Biweekly oxaliplatin plus capecitabine (OXXEL) versus oxaliplatin plus folinic acid-modulated 5-fluorouracil i.v. bolus (OXAFAFU) in metastatic colorectal carcinoma (MCC): Safety interim analysis of a Southern Italy Cooperative Oncology Group (SICOG) phase III trial

2006 ◽  
Vol 24 (18_suppl) ◽  
pp. 3590-3590 ◽  
Author(s):  
C. Sandomenico ◽  
G. Filippelli ◽  
B. Massidda ◽  
A. Farris ◽  
D. Natale ◽  
...  
Keyword(s):  
Folinic Acid ◽  
Interim Analysis ◽  
Median Number ◽  
Phase Iii ◽  
Hematologic Toxicity ◽  
Who Grade ◽  
Hand Foot Syndrome ◽  
Present Trial ◽  
Metastatic Sites ◽  
Oxxel Regimen

3590 Background: We have previously reported that OXAFAFU regimen significantly prolonged the overall survival of MCC patients (pts) in comparison with IRIFAFU regimen (Comella, Ann Oncol 2005). Moreover, the OXXEL regimen showed promising activity in phase II study (Comella, Cancer Chemother Pharmacol 2005). Comparison of these two regimens in terms of safety and activity is the aim of the present trial. Methods: Pts with MCC were randomly treated with: oxaliplatin 85 mg/m2 iv on day (D) 1, levo-folinic acid 250 mg/m2 plus 5-fluorouracil 850 mg/m2 bolus iv on D 2 (OXAFAFU); or oxaliplatin 100 mg/m2 iv on D 1, Xeloda 1,000 mg/m2 twice daily po from D 1 (evening) to D 11 (morning). Treatment was delivered every 2 weeks up to progression, or for a maximum of 12 cycles. Results: From May 2004 to December 2005, 191 eligible pts were recruited (OXAFAFU, 96 pts; OXXEL, 95 pts). Characteristics of pts were well balanced in OXAFAFU vs OXXEL arm: primary colon, 74% vs 72%; PS 0/1–2, 57/43% vs 65/35%; previous adjuvant CT, 24% vs 20%; liver metastases, 80% vs 83%; ≥ 2 metastatic sites, 54% vs 49%. At this interim analysis, with a median number of 8 (range, 1–12) cycles delivered in both arms, 143 pts (OXAFAFU, 73; OXXEL, 70) were assessed for safety. In OXAFAFU vs OXXEL arm, occurrence of WHO grade ≥ 3 toxicity was: neutropenia, 29% vs 3%; anemia, 2% vs 7%; thrombocytopenia 3% vs 7%; diarrhea, 4% vs 13%; vomiting, 4% vs 3%; hand-foot syndrome, 1% vs 7%. Conclusions: At this interim analysis, the OXXEL regimen appeared to produce significantly less neutropenia than the OXAFAFU regimen, at a price of an acceptable non-hematologic toxicity. Accrual will continue up to reaching the final sample size of 300 pts. No significant financial relationships to disclose.

Tolerability and Efficacy of Bortezomib Added to CVP-R for Previously Untreated Advanced Stage Follicular Lymphoma: Interim Analysis of a Phase II Study by the NCIC Clinical Trials Group.

Blood ◽  
2008 ◽  
Vol 112 (11) ◽  
pp. 1576-1576 ◽  
Author(s):  
Laurie H Sehn ◽  
David A Macdonald ◽  
Sheldon H. Rubin ◽  
Morel Rubinger ◽  
Kevin R Imrie ◽  
...  
Keyword(s):  
Follicular Lymphoma ◽  
Phase Ii ◽  
Interim Analysis ◽  
Standard Dose ◽  
Single Agent ◽  
Acceptable Level ◽  
Phase Iii ◽  
Hematologic Toxicity ◽  
Open Label ◽  
Grade 3

