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Combination Therapies

Led a clinical trial demonstrating the superiority of chemoradiation over radiation alone for advanced cervical cancer, changing the standard of care.

Morris M, Eifel PJ, Lu J, Grigsby PW, Levenback C, Stevens RE, Rotman M, Gershenson DM, Mutch DG. Pelvic radiation with concurrent chemotherapy compared with pelvic and para-aortic radiation for high-risk cervical cancer. N Engl J Med. 1999;340(15):1137-1143.

Demonstrated that trastuzumab (Herceptin), given with chemotherapy, reduces recurrence of breast cancer after tumor excision and radiation therapy.

Buzdar AU, Ibrahim NK, Francis D, Booser DJ, Thomas ES, Theriault RL, Pusztai L, Green MC, Arun BK, Giordano SH, Cristofanilli M, Frye DK, Smith TL, Hunt KK, Singletary SE, Sahin AA, Ewer MS, Buchholz TA, Berry D, Hortobagyi GN. Significantly higher pathological complete remission rate after neoadjuvant therapy with trastuzumab, paclitaxel and epirubicin chemotherapy: results of a randomized trial in human epidermal growth factor receptor 2-positive operable breast cancer, paclitaxel and epirubicin chemotherapy: results of a randomized trial in human epidermal growth factor receptor 2-positive operable breast cancer. J Clin Oncol. 2005;23(16):3676-3685.

Buzdar AU, Valero V, Ibrahim NK, Francis D, Broglio KR, Theriault RL, Pusztai L, Green MC, Singletary SE, Hunt KK, Sahin AA, Esteva F, Symmans WF, Ewer MS, Buchholz TA, Hortobagyi GN. Neoadjuvant therapy with paclitaxel followed by 5-fluorouracil, epirubicin, and cyclophosphamide chemotherapy and concurrent trastuzumab in human epidermal growth factor receptor 2-positive operable breast cancer: an update of the initial randomized study population and data of additional patients treated with the same regimen. Clin Cancer Res. 2007;13(1):228-233.

Pioneered a combined-modality triple treatment strategy for the successful management of locally advanced inflammatory breast cancers, now the standard of care.

Yang CH, Cristofanilli M. Systemic treatments for inflammatory breast cancer. Breast Disease. 2006;22(1):55-65.

Introduced doxorubicin (Adriamycin) in a three-drug combination for the treatment of advanced breast cancer, now the standard of care in much of the world.

Gutterman JU, Cardenas JO, Blumenschein GR, Hortobagyi G, Burgess MA, Livingston RB, Mavligit GM, Freireich EJ, Gottlieb JA, Hersh EM. Chemoimmunotherapy of advanced breast cancer: prolongation of remission and survival with BCG. British Medical Journal. 1976;2(6046):1222-1225.

Introduced doxorubicin (Adriamycin) in combination with other agents in adjuvant chemotherapy to reduce the risk of breast cancer recurrence; this is currently the accepted standard therapy.

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.

Buzdar AU, Blumenschein GR, Gutterman JU, Tashima CK, Hortobagyi GN, Smith TL, Campos LT, Wheeler WL, Hersh EM, Freireich EJ, Gehan EA. Postoperative adjuvant chemotherapy with 5-fluorouracil, doxorubicin, cyclophosphamide and BCG: a follow-up report. JAMA. 1979;242(14):1509-1513.

Showed that adding pamidronate, a bone growth promoter, to chemotherapy or hormone therapy reduces skeletal complications from breast cancer; this is currently the standard of care.

Hortobagyi GN, Theriault RL, Porter L, Blayney D, Lipton A, Sinoff C, Wheeler H, Simeone JF, Seaman J, Knight RD; for Protocol 19 Aredia Breast Cancer Study Group. Efficacy of pamidronate in reducing skeletal complications in patients with breast cancer and lytic bone lesions. N Engl J Med. 1996;335(24):1785-1791.

Hortobagyi GN, Theriault RL, Lipton A, Porter L, Blayney D, Sinoff C, Wheeler H, Simeone JF, Seaman JJ, Knight RD, Heffernan M, Mellars K, Reitsma DJ; for Protocol 19 Aredia Breast Cancer Study Group. Long-term prevention of skeletal complications of metastatic breast cancer with pamidronate. J Clin Oncol. 1998;16(6):2038-2044.

