Phase III Study Comparing Three Cycles of Infusional Carmustine and Cisplatin Followed by Radiation Therapy With Radiation Therapy and Concurrent Carmustine in Patients With Newly Diagnosed Supratentorial Glioblastoma Multiforme: Eastern Cooperative Oncology Group Trial 2394

2003 ◽  
Vol 21 (8) ◽  
pp. 1485-1491 ◽  
Author(s):  
Stuart A. Grossman ◽  
Anne O’Neill ◽  
Margaret Grunnet ◽  
Minesh Mehta ◽  
James L. Pearlman ◽  
...  
Keyword(s):  
Radiation Therapy ◽  
Glioblastoma Multiforme ◽  
Median Survival ◽  
Performance Status ◽  
Eastern Cooperative Oncology Group ◽  
Phase Iii ◽  
Rank Test ◽  
Newly Diagnosed ◽  
Oncology Group ◽  
Ambulatory Treatment

Purpose: This phase III Eastern Cooperative Oncology Group-Southwest Oncology Group intergroup study was conducted to determine whether three 72-hour infusions of carmustine (BiCNU) and cisplatin administered monthly before external-beam radiotherapy would improve the survival of patients with newly diagnosed glioblastoma multiforme. The control arm consisted of radiation with standard adjuvant BiCNU. Patients and Methods: A total of 223 patients were accrued from 1996 to 1999. Of these, 219 patients were eligible; 109 were randomly assigned to the experimental arm, and 110 were randomly assigned to the control arm. Randomization was stratified by age, performance status, and extent of resection. Results: The median age of the patients was 55 years; 55% were male, 93% were white, 26% had a biopsy only, and 84% were ambulatory. Treatment arms were well balanced with respect to baseline characteristics. Median follow-up time of the 15 patients still alive at the time of analysis was 3.3 years (range, 2 to 5 years). Median survival times for the standard and experimental arms were 11.2 and 11.0 months (P = .33, two-sided log-rank test), and survival at 1 year was 45% versus 44%, respectively. Fifty-six percent of patients received all three cycles of BiCNU/cisplatin, 12% received two cycles, and 31% received only one cycle. Toxicity was primarily hematologic and was more common in the experimental arm (P < .01). Conclusion: This study demonstrates that 72-hour infusions of BiCNU and cisplatin followed by radiation do not improve median survival, survival at 1 year, or time to progression. Furthermore, this treatment requires more time in the hospital and is associated with more serious toxicities than standard therapy.

scholarly journals Phase III Randomized, Placebo-Controlled Trial of Docetaxel With or Without Gefitinib in Recurrent or Metastatic Head and Neck Cancer: An Eastern Cooperative Oncology Group Trial

2013 ◽  
Vol 31 (11) ◽  
pp. 1405-1414 ◽  
Author(s):  
Athanassios Argiris ◽  
Musie Ghebremichael ◽  
Jill Gilbert ◽  
Ju-Whei Lee ◽  
Kamakshi Sachidanandam ◽  
...  
Keyword(s):  
Head And Neck ◽  
Disease Progression ◽  
Kinase Inhibitor ◽  
Performance Status ◽  
Single Agent ◽  
Eastern Cooperative Oncology Group ◽  
Phase Iii ◽  
Oncology Group ◽  
Ecog Performance Status ◽  
Grade 3