Abstract Background: Despite recent improvements in therapy, follicular lymphoma (FL) remains incurable with standard treatment, warranting investigation of new approaches. Bortezomib, the first-in-class proteasome inhibitor has demonstrated promising efficacy as a single agent in heavily pretreated patients (pts) with FL. This is the first study to evaluate the safety and efficacy of the addition of bortezomib to cyclophosphamide, vincristine, prednisone and rituximab (CVP-R). Methods: This is a phase II multi-center open-label trial adding bortezomib (1.3 mg/m2 day 1&8) to standard dose C(750 mg/m2) V(1.4 mg/m2, capped at 2 mg) P(40 mg/m2 × 5) –R(375 mg/m2) for up to 8 cycles in pts with newly diagnosed stage III/IV FL requiring therapy. Planned accrual is 90 patients. A two-stage design was employed with a planned interim analysis of the first 28 patients to ensure an acceptable level of neurotoxicity (defined as less than 5/28 patients with grade 3/4 neurotoxicity after the first 4 cycles) and meaningful response rate (more than 12/28 patients with a complete response following 8 cycles), prior to enrolling remaining patients. Results: Median age of the first 28 patients was 55 years (range, 30–73). Fifty percent were male and 79% had stage IV disease. FLIPI score at study entry: low 14%, intermediate 43%, high 43%. Overall, the combination of bortezomib and CVP-R was extremely well tolerated. To date, no pts have developed grade 4 neurotoxicity and only 1/28 (4%) has developed grade 3 neurotoxicity within the first 4 cycles (neuropathic pain which resolved without need for treatment modification). The incidence of grade 1 and 2 neurotoxicity was 54% and 25% respectively. Only 3 pts discontinued therapy prematurely (2 pt refusal, 1 progressive disease). Ninety-four percent of planned bortezomib treatments in the first four cycles and 93% of vincristine doses were administered without dose reduction. Hematologic toxicity was mild, with no pts experiencing grade 3/4 anemia or thrombocytopenia. Only 2 episodes of febrile neutropenia occurred and no grade 3/4 infections were noted. Although it is too early to report on efficacy in this ongoing trial, response objectives for stage I have been met, and enrollment to stage 2 is underway. Conclusions: The addition of bortezomib to standard dose CVP-R is very well tolerated, with an acceptable level of neurotoxicity, without compromising the delivery of bortezomib or vincristine. This ongoing study will provide toxicity and efficacy data to facilitate the development of a planned phase III trial.

Phase II dose escalation study of sorafenib in patients with metastatic renal cell carcinoma (mRCC) who have had prior treatment with VEGFR-TKI antiangiogenic treatment

2009 ◽  
Vol 27 (15_suppl) ◽  
pp. e16027-e16027
Author(s):  
A. P. Mancuso ◽  
E. Donato De Paola ◽  
A. Catalano ◽  
F. Calabrò ◽  
C. Messina ◽  
...  
Keyword(s):  
Standard Dose ◽  
Progression Free Survival ◽  
Median Number ◽  
Dose Escalation Study ◽  
Multikinase Inhibitor ◽  
Prior Therapy ◽  
Hand Foot Syndrome ◽  
Tki Treatment ◽  
Number Of Cycles ◽  
Metastatic Sites

e16027 Background: Sorafenib is an orally active multikinase inhibitor (Raf kinase, VEGFR 1, 2, 3 and PDGFR inhibitor) for the treatment of advanced RCC. The purpose of this study was to assess the efficacy and toxicity of Sorafenib in mRCC patients (pts) previously treated with an anti-angiogenic VEGFR-TKI using escalating dose levels. Methods: Pts with mRCC, PS 0–2 and adequate organ function were eligible. Pts received Sorafenib 400 mg/BID/continuously in 4-wk cycles. Pts with no progressive disease (evaluated at 12 weeks) continued to receive Sorafenib at the standard dose, while progressive pts received an increasing dose (600 mg BID) with early disease restaging after 4 weeks. Pts who progressed at 600 mg BID were taken off study. Efficacy was assessed by RECIST criteria. Results: 18 pts were entered; baseline characteristics: PS 0–1: 94%; median age 62 years (41–82); nephrectomy: 100%; surgery for metastatic disease: 28%, clear-cell 78%, papillary-cell 16%, sarcomatoid 6%.≥ 2 metastatic sites: 84%. 10 pts were refractory to cytokine treatment and all progressed or experienced unacceptable toxicity after anti-angiogenic VEGFR-TKI treatment, Sunitinib (13 pts) or Pazopanib (5 pts). Median number of cycles was 7.5 (1–16). Overall, 72% of pts had disease control without significant correlations between response to prior therapy and hypertension. 14 pts had progression free survival (PFS) of 4.3 months (mos). 4 pts are still in treatment with a median PFS > 8 mos. Of 6 pts in which the dose was escalated, 3 benefitted with a PFS of > 3 mos. The most common toxicity (NCIC 3.0, all pts) was grade (g) ≥ 1 diarrhea in 10 pts, g2–3 hand-foot syndrome in 7 pts and g-3 mucositis in 1 pt. Other hematological and non-hematological toxicities were g1 with a frequency < 15%. Conclusions: Sorafenib at doses of 400–600 mg/BID/continuosly results in acceptable and well tolerated salvage treatment after VEGFR-TKI failure. In progressive patients, treatment with a higher dose could be a valid option. Final and mature data will be presented in combination with translational research evaluating biological characteristics on tissue and blood. No significant financial relationships to disclose.

