Journal of Clinical Oncology, Vol 21, Issue 13
(July), 2003: 2525-2528
© 2003 American Society for Clinical Oncology
Phase II Study of First-Line Chemotherapy With Temozolomide in Recurrent Oligodendroglial Tumors: The European Organization for Research and Treatment of Cancer Brain Tumor Group Study 26971
M.J. van den Bent,
M.J.B. Taphoorn,
A.A. Brandes,
J. Menten,
R. Stupp,
M. Frenay,
O. Chinot,
J.M. Kros,
C.C.D. van der Rijt,
Ch.J. Vecht,
A. Allgeier,
T. Gorlia
From the Departments of Neuro-Oncology, Pathology, and Medical Oncology, University Hospital Rotterdam/Rotterdam Cancer Center, Rotterdam; Department of Neurology, University Medical Center Utrecht, Utrecht; and Department of Neurology, Medical Center Haaglanden/Westeinde, the Hague, the Netherlands; Medical Oncology Department, University Hospital, Padova, Italy; Department of Radiotherapy-Oncology, Univeersitair Ziekenhuis Gasthuisberg, Leuven; European Organization for Research and Treatment of Cancer DataCenter, Brussels, Belgium; Department of Medical Oncology, Centre Hospitalier Universitaire Vaudois, Lausanne, Switzerland; Centre Antoine Lacassagne, Nice; and Hôpital la Timone, Marseille, France.
Address reprint requests to M.J. van den Bent, Department of Neuro-Oncology, University Hospital Rotterdam/Rotterdam Cancer Center, PO Box 5201, 3008 AE Rotterdam, the Netherlands; email: m.vandenbent{at}erasmusmc.nl.
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ABSTRACT
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Purpose: Oligodendroglial tumors are chemotherapy-sensitive tumors, with two thirds of patients responding to combination chemotherapy with procarbazine, lomustine, and vincristine (PCV). Temozolomide (TMZ), a new alkylating and methylating agent, has demonstrated high response rates in patients with recurrent anaplastic astrocytoma. We investigated TMZ as first-line chemotherapy in recurrent oligodendroglial tumors (OD) and mixed oligoastrocytomas (OA) after surgery and radiation therapy.
Patients and Methods: In a prospective, nonrandomized, multicenter, phase II trial, patients were treated with 200 mg/m2 of TMZ on days 1 through 5 in 28-day cycles for 12 cycles. Patients with a recurrence after prior surgery and radiotherapy, and with measurable and enhancing disease on magnetic resonance imaging (MRI) were eligible for this study. Patients with large lesions and mass effect or with new clinical deficits were not eligible. Pathology and the MRI scans of all responding patients were centrally reviewed.
Results: Thirty-eight eligible patients were included. In three patients, pathology review did not confirm the presence of an OD or OA. TMZ was generally well tolerated. The most frequent side effects were hematologic; only one patient discontinued treatment for toxicity. In 20 (52.6%) of 38 patients (95% exact confidence interval, 35.8% to 69.0%), a complete (n = 10) or partial response to TMZ was observed. The median time to progression was 10.4 months for all patients and 13.2 months for responding patients. At 12 months from the start of treatment, 40% of patients were still free from progression.
Conclusion: TMZ provides an excellent response rate with good tolerability in chemotherapy-naive patients with recurrent OD. A randomized phase III study comparing PCV with TMZ is warranted.
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INTRODUCTION
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OLIGODENDROGLIOMAS (OD) ARE chemotherapy-sensitive gliomas, with 60% to 70% of patients responding to chemotherapy with procarbazine, lomustine, and vincristine (PCV) and a median time to progression (TTP) for responding patients of 12 to 18 months.1–4 Although PCV in general is considered well tolerated, lomustine induces a cumulative myelosuppression that frequently requires dose reductions and delays and discontinuation of treatment before the intended number of six cycles is reached. Nausea, weight loss, and fatigue are other side effects of the PCV schedule that limit treatment in a significant number of patients. New active agents and treatment regimens with less negative effects on the quality of life would therefore be a major improvement for the treatment of these patients.