Purpose We hypothesized that the addition of gefitinib, an epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor, to docetaxel would enhance therapeutic efficacy in squamous cell carcinoma of the head and neck (SCCHN). Patients and Methods Patients with recurrent or metastatic SCCHN with Eastern Cooperative Oncology Group (ECOG) performance status of 2, or patients with ECOG performance status of 0 to 2 but were previously treated with chemotherapy, were randomly assigned to receive weekly docetaxel plus either placebo (arm A) or gefitinib 250 mg/d, orally (arm B) until disease progression. At the time of progression, patients in the placebo arm could receive single-agent gefitinib. EGFR, c-MET, and KRAS mutations and polymorphisms in drug metabolizing enzymes and transporters were evaluated by pyrosequencing. Results Two hundred seventy patients were enrolled before the study was closed early at interim analysis (arm A, n = 136; arm B, n = 134). Median overall survival was 6.0 months in arm A versus 7.3 months in arm B (hazard ratio, 0.93; 95% CI, 0.72 to 1.21; P = .60). An unplanned subset analysis showed that gefitinib improved survival in patients younger than 65 years (median 7.6 v 5.2 months; P = .04). Also, there was a trend for improved survival in patients with c-MET wild-type (5.7 v 3.6 months; P = .09) regardless of treatment. Grade 3/4 toxicities were comparable between the two arms except that grade 3/4 diarrhea was more common with docetaxel/gefitinib. Of 18 eligible patients who received gefitinib after disease progression in arm A, one patient had a partial response. Conclusion The addition of gefitinib to docetaxel was well tolerated but did not improve outcomes in poor prognosis but otherwise unselected patients with SCCHN.

MGMT methylation in newly-diagnosed glioblastoma multiforme (GBM): From the S0001 phase III study of radiation therapy (RT) and O6-benzylguanine, (O6BG) plus BCNU versus RT and BCNU alone for newly diagnosed GBM

2006 ◽  
Vol 24 (18_suppl) ◽  
pp. 1512-1512 ◽  
Author(s):  
D. T. Blumenthal ◽  
M. Wade ◽  
C. J. Rankin ◽  
F. Fitzpatrick ◽  
K. Stelzer ◽  
...  
Keyword(s):  
Glioblastoma Multiforme ◽  
Median Survival ◽  
Promoter Methylation ◽  
Promoter Region ◽  
Alkylating Agents ◽  
Methylation Status ◽  
Phase Iii ◽  
Newly Diagnosed ◽  
Tissue Samples ◽  
Mgmt Promoter

1512 Background: Glioblastoma multiforme (GBM) is a high grade primary brain neoplasm associated with a median survival of less than a year. Historically, one-third of patients seem to benefit from treatment with alkylating chemotherapy. This minority may correspond to a population with decreased levels of active O6-methylguanine- methyltransferase enzyme (MGMT). MGMT repairs tumor DNA damaged by chemotherapy, allowing continued replication after exposure to treatment. Patients with low tumor MGMT activity may be more likely to respond to alkylating treatment. Hypermethylation of the MGMT promoter region leads to decreased transcription of the enzyme and is associated with improved outcome in GBM patients treated with radiation and alkylating chemotherapy. Methods: We studied a patient cohort with newly diagnosed GBM registered on Southwest Oncology Group protocol S0001, a phase III randomized, two arm clinical trial investigating an inhibitor of MGMT (O6-benzylguanine, O6BG). Both groups received standard radiation and BCNU (carmustine). The experimental group additionally received O6BG. We determined polymerase chain reaction (PCR) methylation status of the promoter region of MGMT in 88 patients with adequate tissue samples. In 41 cases, we were able to obtain successful PCR results. Results: 28 of 41 samples (68%) were found to be unmethylated and 13 of 41 (32%, 95% c. i. 18% to 50%) were methylated. Patients with methylated MGMT had a median survival of 12.6 months (95% c.i. of 7.8–15.8 months). Patients with unmethylated MGMT had a median survival of 10.6 months (95% c.i. of 8.7–12.0 months). Median progression-free survivals were 4.5 and 3.1 months respectively, for the methylated and unmethylated groups. Conclusions: This result is consistent with prior studies which showed that approximately two-thirds of patients express MGMT, and accordingly, are resistant to alkylating agents. The subgroup of patients without promoter methylation may be more likely to benefit from treatment with O6BG. Analysis of MGMT promoter methylation status per study treatment group, and correlation with median survival and progression-free survival will be presented. No significant financial relationships to disclose.