Theriault RL, Lipton A, Hortobagyi GN, Leff R, Glück S, Stewart JF, Costello S, Kennedy I, Simeone J, Seaman JJ, Knight RD, Mellars K, Heffernan M, Reitsma DJ; for Protocol 18 Aredia Breast Cancer Study Group. Pamidronate reduces skeletal morbidity in women with advanced breast cancer and lytic bone lesions: a randomized, placebo-controlled trial. J Clin Oncol. 1999;17(3):846-854.

Combined chemotherapy with bone-targeting radionuclides for the treatment of hormone-refractory prostate cancer; patients showed prolonged survival after this treatment compared with chemotherapy alone.

Tu SM, Millikan RE, Mengistu B, Delpassand ES, Amato RJ, Pagliaro LC, Daliani D, Papandreou CN, Smith TL, Kim J, Podoloff DA, Logothetis CJ. Bone-targeted therapy for advanced androgen-independent carcinoma of the prostate: a randomized phase II trial. Lancet. 2001;357(9253):336-341. Erratum in: Lancet. 2001;357(9263):1210.

Demonstrated that adding rituximab to chemotherapy improves response to chemotherapy for patients with chronic lymphocytic leukemia and lymphoma, now a standard therapy.

Keating MJ, O’Brien S, Lerner S, Wierda W, Kantarjian H. Chemoimmunotherapy with fludarabine (F), cyclophosphamide (C), and rituximab (R) improves complete response (CR), remission duration and survival as initial therapy of chronic lymphocytic leukemia (CLL). J Clin Oncol. 2004;22(14S):6565.

Demonstrated the efficacy of fludarabine and alemtuzumab in chronic lymphocytic leukemia, leading to FDA approval.

Keating MJ, Kantarjian H, Talpaz M, Redman J, Koller C, Barlogie B, Velasquez W, Plunkett W, Freireich EJ, McCredie KB. Fludarabine: a new agent with major activity against chronic lymphocytic leukemia. Blood. 1989;74(1):19-25.

Keating MJ, O’Brien S, Lerner S, Wierda W, Kantarjian H. Chemoimmunotherapy with fludarabine (F), cyclophosphamide (C), and rituximab (R) improves complete response (CR), remission duration and survival as initial therapy of chronic lymphocytic leukemia (CLL). J Clin Oncol. 2004;22(14S):6565.

Discovered that the anti-EGF receptor antibody cetuximab (Erbitux) plus radiation therapy had synergistic effects against head-and-neck cancer in a preclinical model; this discovery led to a successful clinical trial and FDA approval of this combination therapy.

Milas L, Mason K, Hunter N, Petersen S, Yamakawa M, Ang K, Mendelsohn J, Fan Z. In vivo enhancement of tumor radioresponse by C225 antiepidermal growth factor receptor antibody. Clin Cancer Res. 2000;6(2):701-708.

Nasu S, Ang KK, Fan Z, Milas L. C225 antiepidermal growth factor receptor antibody enhances tumor radiocurability. Int J Radiat Oncol Biol Phys. 2001;51(2):474-477.

Demonstrated that combining radiation with an antibody (C225) that targets an important receptor in tumor cells improves the survival of patients with head and neck cancer.

Bonner JA, Harari PM, Giralt J, Azarnia N, Shin DM, Cohen RB, Jones CU, Sur R, Raben D, Jassem J, Ove R, Kies MS, Baselga J, Youssoufian H, Amellal N, Rowinsky EK, Ang KK. Radiotherapy plus cetuximab for squamous-cell carcinoma of the head and neck. New Engl J Med. 2006;354(6):567-578.

Ang KK, Berkey BA, Tu X, Zhang HZ, Katz R, Hammond EH, Fu KK, Milas L. Impact of epidermal growth factor receptor expression on survival and pattern of relapse in patients with advanced head and neck carcinoma. Cancer Res. 2002;62(24):7350-7356.

Led an international study that demonstrated improved survival in patients with stage II papillary or follicular thyroid cancer treated with total thyroidectomy, adjuvant radioactive iodine, and thyroid hormone suppression therapy.