Temozolomide (TMZ) is a new oral alkylating and methylating agent that has demonstrated good tolerance and promising activity in astrocytic tumors. In a large study of 162 patients with recurrent anaplastic astrocytoma treated in first or second line with TMZ, an objective response rate of 35% was achieved.5 Furthermore, stabilized and responding patients showed improved quality of life.6 Because of these results, we initiated two European Organization for Research and Treatment of Cancer (EORTC) studies in recurrent OD after radiation therapy, one investigating TMZ as first-line and the other as second-line chemotherapy. We present here the results of the EORTC Study 26971 on first-line chemotherapy with TMZ. Because patients with recurrent OD had standard treatment options (PCV chemotherapy), patients with large lesions and mass effect or progressive neurologic deficits were not considered eligible for this study.
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PATIENTS AND METHODS
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Patients were eligible if they had (1) histologically proven OD or mixed oligoastrocytomas (OA) provided that 25% of oligodendroglial elements were present, (2) recurrent or progressive disease after radiation therapy, (3) measurable disease requiring a contrast-enhancing lesion with a diameter of at least 1 cm on magnetic resonance imaging (MRI) or computed tomography (CT) scan, (4) no progressive neurologic deficits or new deficits interfering with function, (5) no tumor causing midline shift or brainstem compression, (6) adequate hematologic, renal, and hepatic function, (7) World Health Organization performance status of 0 to 2, and (8) written informed consent. Patients undergoing surgery for the present recurrence were eligible provided they still had measurable disease (enhancing lesions with a diameter ≥ 1 cm) on imaging obtained within 3 days of surgery. Patients were included based on the diagnosis made by the local pathologist, with subsequent central histology review (J.M.K.). For pathology review, centers were required to submit blocks or unstained slides. Before the activation of the study, all centers required approval of their ethic committees.
The primary end point of the study was response. Secondary end points included toxicity, time to tumor progression, overall survival, and response duration. The objective response rate and its 95% confidence intervals (CI) were calculated by pooling the complete response (CR) and partial response (PR) rates. TTP and overall survival (OS) were measured from the start of chemotherapy. OS was measured until the date of death or last follow-up examination. TTP was measured until the first sign of radiologic or clinical progression (whichever came first) or last follow-up visit otherwise. OS and TTP were estimated using the Kaplan-Meier method.7
Patients were registered at the EORTC Data Center in Brussels according to the two-stage Minimax Simon Design.8 As a first step, 16 patients were entered. If fewer than three responses were observed in this group, the study would be stopped. Three responding patients in this cohort assures, with 95% power and a type I error of 10%, that a minimal response rate of 25% was reached and, in that case, 14 more patients would be registered to evaluate whether the true response rate is 50%. Because it was foreseen that pathology review would not confirm the OD in 10% of patients, in the first step, two additional patients were included, and in the second step, enrollment continued until 33 OD had been diagnosed by the review pathologist. If a total of 11 responses were obtained, the regimen would be recommended for further research in phase III studies.
Patients were treated with 200 mg/m2 of TMZ on days 1 through 5 in 28-day cycles for a maximum of 12 cycles. Dose reductions were made as previously described.5 Hematologic parameters were assessed at baseline and on days 21 and 28 of each cycle. Electrolytes, renal function, and hepatic function were assessed at baseline and on day 28 of each cycle. Response was evaluated every two cycles for the first six cycles and thereafter every three cycles. Response was evaluated preferably with MRI, but CT was allowed provided that the same imaging modality was used throughout the entire treatment. For evaluation, the image with the largest tumor area was used. Tumor size was defined as the product of the two largest perpendicular tumor diameters. CR was defined as disappearance of all contrast-enhancing tumor on two subsequent scans at least 1 month apart, with the patient being off corticosteroids and neurologically stable or improved. PR was defined as 50% or more reduction in cross-sectional contrast-enhancing tumor area on two subsequent scans at least 1 month apart, with corticosteroid use stable or decreased and the patient being neurologically stable or improved. Progressive disease was defined as 25% or more increase in cross-sectional contrast-enhancing tumor area, new tumor on CT or MRI, or neurologic deterioration and corticosteroid use stable or increased. All other situations were considered stable disease.9 The scans of all patients in which a response (CR or PR) was reported were centrally reviewed. Toxicity was assessed according to the National Cancer Institute common toxicity criteria (December 1994 version).
