|
|
|
|
|
|
||
|
|
||||
|
|
||||
|
||||
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Clinical Therapy Trials - Outcome |
Department of Neurology, Oregon Health Sciences University, Portland, OR 97201-3098 (N.D.D., P.G., L.L.M., E.A.N.); Childrens Center for Cancer and Blood Diseases, Childrens Hospital of Los Angeles, Los Angeles, CA 90027 (C.P.A.); Department of Pediatrics, M.D. Anderson Cancer Center, Houston, TX 99030 (W.A.B.); London Regional Cancer Center, London, Ontario, Canada N6A 4L6 (J.G.C.); Neuro-Oncology Program, University of California, Reed Neurological Research Center, Los Angeles, CA 90095-1769 (T.C.); University of Pennsylvania Medical Center, Philadelphia, PA 19104-6160 (S.L.E.); Department of Neurosurgery, University of Minnesota, Minneapolis, MN 55455 (W.A.H.); Department of Neurosurgery, Medical University of South Carolina, Charleston, SC 29425-2272 (S.J.P.); Hematology and Medical Oncology, Cleveland Clinic Foundation, Cleveland, OH 44195 (D.P.); Neuro-Oncology Center, Hadassah Hebrew University Hospital, Jerusalem, Israel 91120 (T.S.)
2 Address correspondence and reprint requests to Edward A. Neuwelt, Oregon Health Sciences University, Department of Neurology, 3181 S.W. Sam Jackson Park Rd.-L603, Portland, OR 97201-3098.
Abstract
Therapeutic options for the treatment of malignant brain tumors have been limited, in part, because of the presence of the blood-brain barrier. For this reason, the Sixth Annual Meeting of the Blood-Brain Barrier Disruption Consortium, the focus of which was the "Importance of Dose Intensity in Neuro-Oncology Clinical Trials," was convened in April 2000, at Government Camp, Mount Hood, Oregon. This meeting, which was supported by the National Cancer Institute, the National Institute of Neurological Disorders and Stroke, and the National Institute of Deafness and Other Communication Disorders, brought together clinicians and basic scientists from across the U.S. to discuss the role of dose intensity and enhanced chemotherapy delivery in the treatment of malignant brain tumors and to design multicenter clinical trials. Optimizing chemotherapy delivery to the CNS is crucial, particularly in view of recent progress identifying certain brain tumors as chemosensitive. The discovery that specific constellations of genetic alterations can predict which tumors are chemoresponsive, and can therefore more accurately predict prognosis, has important implications for delivery of intensive, effective chemotherapy regimens with acceptable toxicities. This report summarizes the discussions, future directions, and key questions regarding dose-intensive treatment of primary CNS lymphoma, CNS relapse of systemic non-Hodgkin's lymphoma, anaplastic oligodendroglioma, high-grade glioma, and metastatic cancer of the brain. The promising role of cytoenhancers and chemo-protectants as part of dose-intensive regimens for chemosensitive brain tumors and development of improved gene therapies for malignant gliomas are discussed.
References
Abrey, L.E., DeAngelis, L.M., and Yahalom, J. (1998) Long-term survival in primary CNS lymphoma. J. Clin. Oncol. 16,859 -863.[Abstract]
Abrey, L.E., Rosenblum, M.K., Papadopoulos, E., Childs, B.H., and Finlay, J.L. (1999) Highdose chemotherapy with autologous stem cell rescue in adults with malignant primary brain tumors. J. Neurooncol. 44,147 -153.[CrossRef][Medline]
Ahles, T.A., Silberfarb, P.M., Herndon, J., II, Maurer, L.H., Kornblith, A.B., Aisner, J., Perry, M.C., Eaton, W.L., Zacharski, L.L., Green, M.R., and Holland, J.C. (1998) Psychologic and neuropsychologic functioning of patients with limited small-cell lung cancer treated with chemotherapy and radiation therapy with or without warfarin: A study by the cancer and leukemia group B. J. Clin. Oncol. 16,1954 -1960.[Abstract]
Alavi, J.B., and Eck, S.L. (2000) Gene therapy for malignant gliomas. Expert Opin. Biol. Ther. In press.
