yue N, Dugan M, Zaknoen S, Levin VA. Multicenter phase II trial of temozolomide in patients with anaplastic astrocytoma or anaplastic oligoastrocytoma at first relapse. J Clin Oncol. 1999;17(9):2762-2771.

Designed, synthesized and evaluated in brain tumor patients Berubicin (RTA774), the first blood-brain barrier-penetrating agent that is highly apoptotic.  

Fokt I, Conrad C, Madden T, Yung AW, Lang FF, Thapar N, Priebe W. The discovery and development of blood-brain barrier (BBB) penetrating anthracyclines for the treatment of brain tumors. Proceedings of  AACR-NCI-EORTC International Conference, Philadelphia, PA. A199, page 106, 2005.

Priebe W, Madden T, Fokt I, Johansen M, Conrad C.  Modular design of DNA binding agents capable of penetrating blood-brain barrier and targeting brain tumors. American Association for Cancer Research-American Chemical Society Joint Conference - Chemistry in Cancer Research: A Vital Partnership, San Diego, CA 2/4-2/8/2007.

Pioneered preclinical research on the mechanisms of anticancer effects of the spice curcumin, leading to current clinical trials of high-dose treatment for a variety of cancers.

Aggarwal BB, Kumar A, Bharti AC. Anticancer potential of curcumin: preclinical and clinical studies [review]. Anticancer Res. 2003;23(1A):363-398.

Demonstrated the efficacy of clofarabine, developed by MD Anderson researchers, against pediatric leukemia, adult myelodysplastic syndrome, and adult acute leukemia, leading to FDA approval.

Kantarjian HM, Gandhi V, Kozuch P, Faderl S, Giles F, Cortes J, O’Brien S, Ibrahim N, Khuri F, Du M, Rios MB, Jeha S, McLaughlin P, Plunkett W, Keating M. Phase I clinical and pharmacology study of clofarabine in patients with solid and hematologic cancers. J Clin Oncol. 2003;21(6):1167-1173.

Kantarjian H, Gandhi V, Cortes J, Verstovsek S, Du M, Garcia-Manero G, Giles F, Faderl S, O’Brien S, Jeha S, Davis J, Shaked Z, Craig A, Keating M, Plunkett W, Freireich EJ. Phase II clinical and pharmacologic study of clofarabine in patients with refractory or relapsed acute leukemia. Blood. 2003;102(7):2379-2386.

Jeha S, Gandhi V, Chan KW, McDonald L, Ramirez I, Madden R, Rytting M, Brandt M, Keating M, Plunkett W, Kantarjian H. Clofarabine, a novel nucleoside analog, is active in pediatric patients with advanced leukemia. Blood. 2004;103(3):784-789.

Faderl S, Gandhi V, O’Brien S, Bonate P, Cortes J, Estey E, Beran M, Wierda W, Garcia-Manero G, Ferrajoli A, Estrov Z, Giles FJ, Du M, Kwari M, Keating M, Plunkett W, Kantarjian H. Results of a phase I-II study of clofarabine in combination with cytarabine (ara-C) in relapsed and refractory acute leukemias. Blood. 2005;105(3):940-947.

Jeha S, Kantarjian H. Clofarabine for the treatment of acute lymphoblastic leukemia. Expert Rev Anticancer Ther. 2007;7(2):113-118.

Developed and secured FDA approval of Busulfex, an intravenous form of  busulfan that is now a standard chemotherapy agent used in bone marrow transplantation for leukemia.

Andersson BS, Gajewski J, Donato M, Giralt S, Gian V, Wingard J, Tarantolo S, Fernandez H, Hu WW, Blume K, Kashyap A, Forman SJ, Champlin RE. Allogeneic stem cell transplantation (BMT) for AML and MDS following IV busulfan and cyclophosphamide (IV BuCY). Bone Marrow Transplant. 2000;25(suppl 2):S35-S38.