Topotecan Is an Active Agent in the First-Line Treatment of Metastatic or Recurrent Endometrial Carcinoma: Eastern Cooperative Oncology Group Study E3E93

2003 ◽  
Vol 21 (11) ◽  
pp. 2110-2114 ◽  
Author(s):  
Scott Wadler ◽  
Donna E. Levy ◽  
Sarah T. Lincoln ◽  
Gamini S. Soori ◽  
Julian C. Schink ◽  
...  
Keyword(s):  
Radiation Therapy ◽  
Endometrial Carcinoma ◽  
Topoisomerase I ◽  
Performance Status ◽  
Eastern Cooperative Oncology Group ◽  
Active Agent ◽  
Clinical Activity ◽  
Oncology Group ◽  
Ecog Performance Status ◽  
Prophylactic Use

Purpose: To determine the clinical activity and the toxicity profile of the topoisomerase-I inhibitor, topotecan, in women with recurrent or advanced endometrial carcinoma.Patients and Methods: A prospective, phase II clinical trial was initiated by the Eastern Cooperative Oncology Group (ECOG). Patients had histologically confirmed advanced or recurrent endometrial carcinoma, measurable disease, no prior cytotoxic therapy, an ECOG performance status of 0 to 2, and evidence of disease progression while on progestins or after radiation therapy. Topotecan was administered at 1.5 mg/m2(or 1.2 mg/m2for patients with prior pelvic radiation) intravenously daily for 5 days every 3 weeks.Results: A total of 44 patients were enrolled; 42 were eligible. The study was suspended because of unexpected toxicities, primarily sepsis and bleeding. After toxicity review, the study was reopened using lower doses of topotecan (1.0 mg/m2or 0.8 mg/m2for patients with prior radiation therapy). In addition, prophylactic use of growth factors was allowed after the first cycle, and patients with performance status of 2 were excluded. The major toxicities were hematologic and gastrointestinal. Among the 40 assessable patients, there were three (7.5%) complete responders and five partial responders (12.5%), for an overall response rate of 20%. The median duration of response was 8.0 months and of overall survival was 6.5 months.Conclusion: Topotecan is an active agent for the treatment of advanced endometrial carcinoma. At the doses and schedules initially used, toxicities were unacceptable; however, at the modified doses, toxicities were acceptable and clinical activity was preserved.

Abbreviated Course of Radiation Therapy in Older Patients With Glioblastoma Multiforme: A Prospective Randomized Clinical Trial

2004 ◽  
Vol 22 (9) ◽  
pp. 1583-1588 ◽  
Author(s):  
W. Roa ◽  
P.M.A. Brasher ◽  
G. Bauman ◽  
M. Anthes ◽  
E. Bruera ◽  
...  
Keyword(s):  
Overall Survival ◽  
Radiation Therapy ◽  
Glioblastoma Multiforme ◽  
Older Patients ◽  
Treatment Time ◽  
Karnofsky Performance Status ◽  
Performance Status ◽  
Wilcoxon Test ◽  
Rank Test ◽  
Survival Times

Purpose To prospectively compare standard radiation therapy (RT) with an abbreviated course of RT in older patients with glioblastoma multiforme (GBM). Patients and Methods One hundred patients with GBM, age 60 years or older, were randomly assigned after surgery to receive either standard RT (60 Gy in 30 fractions over 6 weeks) or a shorter course of RT (40 Gy in 15 fractions over 3 weeks). The primary end point was overall survival. The secondary end points were proportionate survival at 6 months, health-related quality of life (HRQoL), and corticosteroid requirement. HRQoL was assessed using the Karnofsky performance status (KPS) and Functional Assessment of Cancer Therapy-Brain (FACT-Br). Results All patients had died at the time of analysis. Overall survival times measured from randomization were similar at 5.1 months for standard RT versus 5.6 months for the shorter course (log-rank test, P = .57). The survival probabilities at 6 months were also similar at 44.7% for standard RT versus 41.7% for the shorter course (lower-bound 95% CI, −13.7). KPS scores varied markedly but were not significantly different between the two groups (Wilcoxon test, P = .63). Low completion rates of the FACT-Br (45%) precluded meaningful comparisons between the two groups. Of patients completing RT as planned, 49% of patients (standard RT) versus 23% required an increase in posttreatment corticosteroid dosage (χ2 test, P = .02). Conclusion There is no difference in survival between patients receiving standard RT or short-course RT. In view of the similar KPS scores, decreased increment in corticosteroid requirement, and reduced treatment time, the abbreviated course of RT seems to be a reasonable treatment option for older patients with GBM.