Anderson, C.P., Tsai, J.M., Meek, W.E., Liu, R.M., Tang, Y., Forman, H.J., and Reynolds, C.P. (1999a) Depletion of glutathione by buthionine sulfoxine is cytotoxic for human neuroblastoma cell lines via apoptosis. Exp. Cell Res. 246,183 -192.[CrossRef][Web of Science][Medline]
Anderson, C.P., Seeger, R.C., Matthay, K.K., Neglia, J.P., Bailey, H.H., Meek, W., and Reynolds, C.P. (1999b) Buthionine sulfoximine (BSO) and melphalan (L-PAM) are active against recurrent neuroblastoma. Med. Pediatr. Oncol. 33,158 . (Abstract)[CrossRef]
Anderson, C.P., Keshelava, N., Meek, W.H., Satake, N., Reynolds, C.P. (2000) Buthionine sulfoximine (BSO) synergises the action of melphalan (L-PAM) for neuroblastoma cell lines established after disease progression in intensively treated patients. Med. Pediatr. Onco. In press.
Bigner, D.D., Brown, M.T., Friedman, A.H., Coleman, R.E., Akabani, G., Friedman, H.S., Thorstad, W.L., McLendon, R.E., Bigner, S.H., Zhao, X.G., Pegram, C.N., Wikstrand, C.J., Herndon, J.E., Vick, N.A., Paleologos, N., Cokgor, I., Provenzale, J.M., and Zalutsky, M.R. (1998) Iodine-131-labeled antitenascin monoclonal antibody 81C6 treatment of patients with recurrent malignant gliomas: Phase I trial results. J. Clin. Oncol. 16,2202 -2212.[Abstract]
Blay, J.-Y., Conroy, T., Chevreau, C., Thyss, A., Quesnel, N., Eghbali, H., Bouabdallah, R., Coiffier, B., Wagner, J.P., Le Mevel, A., Dramais-Marcel, D., Baumelou, E., Chauvin, F., and Biron, P. (1998) High-dose methotrexate for the treatment of primary cerebral lymphomas: Analysis of survival and late neurologic toxicity in a retrospective series. J. Clin. Oncol. 16,864 -871.[Abstract]
Bollen, E.L., Brouwer, R.E., Hamers, S., Hermans, J., Kluin, M.,
Sankatsing, S.U., A-Tjak, R.V., Charvat, M.V., and Kluin-Nelemans, J.C.
(1997) Central nervous system relapse in non-Hodgkin lymphoma: A
single-center study of 532 patients. Arch. Neurol.
54,854
-859.
Cairncross, J.G., Ueki, K., Zlatescu, M.C., Lisle, D.K.,
Finkelstein, D.M., Hammond, R.R., Silver, J.S., Stark, P.C., MacDonald, D.R.,
Ino, Y., Ramsay, D.A., and Louis, D.N. (1998) Specific genetic
predictors of chemotherapeutic response and survival in patients with
anaplastic oligodendrogliomas. J. Natl. Cancer Inst.
90,1473
-1479.
Cairncross, G., Swinnen, L., Bayer, R., Rosenfeld, S., Salzman, D., Paleologos, N., Kaminer, L., Forsyth, P., Stewart, D., Peterson, K., Hu, W., Macdonald, D., Ramsay, D., and Smith, A., for the Oligodendroglioma Study Group (2000) Myeloablative chemotherapy for recurrent aggressive oligodendroglioma Neuro-Oncology [serial online], Doc. 99-54, March 22, 2000. URL http://neuro-oncology.mc.duke.edu. Neuro-Oncology 2,114 -119.[Abstract]
Chinot, O.L., Jr., Honore, S., Barrie, M.F., Jr., Dufour, H., Braguer, D., and Grisoli, F. (2000) Temodal (Temozolomide, TMZ) in second line treatment after PCV in oligodendroglioma tumors.Pro. Am. Soc. Clin. Oncol. 19, 159. (Abstract)
Cobleigh, M.A., Vogel, C.L., Tripathy, D., Robert, N.J., Scholl,
S., Fehrenbacher, L., Wolter, J.M., Paton, V., Shak, S., Lieberman, G., and
Slamon D.J. (1999) Multinational study of the efficacy and safety
of humanized anti-HER2 monoclonal antibody in women who have
HER2-overexpressing metastatic breast cancer that has progressed after
chemotherapy for metastatic disease. J. Clin. Oncol.
17,2639
-2648.