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RESULTS
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Thirty-nine patients were enrolled by eight institutions between December 1998 and January 2001. One patient refused treatment after entry and was subsequently lost to follow-up. This patient was not included in analyses. Patients and pretreatment characteristics are listed in Table 1 . Pathology review did not confirm the presence of an OD in three patients (pure astrocytic tumors, two patients; ependymoma, one patient). At the time of this report (June 2002), 14 patients have died and 33 have developed progressive disease (median follow-up, 20.4 months).
A total of 319 cycles of TMZ were administered (median, 10 cycles; range, 1 to 14), and 17 patients received the intended 12 cycles. Treatment was generally well tolerated. In 69% of patients, all cycles were delivered at more than 90% of the intended dose-intensity. Thirty-eight cycles were dose reduced (11% of patients); 48 cycles (15% of patients) were dose delayed. Most of the dose delays or reductions were because of hematologic toxicity. In 10 patients (13 cycles; 4%) treatment was complicated by a grade 3 or 4 hematologic toxicity (granulocytopenia, thrombocytopenia, or both). Grade 3/4 nausea and/or vomiting was observed in two patients (three cycles) and was in subsequent cycles easily managed with prophylactic antiemetics. One patient developed a grade 4 infection during a grade 4 thrombocytopenia and leukopenia after cycle 1. Although he discontinued treatment because of prolonged thrombocytopenia, he recovered without sequelae.
Twenty patients responded to TMZ (Fig 1), for a response rate of 20 (53%) of 38 patients (95% CI, 35.8% to 69.0%). In the patients with confirmed OD pathology, the response rate was 19 (54.3%) of 35 patients (95% CI, 36.7% to 71.2%; Table 2). Three patients were treated immediately after second surgery, and two of these achieved a CR to treatment. At central MRI review, all had measurable disease at immediate postoperative MRI. The median TTP was 10.4 months for all patients and 13.2 months for responding patients (CR and PR). At 6 and at 12 months, respectively, 71% and 40% of the patients were still free from progression. Median survival has not yet been reached. Fourteen of 27 patients with pure OD, three of six patients with a mixed OA, and three of five patients with other diagnoses at review or no review responded (CR or PR). All but one CR was observed in pure ODs.
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Fig 1. Complete response lasting 16 months in a 57-year-old woman treated after first surgery and radiotherapy in 1994 for a low-grade oligodendroglioma and second surgery for an anaplastic recurrence (histology: Smith D) in July 1999. At postoperative imaging, no measurable disease was present and the patient was followed; at subsequent imaging, she developed a progressive enhancing lesion. (A) November 1999, before temozolomide, and (B) after eight cycles.
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Table 2. Response to First-Line Chemotherapy With Temozolomide in Patients With Recurrent Oligodendroglial Tumors
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DISCUSSION
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This is the first study to report results of first-line chemotherapy with TMZ in recurrent OD. This study, which applied strict criteria for response, including central response review and central pathology review, showed an objective response rate of 54%. In half of the responding patients, a CR was obtained. This outcome compares favorably with the response rates to PCV of 60% to 70% and TTP in responding patients of 12 to 18 months in historical series.1,3 With a median TTP in responding patients of 13 months, the present study shows that TMZ can be considered as first-line treatment in patients with recurrent OD. For inclusion in the present study, we required the presence of an enhancing lesion, implying that even prior low-grade tumors presumably had undergone transformation into a high-grade tumor. With the increasing evidence that a specific genetic subset of OD characterized by the combined loss of 1p and 19q is sensitive to chemotherapy, the tumor grade of the tumor seems to be less relevant for the treatment outcome than the lineage of the tumor.10,11
At the time this study was designed, it was felt that for patients eligible for this study, standard treatment (PCV chemotherapy) was available. We therefore wanted to avoid the inclusion of patients with large lesions causing a mass effect or progressive neurologic deficits interfering with function. The rationale for this exclusion criterion was our fear that those patients might show a rapid clinical deterioration in case of no response, without the possibility for salvage treatment with PCV. This did not result, however, in the inclusion of small tumors only (Fig 1 ). As in previous studies on PCV chemotherapy in OD, no relationship between the size of the tumor and response was observed, and we have no indication that the outcome of the present study is biased by the inclusion of patients with more favorable tumors.3 It may still be that the generally good performance status of our patients (82% with World Health Organization performance status of 0 or 1) influenced the outcome. However, the advantage of testing a new drug in first line is obvious: it allows the determination of activity in a patient population without drug-induced resistance to chemotherapy.
