|
|
|
|
|
|
||
|
|
||||
|
|
||||
|
||||
Clinical Therapy Trials—Outcomes |
Departments of Neuro-Oncology (E.T.W., K.A.J., A.P.K., V.A.L., W.K.A.Y.) and Biomathematics (K.R.H.), The University of Texas M.D. Anderson Cancer Center, Houston, TX 77030; and the Department of Neurological Surgery, University of California, San Francisco, CA 94143 (M.D.P.)
2 Address correspondence and reprint requests to Kenneth R. Hess, Ph.D., Department of Biomathematics, Box 237, The University of Texas M.D. Anderson Cancer Center, 1515 Holcombe Boulevard, Houston, TX 77030.
Abstract
In this article we report the results of a study of the relationship between response and progression in 375 patients with recurrent glioma enrolled in phase II chemotherapy trials. We reviewed the records of patients from 8 consecutive phase II trials, including 225 patients with recurrent glioblastoma multiforme and 150 with recurrent anaplastic astrocytoma. Median age was 45 years (range, 15–82) and median Karnofsky performance score was 80 (range, 60–100). Forty-one patients (11%) had more than two prior resections and/or more than two prior chemotherapy regimens. Best response was complete (n = 1) or partial (n = 33) in 34 patients (9%). Median time to response was 14 weeks, and median response duration was 44 weeks. Simon-Makuch estimates for 52-week progression-free survival for patients progression-free at 13 weeks were 48% for response and 28% for nonresponse. When response was treated as a time-dependent covariate in a Cox proportional hazards regression analysis, response was associated with significantly lower failure rates (hazard ratio 0.5; 95% confidence interval 0.3–0.8; P = 0.0016). This study showed that response in recurrent glioma is associated with a significant reduction in progression rates.
References
A'Hern, R.P., Ebbs, S.R., and Baum M.B. (1988) Does chemotherapy improve survival in advanced breast cancer? A statistical overview. Br. J. Cancer 57,615 -618.[ISI][Medline]
Anderson, J.R., Cain, K.C., and Gelber, R.D. (1983) Analysis of survival by tumor response. J. Clin. Oncol. 1,710 -719.[Abstract]
Anderson, J.R., Cain, K.C., Gelber, R.D., and Gelman, R.S. (1985) Analysis and interpretation of the comparison of survival by treatment outcome variables in cancer clinical trials. Cancer Treat. Rep. 69,1139 -1146.[ISI][Medline]
Bull, K., and Spiegelhalter, D.J. (1997) Survival analysis in observational studies. Stat. Med. 16,1041 -1074.[CrossRef][ISI][Medline]
Buyse, M., and Piedbois, P. (1996) On the relationship between response to treatment and survival time. Stat. Med. 15,2797 -2812.[CrossRef][ISI][Medline]
Cnaan, A., and Ryan, L. (1989) Survival analysis in natural history studies of disease. Stat. Med. 8,1255 -1268.[ISI][Medline]
Cox, D.R. (1972) Regression models and life tables (with discussion). J. Royal Stat. Soc. B 74,187 -220.
Eagan, R.T., and Scott, M. (1983) Evaluation of prognostic factors in chemotherapy of recurrent brain tumors. J. Clin. Oncol. 1,38 -44.[Abstract]
Feuer, E.J., Hankey, B.F., Gaynor, J.J., Wesley, M.N., Baker, S.G., and Meyer, J.S. (1992) Graphical representation of survival curves associated with a binary non-reversible time dependent covariate. Stat. Med. 11,455 -474.[ISI][Medline]
Fine, H.A. (1994) The basis for current treatment recommendations for malignant gliomas. J. Neurooncol. 20,111 -120.[CrossRef][Medline]
Graf, W., Pahlman, L., Bergstrom, R., and Glimelius, B. (1994) The relationship between an objective response to chemotherapy and survival in advanced colorectal cancer. Br. J. Cancer 70,559 -563.[ISI][Medline]
Grambsch, P.M., and Therneau, T.M. (1994) Proportional
hazards tests and diagnostics based on weighted residuals.
Biometrika 81,515
-526.
Grant, R., Liang, B.C., Slattery, J., Greenberg, H.S., and Junck, L. (1997) Chemotherapy response criteria in malignant glioma. Neurology 48,1336 -1340.[Abstract]
Hess, K.R. (1995) Graphical methods for assessing violations of the proportional hazards assumptions in Cox regression. Stat. Med. 14,1707 -1723.[ISI][Medline]
Kaplan, E.L., and Meier, P. (1958) Nonparametric estimation from incomplete observations. J. Am. Stat. Assoc. 53,457 -481.[CrossRef][ISI]
Klein, J.P., and Moeschberger, M.L. (1997) Survival Analysis: Techniques for Censored and Truncated Data. New York: Springer. pp. 153, 271, 276.