Cormio, G., Gabriele, A., Maneo, A., Zanetta, G., Bonazzi, C., and Landoni, F. (1998) Complete remission of brain metastases from ovarian carcinoma with carboplatin. Eur. J. Obstet. Gynecol. Reprod. Biol. 78,91 -93.[CrossRef][Web of Science][Medline]
DeAngelis, L.M., Yahalom, J., Thaler, H.T., and Kher, U.
(1992) Combined modality therapy for primary CNS lymphoma.
J. Clin. Oncol. 10,635
-643.
DeAngelis, L.M., Burger, P.C., Green, S.B., and Cairncross, G.J. (1998) Malignant glioma: Who benefits from adjuvant chemotherapy? Ann. Neurol. 44,691 -695.[CrossRef][Web of Science][Medline]
Deininger, M.W., Vieira, S., Mendiola, R., Schultheis, B., Goldman,
J.M., and Melo, J.V. (2000) BCR-ABL tyrosine kinase activity
regulates the expression of multiple genes implicated in the pathogenesis of
chronic myeloid leukemia. Cancer Res.
60,2049
-2055.
Doolittle, N.D., Miner, M.E., Hall, W.A., Siegal, T., Hanson, E.J., Osztie, E., McAllister, L.D., Bubalo, J.S., Kraemer, D.F., Fortin, D., Nixon, R., Muldoon, L.L., and Neuwelt, E.A. (2000) Safety and efficacy of a multicenter study using intraarterial chemotherapy in conjunction with osmotic opening of the blood-brain barrier for the treatment of patients with maligant brain tumors. Cancer 88,637 -647.[CrossRef][Web of Science][Medline]
Doroshow, J.H. (1999) Pharmacological basis for high-dose chemotherapy. In: Thomas, E.D., Blume, K.G., and Forman, S.J. (Eds.), Hematopoietic Cell Transplantation. Second edition. Malden, Mass.: Blackwell Science. pp.103 -122.
Eck, S.L., Alavi, J.B., Alavi, A., Davis, A., Hackney, D., Judy K., Mollman, J., Phillips, P.C., Wheeldon, E.B., and Wilson, J.M. (1996) Treatment of advanced CNS malignancies with the recombinant adenovirus H5.010RSVTK: A phase I trial. Hum. Gene Ther. 7,1465 -1482.[Web of Science][Medline]
Eck, S.L., Alavi, J.B., Judy, K., Phillips, P., Alavi, A., Hackney, D., Cross, P., Hughes, J., Gao, G., Wilson, J.M. (2000) Treatment of recurrent or progressive malignant glioma with a recombinant adenovirus expressing human interferon-beta (H5.010CMVhIFN-ß): A phase I trial. Hum. Gene Ther. In press.
Fine, H.A., and Antman, K.H. (1992) High-dose chemotherapy with autologous bone marrow transplantation in the treatment of high grade astrocytomas in adults: Therapeutic rationale and clinical experience. Bone Marrow Transplant. 10,315 -321.[Web of Science][Medline]
Finlay, J.L., Goldman, S., Wong, M.C., Cairo, M., Garvin, J., August, C., Cohen, B.H., Stanley P., Zimmerman, R.A., Bostrom, B., Geyer, J.R., Harris, R.E., Sanders, J., Yates, A.J., Boyett, J.M., and Packer, R.J. (1996) Pilot study of high-dose thiotepa and etoposide phosphate with autologous bone marrow rescue in children and young adults with recurrent CNS tumors. J. Clin. Oncol. 14,2495 -2503.[Abstract]
Franciosi, V., Cocconi, G., Michiara, M., Di Costanzo, F., Fosser, V., Tonato, M., Carlini, P., Boni, C., and Di Sarra, S. (1999) Front-line chemotherapy with cisplatin and etoposide for patients with brain metastases from breast carcinoma, nonsmall cell lung carcinoma, or malignant melanoma: A prospective study. Cancer 85,1599 -1605.[CrossRef][Web of Science][Medline]
Giovagnoli, A.R., Tamburini, M., and Bioardi, A. (1996) Quality of life in brain tumor patients. J. Neurooncol. 30,71 -80.[Medline]
Glass, J., Gruber, M.L., Cher, L., and Hochberg, F.H. (1994) Preirradiation methotrexate chemotherapy of primary central nervous system lymphoma: Long-term outcome. J. Neurosurg. 81,188 -195.[Web of Science][Medline]
Graham, M.L., Herndon, J.E., II, Casey, J.R., Chaffee, S., Ciocci,
G.H., Krischer, J.P., Kurtzberg, J., Laughlin, M.J., Longee, D.C., Olson,
J.F., Paleologos, N., Pennington, C.N., and Friedman, H.S. (1997)
High-dose chemotherapy with autologous stem-cell rescue in patients with
recurrent high-risk pediatric brain tumors. J. Clin.
