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Clinical Investigations |
Centre for Developmental Cancer Therapeutics, Parkville, Victoria, affiliates: Department of Clinical Haematology and Medical Oncology, Royal Melbourne Hospital, Parkville, Victoria 3050 (S.L.C., M.A.R., S.S.W., A.W.); Department of Medical Oncology, Royal Children's Hospital, Parkville, Victoria 3050 (D.M.A.); Department of Medical Oncology, St. Vincent's Hospital, Fitzroy, Victoria 3065 (A.D.); and Department of Medical Oncology, Austin and Repatriation Medical Centre, Heidelberg, Victoria 3184 (L.M.C.); Australia
1 Address correspondence to Mark Rosenthal, Department of Clinical Haematology and Medical Oncology, Royal Melbourne Hospital, Parkville, Victoria 3050, Australia (mark.rosenthal{at}mh.org.au).
Abstract
Temozolomide has established activity in the treatment of recurrent glioblastoma multiforme (GBM). Caelyx (liposomal doxorubicin) has established activity in a broad range of tumors but has not been extensively evaluated in the treatment of GBM. Phase 1 data suggest that temozolomide and Caelyx can be combined safely at full dose. In this phase 2 study, combination temozolomide (200 mg/m2 orally, days 1-5) and Caelyx (40 mg/m2 i.v., day 1) was given every 4 weeks to a cohort of 22 patients with recurrent GBM, who received a total of 109 cycles (median 3.5 cycles). The median age of the patients was 55 years (range, 31-80 years), and 17 were male. All patients had received radiotherapy, but only 2 had received prior chemotherapy. One patient (5%) had a complete response, 3 patients (14%) had a partial response, and 11 patients (50%) had stable disease. The median time to progression for the cohort was 3.2 months (range, 1-13 months). Median overall survival was 8.2 months (range, 1-16+ months). Seven patients (32%) were progression free at 6 months. Hematological toxicity included grade 3/4 neutropenia in 4 patients (18%) and grade 3/4 thrombocytopenia in 4 patients (18%). Grade 3 nonhematologic toxicity included rash in 3 patients (14%), nausea and vomiting in 1 patient (4%), hypersensitivity reaction to Caelyx in 3 patients (14%), and palmar-plantar toxicity in 1 patient (4%). We conclude that the combination of temozolomide and Caelyx is well tolerated, results in a modest objective response rate, but has encouraging disease stabilization in the treatment of recurrent GBM.
References
Brada, M., Hoang-Xuang, K., Rampling, R., Dietrich, P.-Y., Dirix,
L.Y., Macdonald, D., Heimans, J.J., Zonnenberg, B.A., Bravo-Marques, J.M.,
Henriksson, R., Stupp, R., Yue, N., Bruner, J., Dugan, M., Rao, S., and
Zaknoen, S. (2001) Multicentre phase II trial of temozolomide in
patients with glioblastoma multiforme at first relapse. Ann.
Oncol. 12,259
-266.
Britten, C.D., Rowinsky, E.K., Baker, S.D., Agarwala, S.S.,
Eckardt, J.R., Bar rington, R., Diab, S.G., Hammond, L.A., Johnson, T.,
Villalona-Calero, M., Fraass, U., Statkevich, P., Von Hoff, D.D., and
Eckhardt, S.G. (1999) A Phase I and pharmacokinetic study of
temozolomide and cisplatin in patients with advanced solid malignancies.
Clin. Cancer Res. 5,1629
-1637.
Burton, E., and Prados, M. (1999) New chemotherapy options for the treatment of malignant gliomas. Curr. Opin. Oncol. 11,157 -161.[CrossRef][Medline]
Clarke, K., Basser, R.L., Underhill, C., Mitchell, P., Bartlett,
J., Cher, L., Findlay, M., Dalley, D., Pell, M., Byrne, M., Geldard, H., Hill,
J.S., Maher, D., Fox, R.M., Green, M.D., and Kaye, A.H. (1999)
KRN8602 (MX2-hydochloride): An active new agent for the treatment of recurrent
high-grade glioma. J. Clin. Oncol.
17,2579
-2584.
Fabel, K., Dietrich, J., Hau, P., Wismeth, C., Winner, B., Przywara, S., Stein brecher, A., Ullrich, W., Bogdahn, U. (2001) Long-term stabilization in patients with malignant glioma after treatment with liposomal doxoru bicin. Cancer 92,1936 -1942.[CrossRef][ISI][Medline]
Friedman, H.S., Kerby, T., and Calvert, H. (2000)
Temozolomide and treatment of malignant glioma. Clin. Cancer
Res. 6,2585
-2597.
Gander, M., Leyvraz, S., Decosterd, L., Bonfanti, M., Marzolini,
C., Shen, F., Lienard, D., Perey, L., Colella, G., Biollaz, J., Lejeune, F.,
Yarosh, D., Belanich, M., and D'Incalci, M. (1999) Sequential
administration of temozolomide and fotemustine: Depletion of O6-alkyl
guanine-DNA transferase in blood lymphocytes and in tumours. Ann.
Oncol. 10,831
-838.
Gilbert, M.R. (2001) Neuro-oncology clinical trials:
Promise and pitfalls. Ann. Oncol.
12,149
-150.
Harris, M.T., Rosenthal, M.A., Ashley, D.L., and Cher, L. (2001) An Aus tralian experience with temozolomide for the treatment of recurrent high grade glioma. J. Clin. Neurosci. 8,325 -327.[CrossRef][ISI][Medline]
Jemal, A., Thomas, A., Murray, T., and Thun, M. (2002)
Cancer statistics, 2002. CA Cancer J. Clin.