Randomized Phase III Study of Capecitabine Plus Oxaliplatin Compared With Fluorouracil/Folinic Acid Plus Oxaliplatin As First-Line Therapy for Metastatic Colorectal Cancer

2008 ◽  
Vol 26 (12) ◽  
pp. 2006-2012 ◽  
Author(s):  
Jim Cassidy ◽  
Stephen Clarke ◽  
Eduardo Díaz-Rubio ◽  
Werner Scheithauer ◽  
Arie Figer ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Metastatic Colorectal Cancer ◽  
Folinic Acid ◽  
Progression Free Survival ◽  
Phase Iii ◽  
First Line ◽  
First Line Therapy ◽  
Line Therapy ◽  
Hand Foot Syndrome ◽  
Grade 3

PurposeTo evaluate whether capecitabine plus oxaliplatin (XELOX) is noninferior to fluorouracil. folinic acid, and oxaliplatin (FOLFOX-4) as first-line therapy in metastatic colorectal cancer (MCRC).Patients and MethodsThe initial design of this trial was a randomized, two-arm, noninferiority, phase III comparison of XELOX versus FOLFOX-4. After patient accrual had begun, the trial design was amended in 2003 after bevacizumab phase III data became available. The resulting 2 × 2 factorial design randomly assigned patients to XELOX versus FOLFOX-4, and then to also receive either bevacizumab or placebo. We report here the results of the analysis of the XELOX versus FOLFOX-4 arms. The analysis of bevacizumab versus placebo with oxaliplatin-based chemotherapy is reported separately. The prespecified primary end point for the noninferiority analysis was progression-free survival.ResultsThe intent-to-treat population comprised 634 patients from the original two-arm portion of the study, plus an additional 1,400 patients after the start of the amended 2 × 2 design, for a total of 2,034 patients. The median PFS was 8.0 months in the pooled XELOX-containing arms versus 8.5 months in the FOLFOX-4–containing arms (hazard ratio [HR], 1.04; 97.5% CI, 0.93 to 1.16). The median overall survival was 19.8 months with XELOX versus 19.6 months with FOLFOX-4 (HR, 0.99; 97.5% CI, 0.88 to 1.12). FOLFOX-4 was associated with more grade 3/4 neutropenia/granulocytopenia and febrile neutropenia than XELOX, and XELOX with more grade 3 diarrhea and grade 3 hand-foot syndrome than FOLFOX-4.ConclusionXELOX is noninferior to FOLFOX-4 as a first-line treatment for MCRC, and may be considered as a routine treatment option for appropriate patients.

Phase III study of gemcitabine plus vinorelbine (VG) versus vinorelbine (V) in patients (pts) with metastatic breast cancer (MBC) previously treated with anthracyclines (A) and taxanes (T). Final results of GEICAM 2000–04 study

2006 ◽  
Vol 24 (18_suppl) ◽  
pp. 575-575
Author(s):  
M. Muñoz ◽  
M. Martín ◽  
A. Ruiz ◽  
A. Balil ◽  
J. García-Mata ◽  
...  
Keyword(s):  
Objective Response ◽  
Metastatic Breast ◽  
Progression Free Survival ◽  
Median Number ◽  
Primary Objective ◽  
Phase Iii ◽  
Hematological Toxicity ◽  
Hematologic Toxicity ◽  
Previously Treated ◽  
Visceral Disease