Oncol. 15,1814
-1823.
Gurtoo, H.L., Marinello, A.J., Berringan, M.J., Bansal, S.K., Paul, B., Pavelic, Z.P., and Struck, R.F. (1983) Effect of thiols on toxicity and carcinostatic activity of cyclophosphamide. Semin. Oncol. 10 (Suppl. 1),35 -45.[Web of Science][Medline]
Hryniuk, W.M., and Pater, J.L. (1987) Implications of dose intensity for cancer chemotherapy. Semin. Oncol. 14 (Suppl. 4),43 -44.[Web of Science][Medline]
Izquierdo, M., Martin, V., de Felipe, P., Izquierdo, J.M., Perez-Higueras, A., Cortes, M.L., Paz, J.F., Isla, A., and Blazquez, M.G. (1996) Human malignant brain tumor response to herpes simplex thymidine kinase (HSVtk)/ganciclovir gene therapy. Gene Ther. 3,491 -495.[Web of Science][Medline]
Izquierdo, M., Cortes, M.L., Martin, V., de Felipe, P., Izquierdo, J.M., Perez-Higueras, A., Paz, J.F., Isla, A., and Blazquez, M.G. (1997) Gene therapy in brain tumours: Implications of the size of glioblastoma on its curability. Acta Neurochir. Suppl. (Wien) 68,111 -117.[Medline]
Keldsen, N., Michalski, W., Bentzen, S.M., Hansen, K.B., and Thorling, K. (1996) Risk factors for central nervous system involvement in non-Hodgkinslymphoma—a multivariate analysis. Acta Oncol. 35,703 -708.[Web of Science][Medline]
Keshelava, N., Seeger, R.C., Groshen, S., and Reynolds, C.P.
(1998) Drug resistance patterns of human neuroblastoma cell lines
derived from patients at different phases of therapy. Cancer
Res. 58,5396
-5405.
Klatzmann, D., Valery, C.A., Bensimon, G., Marro, B., Boyer, O., Mokhtari, K., Diquet, B., Salzman, J.L., and Philippon, J. (1998) A Phase I/II study of herpes simplex virus type 1 thymidine kinase "suicide" gene therapy for recurrent glioblastoma. Hum. Gene Ther. 20,2595 -2604.
Lossos, A., Lossos, I.S., Bokstein, F., and Siegal, T. (1999) CNS involvement by systemic non-Hodgkin's lymphomas: Results of treatment with high dose methotrexate-based combination therapy. Neurology 52 (Suppl. 2),A281p . (Abstract)
Lovely, M.P. (1998) Quality of life in brain tumor patients. Semin. Oncol. Nurs. 14, 73-80.[CrossRef][Medline]
Martuza, R.L. (2000) Conditionally replicating herpes vectors for cancer therapy. J. Clin. Invest. 105,841 -846.[Web of Science][Medline]
Mason, W.P., Grovas, A., Halpern, S., Dunkel, I.J., Garvin, J.,
Heller, G., Rosenblum, M., Gardner, S., Lyden, D., Sands, S., Puccetti, D.,
Lindsley, K., Merchant, T.E., O'Malley, B., Bayer, L., Petriccione, M.M.,
Allen, J., and Finlay, J.L. (1998) Intensive chemotherapy and
bone marrow rescue for young children with newly diagnosed malignant brain
tumors. J. Clin. Oncol.
16,210
-221.
Matthay, K.K., Villablanca, J.G., Seeger, R.C., Stram, D.O.,
Harris, R.E., Ramsay, N.K., Swift, P., Shimada, H., Black, C.T., Brodeur,
G.M., Gerbing, R.B., and Reynolds, C.P. (1999) Treatment of
high-risk neuroblastoma with intensive chemotherapy, radiotherapy, autologous
bone marrow transplantation and 13-cis-retinoic acid. N. Engl. J.
Med. 341,1165
-1173.