As noted before, treatment with TMZ was well tolerated.5,12 The most frequent toxicity was hematologic, and only one patient had to discontinue treatment because of (reversible) thrombocytopenia. The toxicity of this oral treatment was mild, and most of the treatment cycles were administered at the intended dose-intensity. All grade 3 and 4 drug-related toxicities resolved without sequelae.
Previous studies of second-line TMZ in unselected patients with recurrent OD after prior PCV chemotherapy reported objective response rates of approximately 25%, with 11% to 27% of patients remaining free from progression at 12 months.12–14 As expected, TMZ is much more active as first-line treatment of this tumor type. The pivotal study on TMZ with recurrent anaplastic astrocytoma and mixed OA reported a response rate of 43% in 65 chemotherapy-naive patients, with a median TTP of 6.2 months.5 The present study confirms our expectation that the outcome to TMZ would be better in OD tumors as compared with anaplastic astrocytoma. Together, these data give accumulating evidence of the activity of TMZ in glial tumors and underline the need to further investigate the role of TMZ in these tumors. This should be aimed at the development of combination schedules as well as of the investigation of TMZ in more rare CNS tumors.
Recent studies have shown that, in particular, ODs with combined loss of the short arm of chromosome 1 (1p) and of the long arm of chromosome 19 (19q) are sensitive to PCV chemotherapy, with 95% to 100% of patients responding to PCV.11,15 Approximately 60% to 70% of patients with OD have this combined genetic loss. We are presently investigating whether the same relation between genotype and response to chemotherapy is present in patients treated with first-line temozolomide.
The PCV schedule was until recently considered standard treatment for patients with chemotherapy-sensitive gliomas. Despite the widespread assumption that this combination is well tolerated, many patients suffer from significant hematologic and general side effects and do not tolerate the intended number of six cycles. With the ease and tolerability of TMZ, this drug is increasingly being used as first-line chemotherapy in all glial tumors. In view of its better tolerance, even a slightly lower response rate of TMZ may still imply a more favorable treatment result for patients. We are therefore planning a phase III study comparing TMZ with the PCV regimen, with quality of life as one of the major end points.
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NOTES
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Supported in part by a grant from Schering-Plough, Kenilworth, NJ. Presented orally at the Thirty-Eighth Annual Meeting of the American Society of Clinical Oncology, Orlando, FL, May 18-21, 2002, and at the Fifth Congress of the European Association for Neuro-Oncology, Florence, Italy, September 7–10, 2002.