Leventhal, B.G., and Wittes, R.E. (1988) Research Methods in Clinical Oncology. New York: Raven Press. pp. 69-70.
Macdonald, D.R., Cascino, T.L., Schold, S.C., Jr., and Cairncross, J.G. (1990) Response criteria for phase II studies of supratentorial malignant glioma. J. Clin. Oncol. 8,1277 -1280.[Abstract]
Pepe, M.S., and Cai, J. (1993) Some graphical displays and marginal regression analyses for recurrent failure times and time dependent covariates (in theory and methods). J. Am. Stat. Assoc. 88,811 -820.[CrossRef][ISI]
Perry, J.R., DeAngelis, L.M., Schold, S.C., Jr., Burger, P.C.,
Brem, H., Brown, M.T., Curran, W.J., Scott, C.B., Prados, M.D., Kaplan, R.,
and Cairncross, J.G. (1997) Challenges in the design and conduct
of phase III brain tumor therapy trials. Neurology
49,912
-917.
Rajan, B., Ross, G., Lim, C.C., Ashley, S., Goode, D., Traish, D., and Brada, M. (1994) Survival in patients with recurrent glioma as a measure of treatment efficacy: Prognostic factors following nitrosourea chemotherapy. Eur. J. Cancer 30A,1809 -1815.[CrossRef]
Simon, R., and Makuch, R.W. (1984) A non-parametric graphical representation of the relationship between survival and the occurrence of an event: Application to responder versus non-responder bias. Statis. Med. 3,35 -44.
Slack, N.H., Mittelman, A., Brady, M.F., and Murphy, G.P. (1980) The importance of the stable category for chemotherapy treated patients with advanced and relapsing prostate cancer. Cancer 46,2393 -2402.[CrossRef][ISI][Medline]
Torri, V., Simon, R., Russek-Cohen, E., Midthune, D., and Friedman,
M. (1992) Statistical model to determine the relationship of
response and survival in patients with advanced ovarian cancer treated with
chemotherapy. J. Natl. Cancer Inst.
84,407
-414.
Wand, M.P., and Jones, M.C. (1997) Kernel Smoothing. Second edition. New York: Chapman and Hall.
Weiss, G.B., Bunce, H., III, and Hokanson, J.A. (1983) Comparing survival of responders and nonresponders after treatment: A potential source of confusion in interpreting cancer clinical trials. Control. Clin. Trials 4,43 -52.[CrossRef][ISI][Medline]
Wong, E.T., Hess, K.R., Gleason, M.J., 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 in phase II
clinical trials. J. Clin. Oncol.
17,2572
-2578.
This article has been cited by other articles:
|
|
 |
|
  S. M. Chang, K. R. Lamborn, J. G. Kuhn, W.K. A. Yung, M. R. Gilbert, P. Y. Wen, H. A. Fine, M. P. Mehta, L. M. DeAngelis, F. S. Lieberman, et al. Neurooncology clinical trial design for targeted therapies: Lessons learned from the North American Brain Tumor Consortium Neuro-oncol, August 1, 2008; 10(4): 631 - 642. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 D. A. Hamstra, C. J. Galban, C. R. Meyer, T. D. Johnson, P. C. Sundgren, C. Tsien, T. S. Lawrence, L. Junck, D. J. Ross, A. Rehemtulla, et al. Functional Diffusion Map As an Early Imaging Biomarker for High-Grade Glioma: Correlation With Conventional Radiologic Response and Overall Survival J. Clin. Oncol., July 10, 2008; 26(20): 3387 - 3394. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J.W. Henson, S. Ulmer, and G.J. Harris Brain Tumor Imaging in Clinical Trials AJNR Am. J. Neuroradiol., March 1, 2008; 29(3): 419 - 424. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. E. Loghin, M. D. Prados, P. Wen, L. Junck, F. Lieberman, H. Fine, K. L. Fink, M. Metha, J. Kuhn, K. Lamborn, et al. Phase I Study of Temozolomide and Irinotecan for Recurrent Malignant Gliomas in Patients Receiving Enzyme-Inducing Antiepileptic Drugs: A North American Brain Tumor Consortium Study Clin. Cancer Res., December 1, 2007; 13(23): 7133 - 7138. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
E. T. Wong and S. Brem Taming Glioblastoma: Targeting Angiogenesis J. Clin. Oncol., October 20, 2007; 25(30): 4705 - 4706. [Full Text] [PDF]