McAllister, L.D., Doolittle, N.D., Guastadisegni, P.E., Kraemer, D.F., Lacy, C.A., Crossen, J.R., and Neuwelt, E.A. (2000) Cognitive outcomes and longterm follow-up results after enhanced chemotherapy delivery for primary central nervous system lymphoma. Neurosurgery 46,51 -61.[CrossRef][Web of Science][Medline]
Morra, E., Lazzarino, M., Brusamolino, E., Pagnucco, G., Castagnola, C., Bernasconi, P., Orlandi, E., Corso, A., Santagostino, A., and Bernasconi, C., (1993) The role of systemic high-dose cytarabine in the treatment of central nervous system leukemia: Clinical results in 46 patients. Cancer 72,439 -445.[CrossRef][Web of Science][Medline]
Muldoon, L.L., Pagel, M.A., Kroll, R.A., Brummett, R.E., Doolittle,
N.D., Zuhowski, E.G., Egorin, M.J., and Neuwelt, E.A. (2000)
Delayed administration of sodium thiosulfate in animal models reduces platinum
ototoxicity without reduction of antitumor activity. Clin. Cancer
Res. 6,309
-315.
Nelson, D.F., Martz, K.L., Bonner, H., Nelson, J.S., Newall, J., Kerman, H.D., Thompson, J.W., and Murray, K.J. (1992) Non-Hodgkin's lymphoma of the brain: can high dose, large volume radiation therapy improve survival? Report on a prospective trial by the Radiation Therapy Oncology Group (RTOG): RTOG 8315. Int. J. Radiat. Oncol. Biol. Phys. 23,9 -17.[Web of Science][Medline]
Neuwelt, E.A., Muldoon, L.L., Pagel, M.A., Walker, S., and Hasler, B. (2000) Enhancing CNS chemotherapy cytotoxicity using BSO with systemic thiol chemoprotection against myelosuppression. Neuro-Oncology 2,283 . (Abstract 152)
O'Neill, B.P., Wang, C.H., O'Fallon, J.R., Colgan, J.D., Earle, J.D., Krigel, R.L., Brown, L.D., and McGinnis, W.L. (1999) Primary central nervous system non-Hodgkin's lymphoma (PCNSL): Survival advantages with combined initial therapy? A final report of the North Central Cancer Treatment Group (NCCTG) Study 86-72-52. Int. J. Radiat. Oncol. Biol. Phys. 43,559 -563.[CrossRef][Web of Science][Medline]
Paleologos, N.A., MacDonald, D.R., Vick N.A., and Cairncross, J.G.
(1999) Neoadjuvant procarbazine, CCNU, and vincristine for
anaplastic and aggressive oligodendroglioma. Neurology
53,1141
-1143.
Ram, Z., Culver, K.W., Oshiro, E.M., Viola, J.J., DeVroom, H.L., Otto, E., Long, Z., Chiang, Y., McGarrity, G.J., Muul, L.M., Katz, D., Blaese, R.M., and Oldfield, E.H. (1997) Therapy of maliganant brain tumors by intratumoral implantation of retroviral vector-producing cells. Nat. Med. 3,1354 -1361.[CrossRef][Web of Science][Medline]
Shand, N., Weber, F., Mariani, L., Bernstein, M., Gianella-Borradori, A., Long, Z., Sorensen, A.G., and Barbier, N. (1999) A Phase I/II clinical trial of gene therapy for recurrent glioblastoma multiforme by tumor transduction with the herpes simplex thymidine kinase gene followed by ganciclovir. Hum. Gene Ther. 10,2325 -2335.[CrossRef][Web of Science][Medline]
Siegal, T. (1998) Leptomeningeal metastases: Rationale for systemic chemotherapy or what is the role of intra-CSF-chemotherapy? J. Neurooncol. 38,151 -157.[CrossRef][Medline]
Siegal, T., Lossos, A., and Pfeffer, M.R. (1994)
Leptomeningeal metastases: Analysis of 31 patients with sustained off-therapy
response following combined-modality therapy.
Neurology 44,1463
-1469.
Stadtmauer, E.A., O'Neill, A., Goldstein, L.J., Crilley, P.A.,
Mangan, K.F., Ingle, J.N., Brodsky, I., Martino, S., Lazarus, H.M., Erban,
J.K., Sickles, C., and Glick, J.H. (2000) Conventional-dose
chemotherapy compared with high-dose chemotherapy plus autologous
hematopoietic stem-cell transplantation for metastatic breast cancer:
Philadelphia Bone Marrow Transplant Group. N. Engl. J.