Jonklaas J, Sarlis NJ, Litofsky D, Ain KB, Bigos ST, Brierley JD, Cooper DS, Haugen BR, Ladenson PW, Magner J, Robbins J, Ross DS, Skarulis M, Maxon HR, Sherman SI. Outcomes of patients with differentiated thyroid carcinoma following initial therapy.  Thyroid. 2006 Dec;16(12):1229-1242.

Demonstrated that chemotherapy given concurrently with radiation for cervical cancer is superior to the historical standard of using radiation alone.

Eifel PJ, Winter K, Morris M, Levenback C, Grigsby PW, Cooper J, Rotman M, Gershenson D, Mutch DG. Pelvic irradiation with concurrent chemotherapy versus pelvic and para-aortic irradiation for high-risk cervical cancer: an update of radiation therapy oncology group trial (RTOG) 90-01. J Clin Oncol. 2004;22(5):872-880.

Showed that all patients with advanced primary breast tumors, even those with an excellent response to chemotherapy, benefit from radiation after mastectomy. Also found that patients with early-stage breast cancer who have no lymph node metastases after chemotherapy and who then undergo mastectomy may not require radiation.

Buchholz TA, Tucker SL, Masullo L, Kuerer HM, Erwin J, Salas J, Frye D, Strom EA, McNeese MD, Perkins G, Katz A, Singletary SE, Hunt KK, Buzdar AU, Hortobagyi GN. Predictors of local-regional recurrence after neoadjuvant chemotherapy and mastectomy without radiation. J Clin Oncol 2002;20(1):17-23.

Huang EH, Tucker SL, Strom EA, McNeese MD, Kuerer HM, Buzdar AU, Valero V. Perkins GH, Schechter NR, Hunt KK, Sahin AA, Hortobagyi GN, Buchholz TA. Postmastectomy radiation improves local-regional control and survival for selected patients with locally advanced breast cancer treated with neoadjuvant chemotherapy and mastectomy. J Clin Oncol 2004;22:4691-4699.

Buchholz TA, Lehman CD, Harris JR, Pockaj BA, Khouri N, Hylton NF, Miller MJ, Whelan T, Pierce LJ, Esserman LJ, Newman LA, Smith BL, Bear HD, Mamounas EP. Statement of the science concerning loco-regional treatments after preoperative chemotherapy for breast cancer: a National Cancer Institute Conference. J Clin Oncol 2008;26(5):791-797.

Conducted the first trial of preoperative trastuzumab (Herceptin) among patients with HER2+ breast cancer, which demonstrated that adding Herceptin to standard chemotherapy achieves a complete response in 65% of patients. This combination is now accepted in the US as a standard therapy for this subset of patients.

Mittendorf EA, Wu Y, Meric-Bernstam F, Hunt KK, Dawood S, Esteva FJ, Buzdar AU, Chen H, Eksambi S, Hortobagyi GN, Baselga J, Gonzalez-Angulo AM. Loss of HER2 amplification following trastuzumab-based neoadjuvant systemic therapy and survival outcomes. Clin Cancer Res 2009;15(23):7381-7388.

Buzdar AU, Ibrahim NK, Francis D, Booser DJ, Thomas ES, Theriault RL, Pusztai L, Green MC, Arun BK, Giordano SH, Cristofanilli M, Frye DK, Smith TL, Hunt KK, Singletary SE, Sahin AA, Ewer MS, Buchholz TA, Berry D, Hortobagyi GN. Significantly higher pathologic complete remission rate after neoadjuvant therapy with trastuzumab, paclitaxel, and epirubicin chemotherapy: results of a randomized trial in human epidermal growth factor receptor 2-positive operable breast cancer. J Clin Oncol 2005;23:3676-3685.

Buzdar AU, Valero V, Ibrahim NK, Francis D, Broglio KR, Theriault RL, Pusztai L, Green MC, Singletary SE, Hunt KK, Sahin AA, Esteva F, Symmans WF, Ewer MS, Buchholz TA, Hortobagyi GN. Neoadjuvant therapy with paclitaxel followed by 5-fluorouracil, epirubicin, and cyclophosphamide chemotherapy and concurrent trastuzumab in human epidermal growth factor receptor 2-positive operable breast cancer: an update of the initial randomized study population and data of additional patients treated with the same regimen. Clin Cancer Res 2007;13:228-33.


© 2014 The University of Texas MD Anderson Cancer Center