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REFERENCES
|
|---|
1. Cairncross G, Macdonald D, Ludwin S, et al: Chemotherapy for anaplastic oligodendroglioma. J Clin Oncol 12:2013–2021, 1994[Abstract/Free Full Text]
2. Paleologos N, Macdonald D, Vick NA, et al: Neoadjuvant procarbazine, CCNU and vincristine for anaplastic and aggressive oligodendroglioma. Neurology 53:1141–1143, 1999[Abstract/Free Full Text]
3. van den Bent MJ, Kros JM, Heimans JJ, et al: Response rate and prognostic factors of recurrent oligodendroglioma treated with PCV chemotherapy. Neurology 51:1140–1145, 1998[Abstract/Free Full Text]
4. Soffietti R, Ruda R, Bradac GB, et al: PCV chemotherapy for recurrent oligodendrogliomas and oligoastrocytomas. Neurosurgery 43:1066–1073, 1998[CrossRef][Medline]
5. Yung WKA, Prados M, Yaya-Tur R, et al: Multicenter phase II trial of temozolomide in patients with anaplastic astrocytoma or anaplastic oligoastrocytoma at first relapse. J Clin Oncol 17:2762–2771, 1999[Abstract/Free Full Text]
6. Osoba D, Brada M, Yung WKA, et al: Health realted quality of life in patients with anaplastic astrocytoma during treatment with temozolomide. Eur J Cancer 36:1788–1795, 2000[CrossRef][Medline]
7. Kaplan EL, Meier P: Nonparametric estimation from incomplete observations. J Am Stat Assoc 53:457–481, 1958[CrossRef]
8. Simon R: Optimal two-stage designs for phase II clinical trials. Control Clin Trials 10:1–10, 1989[Medline]
9. Macdonald DR, Cascino TL, Schold SC, et al: Response criteria for phase II studies of supratentorial malignant glioma. J Clin Oncol 8:1277–1280, 1990[Abstract]
10. Cairncross JG, Ueki K, Zlatescu MC, et al: Specific genetic predictors of chemotherapeutic response and survival in patients with anaplastic oligodendrogliomas. J Natl Cancer Inst 90:1473–1479, 1998[Abstract/Free Full Text]
11. van den Bent MJ, Looijenga LHJ, Langenberg K, et al: Chromosomal anomalies in oligodendroglial tumors are correlated with clinical features. Cancer 97:1276–1284, 2003[CrossRef][Medline]
12. van den Bent MJ, Keime-Guibert F, Brandes AA, et al: Temozolomide chemotherapy in recurrent oligodendroglioma. Neurology 57:340–342, 2001[Abstract/Free Full Text]
13. Constanza A, Borgogne M, Nobile M, et al: Temozolomide in recurrent oligodendroglioma: A phase II study. Neuro-Oncology 3:S66, 2001 (abstr, suppl)
14. van den Bent MJ, Chinot O, Boogerd W, et al: EORTC Brain Tumor Group study 26972: Second line chemotherapy with temozolomide in recurrent oligodendroglioma after PCV-chemotherapy—A phase II study. Ann Oncol 14:599–602, 2003[Abstract/Free Full Text]
15. Ino Y, Betensky RA, Zlatescu MC, et al: Molecular subtypes of anaplastic oligodendroglioma: Implications for patient management at diagnosis. Clin Cancer Res 7:839–845, 2001[Abstract/Free Full Text]
Submitted December 2, 2002;
accepted April 14, 2003.
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hym132v1.
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|
|
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|
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|
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|
|
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|
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|
|
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|
|
|
|
|
|
|
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|
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|
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|
|
|
|
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|
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|
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|
|
|
|
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|
|
|
|
|
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|
|
|
|
|
|
|
E. Greanya, S. Taylor, F H. BscPharm, J Barnett, and B Thiessen
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|
|
|
|
|
|
|
V. H.J.M. Triebels, M. J.B. Taphoorn, A. A. Brandes, J. Menten, M. Frenay, A. Tosoni, J. M. Kros, E. B.-t. Stege, R. H. Enting, A. Allgeier, et al.
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|
|
|
|
|
|
|
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[PDF]
|
|
|
|
|
|
|
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CpG Island Hypermethylation of the DNA Repair Enzyme Methyltransferase Predicts Response to Temozolomide in Primary Gliomas
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August 1, 2004;
10(15):
4933 - 4938.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
A. Pace, A. Vidiri, E. Galie, M. Carosi, S. Telera, A. M. Cianciulli, P. Canalini, D. Giannarelli, B. Jandolo, and C. M. Carapella
Temozolomide chemotherapy for progressive low-grade glioma: clinical benefits and radiological response
Ann. Onc.,
December 1, 2003;
14(12):
1722 - 1726.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
TOP
ABSTRACT
INTRODUCTION