575 Background: VG has shown to be efficacious and safe in MBC in pts previously treated with AT. This study compared treatment (TT) V with the combination of VG. Primary objective was progression free survival (PFS). Methods: pts previously treated with AT, aged ≥18, ECOG ≤ 2, were randomized to V: 30 mg/m2 day (d) 1, d8, or VG 30/1200 mg/m2 d1, d8, both every 21 days until disease progression. Stratification criteria were previous lines of TT for MBC (0 vs.1 vs.2) and visceral disease (yes vs. no). 126 pts per arm were needed to demonstrate a prolongation in PFS of 2 months (m) (from 3 to 5; HR = 1.67; α and β errors 0.05 and 10). Results: 252 pts (127 V and 125 VG) were recruited between 2001 and 2005. Arms were well balanced: median age was 57 years; median number of metastatic sites 2; visceral disease was present in 75% of pts; 17%, 53% and 29% of pts received study TT as first, second and third line respectively. Median number of cycles were 4 (1–21) in V and 6 (1–26) in VG. Median PFS was 6.3 m (95% CI, 5.3–7.3) for VG and 4.1 m (95% CI, 3.3–4.9) for V (p=0.0011). Objective response rate was 37% (CI 95% 29–46) for VG and 25% (CI 95%: 17–33) for V (p= 0.035). CTC grade 3–4 hematologic toxicity was significantly higher with VG vs. V (65% vs. 43% neutropenia, 33% vs. 17% leucopenia, and 11% vs. 2% thrombocytopenia); febrile neutropenia was present in 10.5% of pts on VG and 6% of pts in V (p=ns). Non-hematological toxicity was low and manageable in both arms. Conclusions: VG demonstrated significant efficacy advantages over V in pts with MBC previously treated with AT, with manageable toxicity. This favorable risk-benefit profile supports the use of this combination in this patient population. [Table: see text]

XELOX regimen in elderly patients with metastatic colorectal cancer (MCRC), a FNCLCC French Collaborative Group GERICO 02 phase II study

2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 19513-19513 ◽  
Author(s):  
F. Viret ◽  
R. Bugat ◽  
M. Ducreux ◽  
F. Cvitkovic ◽  
E. Carola ◽  
...  
Keyword(s):  
Elderly Patients ◽  
The Elderly ◽  
Median Number ◽  
Collaborative Group ◽  
Paired Data ◽  
Efficacy Analysis ◽  
Significant Toxicity ◽  
Hand Foot Syndrome ◽  
Metastatic Sites ◽  
The Impact

19513 Background: Xelox regimen is an active combination in 1st line MCRC. In elderly patients, independence measured by the 6-items Activity of Daily Living Katz scale (ADL) determines whether an elderly can eventually live alone. We wanted to evaluate, the impact of Xelox regimen on independence of elderly patients measured by ADL after 3 and 6 cycles (CY), the response rate and safety profile. Methods: Elderly patients above 70 with histological proven MCRC were treated with an adapted XELOX regimen capecitabine (CPT) 750 mg/m2 orally bid d1–14 + oxaliplatin (OXP) 90 mg/m2 iv d1,q3w). After 3 CY with no significant toxicity, OXP and CPT were increased to 120 mg/m2 iv d1 and 1,000 mg/m2 bid d1–14 respectively. Results: 60 patients were enrolled at 6 centers over 36 months, of the 53 analyzed to date: M/F, 30/23, median age 78 years, Karnofsky index 80, 88.68% patients had comorbidity. Metastatic sites were liver (70.59%), lung (43.14%) and bone (9.8%). 39 % of patients (20) stopped treatment prematurely: progressive disease (6), toxicity (11), patients wish (3). Median ADL baseline was high (5.5; 1.5–6). Primary endpoint was achieved: after 3 CY 32/35 (91%) had no ADL decrease (median 6; 3.5–6) and unilateral Wilcoxon tested on paired data showed ADL improvement (p=0.0001). After 6 CY, 96% of patients had no ADL decrease. Median number of CY administered was 6 (1–6) with 88.24% of patients received ≥ 3 cycles. The dose of chemotherapy OXP and/or CPT was increased in 31.6 % of the elderly patients. Efficacy analysis: 1 patient achieved CR, 19 PR, 11 SD, 11 PD, 9 NE. Toxicity was moderated: diarrhea (g3/4: 13%), neurotoxicity (g1/2: 67%, g3/4: 2%), hand-foot syndrome (g1/2:19%, g3/4: 0%) and haematological (g3/4: 12%). Conclusions: This study shows that Xelox regimen does not impair independence measured by ADL in MCRC elderly patients. It is also a safe, well tolerated (in 1st line treatment) and active regimen in this population of patients. [Table: see text]

Interim safety analysis of a compassionate-use program (CUP) and early-access program (EAP) providing cabazitaxel (Cbz) plus prednisone (P) to patients (pts) with metastatic castration-resistant prostate cancer (mCRPC) previously treated with docetaxel.