52, 23-47.
Kappelle, A.C., Postma, T.J., Taphoorn, M.J.B., Groeneveld, G.J.,
van den Bent, M.J., van Groeningen, C.J., Zonnenberg, B.A., Sneeuw, K.C.A.,
and Heimans, J.J. (2001) PCV chemotherapy for recurrent
glioblastoma multiforme. Neurology
56,118
-120.
Khan, R.B., Raizer, J.J., Malkin, M.G., Bazylewicz, K.A., and
Abrey, L.E. (2002) A phase II study of extended low-dose
temozolomide in recurrent malignant gliomas.
Neuro-Oncology 4,39
-43.
Koukourakis, M.I., Koukouraki, S., Fezoulidis, I., Kelekis, N., Kyrias, G., Archimandritis, S., and Karkavitsas, N. (2000) High intratumoural accu mulation of Stealth liposomal doxorubicin (Caelyx) in glioblastomas and in metastatic brain tumours. Br. J. Cancer 83,1281 -1286.[CrossRef][ISI][Medline]
Levin, V.A. (1999) Chemotherapy for brain tumors of astrocytic and oligodendroglial lineage: The past decade and where we are heading. Neuro-Oncol. 1,69 -80.[Abstract]
MacDonald, D.R., Cascino, T.L., Schold, S.C., Jr., and Cairncross, J.G. (1994) Response criteria for phase II studies of supratentorial malignant gliomas. J. Clin. Oncol. 8,1277 -1280.
NCI. National Cancer Institute (1999) Common Toxicity Criteria version 2.0. Available at https://webapps.ctep.nci.nih.gov/ctcv2/plsql/ctc000w$.startup.
Patel, V.J., Elion, G.B., Houghton, P.J., Keir, S., Pegg, A.E.,
Johnson, S.P., Dolan, M.E., Bigner, D.D., and Friedman, H.S.
(2000) Schedule-dependent activity of temozolomide plus CPT-11
against a human central nervous system tumor-derived xenograft.
Clin. Cancer Res. 6,4154
-4157.
Rosenthal, M.A., Gruber, M.L., Glass, J., Nirenberg, A., Finlay, J., Hochster, H., and Muggia, F.M. (2000) Phase II study of combination taxol and estramustine phosphate in the treatment of recurrent glioblastoma mul tiforme. J. Neurooncol. 47, 59-63.[CrossRef][Medline]
Sharma, U.S., Sharma, A., Chau, R.I., and Straubinger, R.M. (1997) Liposome-mediated therapy of intracranial brain tumors in a rat model. Pharm. Res. 14,992 -998.[CrossRef][ISI][Medline]
Siegal, T., Horowitz, A., and Gabizon A. (1995) Doxorubicin encapsulated in sterically stabilized liposomes for the treatment of a brain tumor model: Biodistribution and therapeutic efficacy. J. Neurosurg. 83,1029 -1037.[ISI][Medline]
Simon, R. (1989) Optimal two-stage designs for phase II clinical trials. Con trol. Clin. Trials 10, 1-10.
Stupp, R., Gander, M., Leyvraz, S., and Newlands, E. (2001) Current and future developments in the use of temozolomide for the treatment of brain tumours. Lancet Oncol. 2, 552-560.[CrossRef][ISI][Medline]
Surawicz, T.S., McCarthy, B.J., Kupelian, V., Jukich, P.J., Bruner, J.M., and Davis, F.G. (1999) Descriptive epidemiology of primary brain and CNS tumors: Results from the Central Brain Tumor Registry of the United States, 1990-1994. Neuro-Oncol. 1, 14-25.[Abstract]
Uziely, B., Jeffers, S., Isacson, R., Kutsch, K., Wei-Tsao, D., Yehoshua, Z., Lib son, E., Muggia, F.M., and Gabizon, A. (1995) Liposomal doxorubicin: Antitumor activity and unique toxicities during two complementary phase I studies. J. Clin. Oncol. 13,1777 -1785.
Volm, M., Oratz, R., Pavlick, A., Farrell, K., Lee, J., and Muggia, F. (2000) A phase I study of liposomal doxorubicin and temozolomide in patients with advanced cancer. Proc. Am. Soc. Clin. Oncol. 19,223a (abstract 872).
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., Jr., Mealey, J., Jr., Owens, G., Ransohoff, J., 2nd, Robertson, J.T., Shapiro, W.R., Smith, K.R., 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]
Wong, E.T., Hess, K.R, Gleason, M.I., Jaeckle, K.A., Kyritsis,
A.P., Prados, M.D., Levin, V.A., and Yung, W.K.A. (1999) Outcomes
and prognostic factors in recurrent glioma patients enrolled onto phase II
clinical trials. J. Clin. Oncol.
17, 2572
(comment).
Yung, W.K.A, Albright, R.E., Olson, J., Fredericks, R., Fink, K., Prados, M.D., Brada, M., Spence, A., Hohl, R.J., Shapiro, W., Glantz, M., Greenberg, H., Selker, R.G., Vick, N.A., Rampling, R., Friedman, H., Phillips, P., Bruner, J., Yue, N., Osoba, D., Zaknoen, S., and Levin, V.A. (2000) A phase II study of temozolomide vs. procarbazine in patients with glioblastoma multiforme at first relapse. Br. J. Can. 83,588 -593.[CrossRef][ISI][Medline]
Yung, W.K.A., Prados, M.D., Yaya-Tur, R., Rosenfeld, S.S., Brada,
M., Fried man, H.S., Albright, R., Olson, J., Chang, S.M., O'Neil, 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.
Temodal Brain Tumor Group. J. Clin. Oncol.
17,2762
-2771.
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