GliaSite Brachytherapy for Treatment of Recurrent Malignant Gliomas:A Retrospective Multi-institutional Analysis

Neurosurgery ◽  
2006 ◽  
Vol 58 (4) ◽  
pp. 701-709 ◽  
Author(s):  
Arash J. Gabayan ◽  
Sylvan B. Green ◽  
Abhay Sanan ◽  
Joseph Jenrette ◽  
Christopher Schultz ◽  
...  
Keyword(s):  
Radiation Therapy ◽  
Glioblastoma Multiforme ◽  
Median Survival ◽  
Karnofsky Performance Status ◽  
External Beam Radiotherapy ◽  
Performance Status ◽  
Malignant Gliomas ◽  
Balloon Catheter ◽  
Median Dose ◽  
Karnofsky Performance Status Score

Abstract OBJECTIVE: To review the cumulative experience of 10 institutions in treating recurrent malignant gliomas with the brachytherapy device, GliaSite Radiation Therapy System. METHODS: The patient population consisted of 95 patients with recurrent grade 3 or 4 gliomas, a median age of 51 years, and a median Karnofsky performance status score of 80. All patients had previously undergone resection and had received external beam radiotherapy as part of their initial treatment. After recurrence, each patient underwent maximal surgical debulking of their recurrent lesion and placement of an expandable balloon catheter (GliaSite) in the tumor cavity. The balloon was afterloaded with liquid 125I (Iotrex) to deliver a median dose of 60 Gy to an average depth of 1 cm with a median dose rate of 52.3 Gy/hr. Patients were carefully followed with serial magnetic resonance imaging and monthly examinations for tumor progression, side effects, and survival. RESULTS: The median survival for all patients, measured from date of GliaSite placement, was 36.3 weeks with an estimated 1 year survival of 31.1%. The median survival was 35.9 weeks for patients with an initial diagnosis of glioblastoma multiforme and 43.6 weeks for those with non- glioblastoma multiforme malignant gliomas. Analysis of the influence of various individual prognostic factors on patient survival demonstrated that only Karnofsky performance status significantly predicted for improved survival. There were three cases of pathologically documented radiation necrosis. CONCLUSION: Reirradiation of malignant gliomas with the GliaSite Radiation Therapy System after reresection seems to provide a modest survival benefit above what would be expected from surgery alone. This report not only confirms the initial results of the feasibility study but provides evidence that similar outcomes can be obtained outside of a clinical trial.

Topotecan Versus Observation After Cisplatin Plus Etoposide in Extensive-Stage Small-Cell Lung Cancer: E7593—A Phase III Trial of the Eastern Cooperative Oncology Group

2001 ◽  
Vol 19 (8) ◽  
pp. 2114-2122 ◽  
Author(s):  
Joan H. Schiller ◽  
Sudeshna Adak ◽  
David Cella ◽  
Russell F. DeVore ◽  
David H. Johnson
Keyword(s):  
Quality Of Life ◽  
Performance Status ◽  
Eastern Cooperative Oncology Group ◽  
Small Cell ◽  
Phase Iii ◽  
Oncology Group ◽  
Small Cell Lung ◽  
Phase Iii Trial ◽  
Extensive Stage