Med. 342,1069
-1076.
Trask, T.W., Trask, R.P., Aguilat-Cordova, E., Shine, D.H., Wyde, P.R., Goodman, J.C., Hamilton, W.J., Rojas-Martinez, A., Chen, S.H., Woo, S.L.C., and Grossman, R.G. (2000) Phase I study of adenoviral delivery of the HSV-tk gene and ganciclovir administration in patients with recurrent malignant brain tumors. Mol. Ther. 1, 195-203.[CrossRef][Web of Science][Medline]
van Besien, K., Ha, C.S., Murphy, S., McLaughlin, P., Rodriguez,
A., Amin, K., Forman, A., Romaguera, J., Hagemeister, F., Younes, A., Bachier,
C., Sarris, A., Sobocinski, K.S., Cox, J.D., and Cabanillas, F.
(1998) Risk factors, treatment, and outcome of central nervous
sytem recurrence in adults with intermediate-grade and immunoblastic lymphoma.
Blood 91,1178
-1184.
Walker, M.D., Green, S.B., Byar, D.P., Alexander, E., Jr., Batzdorf, U., Brooks, W.H., Hunt, W.E., MacCarty, C.S., Mahaley, M.S., Mealey, J., Jr., Owens, G., Ransohoff, J., II, Robertson, J.T., Shapiro, W.R., Smith, K.B., Jr., Wilson, C.B., and Strike, T.A. (1980) Randomized comparisons of radiotherapy and nitrosoureas for the treatment of malignant glioma after surgery. N. Engl. J. Med. 303,1323 -1329.[Abstract]
Wolf, M.M., Olver, I.N., Ding, J.C., Cooper, I.A., Liew, K.H., and Madigan, J.P. (1985) Non-Hodgkin's lymphoma involving the central nervous system. Aust. N. Z. J. Med. 15, 16-21.[Web of Science][Medline]
Yung, W.K., Prados, M.D., Yaya-Tur, R., Rosenfeld, S.S., Brada, M.,
Freidman, H.S., Albright, R., Olson, J., Chang, S.M., O'Neill, A.M., Friedman,
A.H., Bruner, J., Yue, N., Dugan, M., Zaknoen, S., and Levin, V.A.
(1999) Multicenter phase II trial of temozolomide in patients
with anaplastic astrocytoma or anaplastic oligoastrocytoma at first relapse.
J. Clin. Oncol. 17,2762
-2771.
CiteULike 
Connotea 
Del.icio.us 
Digg 
Reddit 
Technorati What's this?
This article has been cited by other articles:
|
|
 |
|
  M. A. Askins and B. D. Moore III Preventing Neurocognitive Late Effects in Childhood Cancer Survivors J Child Neurol, October 1, 2008; 23(10): 1160 - 1171. [Abstract] [PDF]
|
|
|
|
 |
|
 B. D. Moore III Neurocognitive Outcomes in Survivors of Childhood Cancer J. Pediatr. Psychol., January 1, 2005; 30(1): 51 - 63. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 N. D. Doolittle, L. E. Abrey, N. Ferrari, W. A. Hall, E. R. Laws, R. E. McLendon, L. L. Muldoon, D. Peereboom, D. R. Peterson, C. P. Reynolds, et al. Targeted Delivery in Primary and Metastatic Brain Tumors: Summary Report of the Seventh Annual Meeting of the Blood-Brain Barrier Disruption Consortium Clin. Cancer Res., June 1, 2002; 8(6): 1702 - 1709. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 E. A. Neuwelt, M. A. Pagel, B. P. Hasler, T. G. Deloughery, and L. L. Muldoon Therapeutic Efficacy of Aortic Administration of N-Acetylcysteine as a Chemoprotectant against Bone Marrow Toxicity after Intracarotid Administration of Alkylators, with or without Glutathione Depletion in a Rat Model Cancer Res., November 1, 2001; 61(21): 7868 - 7874. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 L. L. Muldoon, S. L. Walker-Rosenfeld, C. Hale, S. E. Purcell, L. C. Bennett, and E. A. Neuwelt Rescue from Enhanced Alkylator-Induced Cell Death with Low Molecular Weight Sulfur-Containing Chemoprotectants J. Pharmacol. Exp. Ther., March 1, 2001; 296(3): 797 - 805. [Abstract] [Full Text]
|
|
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|
|