Designed, synthesized, formulated in liposomes and patented Annaymcin, a drug highly active against multidrug-resistant tumors; currently in phase I/phase II clinical trials for patients with acute lymphocytic leukemia.

Priebe W, Perez-Soler R. Design tumor targeting of anthracyclines able to overcome multidrug resistance: a double-advantage approach.  Pharmac Ther 60: 215-34, 1993

Perez-Soler R, Ling Y-H, Zou Y, Priebe W.  Cellular pharmacology of the partially non-cross-resistant anthracycline Annamycin entrapped in liposomes in KB and KB-V1 cells. Cancer Chemother Pharmacol 34:P 109-18, 1994

Consoli U, Priebe W, Ling Y-H, Mahadevia R, Griffin M, Zhao S, Perez-Soler R, Andreeff M. The novel anthracycline Annamycin is not affected by P-glycoprotein-related multidrug resistance: comparison with idarubicin and doxorubicin in HL-60 leukemia cell lines. Blood 88:633-44, 1996

Pioneered gemcitabine chemotherapy for pancreatic cancer, currently the standard therapy.

Abbruzzese JL, Grunewald R, Weeks EA, Gravel D, Adams T, Nowak B, Mineishi S, Tarassoff P, Satterlee W, Raber MN, Plunkett W. A phase I clinical, plasma and cellular pharmacology study of gemcitabine. J Clin Oncol. 1991;9(3):491-498.

Demonstrated the efficacy of paclitaxel (Taxol) for non-small cell lung cancer.

Murphy WK, Fossella FV, Winn RJ, Shin DM, Hynes HE, Gross HM, Davilla E, Leimert J, Dhingra H, Raber MN, Krakoff IH, Hong WK. Phase II study of taxol in patients with untreated advanced non-small cell lung cancer. J Natl Cancer Inst. 1993;85(5):384-388.

Led the pivotal trial demonstrating the efficacy of rituximab in treating indolent B-cell non-Hodgkin’s lymphomas resistant to other chemotherapy regimens, which led to FDA approval of this monoclonal antibody.

McLaughlin P, Grillo-Lopez AJ, Link BK, Levy R., Czuczman MS, Williams ME, Heyman MR, Bence-Bruckler L., White CA, Cabanillas F, Jain V, Ho AD, Lister J, Wey K, Shen D, Dallaire BK. Rituximab chimeric anti-CD20 monoclonal antibody therapy for relapsed indolent lymphomas: half of patients respond to a four-dose treatment program. J Clin Oncol. 1998;16(8):2825-2833.

Developed the three-drug FND regimen that incorporated the nucleoside analog fludarabine into a highly effective regimen for patients with indolent lymphoma.

McLaughlin P, Hagemeister FB, Romaguera JE, Sarris AH, Pate O, Younes A, Swan F, KeatingM, Cabanillas F. Fludarabine, mitoxantrone, and dexamethasone: an effective new regimen for indolent lymphoma. J Clin Oncol. 1996;14(4):1262-1268.

Performed pivotal studies leading to FDA approval of nilotinib and dasatinib as frontline therapy for patients with newly diagnosed chronic myeloid leukemia.

Kantarjian H, Shah NP, Hochhaus A, Cortes J, Shah S, Ayala M, Moiraghi B, Shen Z, Mayer J, Pasquini R, Nakamae H, Huguet F, Boqué C, Chuah C, Bleickardt E, Bradley-Garelik MB, Zhu C, Szatrowski T, Shapiro D, Baccarani M. Dasatinib versus imatinib in newly diagnosed chronic-phase chronic myeloid leukemia. N Engl J Med 2010;362:2260-2270.

Saglio G, Kim DW, Issaragrisil S, le Coutre P, Etienne G, Lobo C, Pasquini R, Clark RE, Hochhaus A, Hughes TP, Gallagher N, Hoenekopp A, Dong M, Haque A, Larson RA, Kantarjian HM; ENESTnd Investigators. Nilotinib versus imatinib for newly diagnosed chronic myeloid leukemia. N Engl J Med 2010;362:2251-2259.


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