PURPOSE: To determine the efficacy of topotecan in combination with standard chemotherapy in previously untreated patients with extensive-stage small-cell lung cancer (SCLC), the Eastern Cooperative Oncology Group (ECOG) conducted a phase III trial. PATIENTS AND METHODS: Eligible patients had measurable or assessable disease and an ECOG performance status of 0 to 2; stable brain metastases were allowed. All patients received four cycles of cisplatin and etoposide every 3 weeks (step 1; PE). Patients with stable or responding disease were then randomized to observation or four cycles of topotecan (1.5 mg/m2/d for 5 days, every 3 weeks; step 2). A total of 402 eligible patients were registered to step 1, and 223 eligible patients were registered to step 2 (observation, n = 111; topotecan, n = 112). RESULTS: Complete and partial response rates to induction PE were 3% and 32%, respectively. A 7% response rate was observed with topotecan (complete response, 2%; partial response, 5%). The median survival time for all 402 eligible patients was 9.6 months. Progression-free survival (PFS) from date of randomization on step 2 was significantly better with topotecan compared with observation (3.6 months v 2.3 months; P < .001). However, overall survival from date of randomization on step 2 was not significantly different between the observation and topotecan arms (8.9 months v 9.3 months; P = .43). Grade 4 neutropenia and thrombocytopenia occurred in 50% and 3%, respectively, of PE patients in step 1 and 60% and 13% of topotecan patients in step 2. Grade 4/5 infection was observed in 4.6% of PE patients and 1.8% of topotecan patients. Grade 3/4 anemia developed in 22% of patients who received topotecan. No difference in quality of life between topotecan and observation was observed at any assessment time or for any of the subscale scores. CONCLUSION: Four cycles of PE induction therapy followed by four cycles of topotecan improved PFS but failed to improve overall survival or quality of life in extensive-stage SCLC. Four cycles of standard PE remains an appropriate first-line treatment for extensive-stage SCLC patients with good performance status.

Phase III Study of the Eastern Cooperative Oncology Group (ECOG 2597): Induction Chemotherapy Followed by Either Standard Thoracic Radiotherapy or Hyperfractionated Accelerated Radiotherapy for Patients With Unresectable Stage IIIA and B Non–Small-Cell Lung Cancer

2005 ◽  
Vol 23 (16) ◽  
pp. 3760-3767 ◽  
Author(s):  
Chandra P. Belani ◽  
Wei Wang ◽  
David H. Johnson ◽  
Henry Wagner ◽  
Joan Schiller ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Radiation Therapy ◽  
Small Cell Lung Cancer ◽  
Induction Chemotherapy ◽  
Median Survival ◽  
Eastern Cooperative Oncology Group ◽  
Small Cell ◽  
Oncology Group ◽  
Small Cell Lung ◽  
Stage Iiia

Purpose To compare once-daily radiation therapy (qdRT) with hyperfractionated accelerated radiation therapy (HART) after two cycles of induction chemotherapy. Patients and Methods Eligible patients were treatment naive, and had stage IIIA and B unresectable non-small-cell lung cancer, Eastern Cooperative Oncology Group performance status 0/1, and normal organ function. Induction chemotherapy consisted of two cycles of carboplatin area under time-concentration curve 6 mg/mL · min plus paclitaxel 225 mg/m2 on day 1. RT consisted of arm 1 (qdRT), 64 Gy (2 Gy/d), versus arm 2 (HART), 57.6 Gy (1.5 Gy tid for 2.5 weeks). A total of 388 patients were needed to detect a 50% increase in median survival from 14 months of qdRT to 21 months of HART; accrual was not achieved and the study closed prematurely. Results Of 141 patients enrolled, 83% were randomly assigned after chemotherapy to qdRT (n = 59) or HART (n = 60). Median survival was 20.3 and 14.9 months for HART and qdRT, respectively (P = .28). Overall response was 25% and 22% for HART and qdRT, respectively (P = .69). Two- and 3-year survival was 44% and 34% for HART, and 24% and 14% for qdRT, respectively. Grade ≥ 3 toxicities included esophagitis in 14 v nine patients, and pneumonitis in 0 v 6 patients for HART and qdRT, respectively. Any subsequent trials of the HART regimen must address the issues that led to early closure, including slow accrual, logistics of HART, mucosal toxicity, and the fact that concurrent chemoradiotherapy now seems more effective than sequential treatment. Conclusion After two cycles of induction chemotherapy with carboplatin-paclitaxel, HART is feasible with an acceptable toxicity profile. Although statistical significance was not achieved and the study closed early, there was a positive statistical trend suggesting a survival advantage with the HART regimen.