|
|
|
|
|
|
K. V. Ballman, J. C. Buckner, P. D. Brown, C. Giannini, P. J. Flynn, B. R. LaPlant, and K. A. Jaeckle The relationship between six-month progression-free survival and 12-month overall survival end points for phase II trials in patients with glioblastoma multiforme Neuro-oncol, January 1, 2007; 9(1): 29 - 38. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 W A Tome and S P Howard On the possible increase in local tumour control probability for gliomas exhibiting low dose hyper-radiosensitivity using a pulsed schedule Br. J. Radiol., January 1, 2007; 80(949): 32 - 37. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
E. Galanis, J. C. Buckner, M. J. Maurer, R. Sykora, R. Castillo, K. V. Ballman, B. J. Erickson, and for the North central cancer treatment Group Validation of neuroradiologic response assessment in gliomas: Measurement by RECIST, two-dimensional, computer-assisted tumor area, and computer-assisted tumor volume methods Neuro-oncol, April 1, 2006; 8(2): 156 - 165. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. D. Prados, K. Lamborn, W.K.A. Yung, K. Jaeckle, H. I. Robins, M. Mehta, H. A. Fine, P. Y. Wen, T. Cloughesy, S. Chang, et al. A phase 2 trial of irinotecan (CPT-11) in patients with recurrent malignant glioma: A North American Brain Tumor Consortium study Neuro-oncol, April 1, 2006; 8(2): 189 - 193. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 D. A. Hamstra, T. L. Chenevert, B. A. Moffat, T. D. Johnson, C. R. Meyer, S. K. Mukherji, D. J. Quint, S. S. Gebarski, X. Fan, C. I. Tsien, et al. Evaluation of the functional diffusion map as an early biomarker of time-to-progression and overall survival in high-grade glioma PNAS, November 15, 2005; 102(46): 16759 - 16764. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. M. Chang, S. L. Reynolds, N. Butowski, K. R. Lamborn, J. C. Buckner, R. S. Kaplan, and D. D. Bigner GNOSIS: Guidelines for neuro-oncology: Standards for investigational studies--reporting of phase 1 and phase 2 clinical trials Neuro-oncol, October 1, 2005; 7(4): 425 - 434. [Abstract] [PDF]
|
|
|
|
|
|
T. F. Cloughesy, J. Kuhn, H. I. Robins, L. Abrey, P. Wen, K. Fink, F. S. Lieberman, M. Mehta, S. Chang, A. Yung, et al. Phase I Trial of Tipifarnib in Patients With Recurrent Malignant Glioma Taking Enzyme-Inducing Antiepileptic Drugs: A North American Brain Tumor Consortium Study J. Clin. Oncol., September 20, 2005; 23(27): 6647 - 6656. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
E. Galanis, J. C. Buckner, M. J. Maurer, J. I. Kreisberg, K. Ballman, J. Boni, J. M. Peralba, R. B. Jenkins, S. R. Dakhil, R. F. Morton, et al. Phase II Trial of Temsirolimus (CCI-779) in Recurrent Glioblastoma Multiforme: A North Central Cancer Treatment Group Study J. Clin. Oncol., August 10, 2005; 23(23): 5294 - 5304. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. D. Prados, W.K.A. Yung, K. A. Jaeckle, H. I. Robins, M. P. Mehta, H. A. Fine, P. Y. Wen, T. F. Cloughesy, S. M. Chang, M. K. Nicholas, et al. Phase 1 trial of irinotecan (CPT-11) in patients with recurrent malignant glioma: A North American Brain Tumor Consortium study Neuro-oncol, January 1, 2004; 6(1): 44 - 54. [Abstract] [PDF]
|
|
|
|
|
|
C. A. Meyers and K. R. Hess Multifaceted end points in brain tumor clinical trials: Cognitive deterioration precedes MRI progression Neuro-oncol, April 1, 2003; 5(2): 89 - 95. [Abstract] [PDF]
|
|
|
|
|
|
F. F. Lang, M. R. Gilbert, V. K. Puduvalli, J. Weinberg, V. A. Levin, W.K. A. Yung, R. Sawaya, G. N. Fuller, and C. A. Conrad Toward better early-phase brain tumor clinical trials: A reappraisal of current methods and proposals for future strategies Neuro-oncol, October 1, 2002; 4(4): 268 - 277. [Abstract] [PDF]
|
|
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|
|