Phase III Trial of Carmustine and Cisplatin Compared With Carmustine Alone and Standard Radiation Therapy or Accelerated Radiation Therapy in Patients With Glioblastoma Multiforme: North Central Cancer Treatment Group 93-72-52 and Southwest Oncology Group 9503 Trials

2006 ◽  
Vol 24 (24) ◽  
pp. 3871-3879 ◽  
Author(s):  
Jan C. Buckner ◽  
Karla V. Ballman ◽  
John C. Michalak ◽  
Gary V. Burton ◽  
Terrence L. Cascino ◽  
...  
Keyword(s):  
Radiation Therapy ◽  
Glioblastoma Multiforme ◽  
Median Survival ◽  
Survival Rates ◽  
Sensory Neuropathy ◽  
Phase Iii ◽  
Survival Times ◽  
North Central ◽  
Newly Diagnosed Glioblastoma ◽  
Improvement In Survival

Purpose In patients with newly diagnosed glioblastoma multiforme, to determine whether cisplatin plus carmustine (BCNU) administered before and concurrently with radiation therapy (RT) improves survival compared with BCNU and RT and whether survival using accelerated RT (ART) is equivalent to survival using standard RT (SRT). Patients and Methods After surgery, patients were stratified by age, performance score, extent of surgical resection, and histology (glioblastoma v gliosarcoma) and then randomly assigned to arm A (BCNU plus SRT), arm B (BCNU plus ART), arm C (cisplatin plus BCNU plus SRT), or arm D (cisplatin plus BCNU plus ART). Results Four hundred fifty-one patients were randomly assigned, and 401 were eligible. Frequent toxicities included myelosuppression, vomiting, sensory neuropathy, and ototoxicity and were worse with cisplatin. There was no difference in toxicity between SRT and ART. Median survival times and 2-year survival rates for patients who received BCNU plus RT (arms A and B) compared with cisplatin, BCNU, and RT (arms C and D) were 10.1 v 11.5 months, respectively, and 11.5% v 13.7%, respectively (P = .19). Median survival times and 2-year survival rates for patients who received SRT (arms A and C) compared with ART (arms B and D) were 11.2 v 10.5 months, respectively, and 13.8% v 11.4%, respectively (P = .33). Conclusion Cisplatin administered concurrently with BCNU and RT resulted in more toxicity but provided no significant improvement in survival. SRT and ART produced similar toxicity and survival.

scholarly journals Real-world validity of randomized controlled phase III trials in newly diagnosed glioblastoma: to whom do the results of the trials apply?

2021 ◽  
Vol 3 (1) ◽  
Author(s):  
Erlend Skaga ◽  
Marthe Andrea Skretteberg ◽  
Tom Børge Johannesen ◽  
Petter Brandal ◽  
Einar O Vik-Mo ◽  
...  
Keyword(s):  
Clinical Trials ◽  
Real World ◽  
Performance Status ◽  
Geographical Area ◽  
Eastern Cooperative Oncology Group ◽  
University Hospital ◽  
Phase Iii ◽  
Newly Diagnosed ◽  
Eligibility Criteria ◽  
Phase Iii Trials

Abstract Background The survival rates in population-based series of glioblastoma (GBM) differ substantially from those reported in clinical trials. This discrepancy may be attributed to that patients recruited to trials tend to be younger with better performance status. However, the proportion and characteristics of the patients in a population considered either eligible or ineligible for trials is unknown. The generalizability of trial results is therefore also uncertain. Methods Using the Cancer Registry of Norway and the Brain Tumor Database at Oslo University Hospital, we tracked all patients within a well-defined geographical area with newly diagnosed GBM during the years 2012–2017. Based on data from these registries and the medical records, the patients were evaluated for trial eligibility according to criteria employed in recent phase III trials for GBM. Results We identified 512 patients. The median survival was 11.7 months. When we selected a potential trial population at the start of concurrent chemoradiotherapy (radiotherapy [RT]/ temozolomide [TMZ]) by the parameters age (18–70 y), passed surgery for a supratentorial GBM, Eastern Cooperative Oncology Group (ECOG) ≤2, normal hematologic, hepatic and renal function, and lack of severe comorbidity, 57% of the patients were excluded. Further filtering the patients who progressed during RT/TMZ and never completed RT/TMZ resulted in exclusion of 59% and 63% of the patients, respectively. The survival of patients potentially eligible for trials was significantly higher than of the patients not fulfilling trial eligibility criteria (P &lt; .0001). Conclusions Patients considered eligible for phase III clinical trials represent a highly selected minority of patients in a real-world GBM population.

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