2013 ◽  
Vol 31 (15_suppl) ◽  
pp. 5055-5055 ◽  
Author(s):  
Zafar I. Malik ◽  
Giuseppe Di Lorenzo ◽  
Mert Basaran ◽  
Alexandros Ardavanis ◽  
Phillip Parente ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Performance Status ◽  
Safety Data ◽  
Real Life ◽  
Dose Intensity ◽  
Median Number ◽  
Phase Iii ◽  
Castration Resistant Prostate Cancer ◽  
Ecog Performance Status ◽  
Metastatic Sites

5055 Background: Cbz + P provides a significant survival benefit vs mitoxantrone + P in pts with mCRPC (Phase III TROPIC study [NCT00417079]; hazard ratio 0.70; p < 0.0001). These findings supported the initiation of ongoing Sanofi-funded CUP and EAP (NCT01254279) to provide access to Cbz prior to commercialization and to collect real-life safety data. Methods: Expected enrollment is ~1600 pts with mCRPC from 250 centers worldwide. Pts receive Cbz (25 mg/m2 Q3W) + P (10 mg oral QD) until progressive disease (PD), death, unacceptable toxicity, physician/pt decision or Cbz commercial availability. Pts are followed until 30 days after last dose. Granulocyte colony-stimulating factor (G-CSF) use is recommended as per ASCO guidance. Results: Interim baseline and safety data from the first 1301 pts treated in 37 countries are now available. Mean age was 68 yrs (22% were ≥ 75 yrs). All pts had an ECOG performance status ≤ 2. Median time from initial prostate cancer diagnosis was 57.6 months and 60% of pts had ≥ 2 metastatic sites; the most common were bone (91%) and lymph nodes (regional 30%, distant 27%). In total, 17% had PD whilst on docetaxel. The median number of Cbz cycles was 6 (range 1–22); median relative dose intensity was 99%. Overall, 837 pts (64%) received G-CSF (n = 123 curative [C], n = 765 prophylactic [P] and n = 99 [C + P]). Of 1142 pts (88%) who discontinued Cbz + P, the most common reasons were PD (44%), adverse event (AE; 27%), physician decision (13%) and commercial availability of Cbz (7%). Grade 3–4 AEs possibly related to Cbz + P occurred in 43% of pts; the most frequent were clinical neutropenia (18%), febrile neutropenia (FN; 7%) and diarrhea (4%). Of 80 pts (6%) with AEs leading to death, the AE was related to Cbz + P in 39 pts (3%). Conclusions: These results provide valuable data on Cbz + P treatment in routine clinical practice, confirming the safety results of clinical trials and showing that treatment with Cbz + P is associated with a manageable safety profile. The incidence of FN seems slightly lower than in TROPIC, owing to more frequent use of G-CSF prophylaxis in the CUP and EAP. Clinical trial information: NCT01254279.

Design and first interim analysis of a randomized phase III trial comparing imatinib versus imatinib (IM) based combination therapies in newly diagnosed chronic myelogenous leukemia patients in chronic phase

2006 ◽  
Vol 24 (18_suppl) ◽  
pp. 6589-6589
Author(s):  
F. Maloisel ◽  
V. Dubruille ◽  
B. Varet ◽  
M. Escoffre-Barbe ◽  
P. Berthaud ◽  
...  
Keyword(s):  
Interim Analysis ◽  
Response Rates ◽  
Myelogenous Leukemia ◽  
Phase Iii ◽  
Hematological Toxicity ◽  
Hematologic Toxicity ◽  
Molecular Response ◽  
Molecular Remission ◽  
Grade 3 ◽  
600Mg Daily

6589 Background: Despite impressive results achieved with IM 400 mg/day alone, only a minority of pts reached a complete molecular remission at 12-month. Higher dose of IM or its combination with other therapies might improve molecular remission. Design of the trial: the 3 experimental arms are IM 400mg daily in combination with Peg-IFN-α2a (Peg-IFNα2a, 90 μg weekly) or with Ara-C (20 mg/m2/day, days 15–28 of 28-day cycles) or IM 600mg daily. The reference arm is IM 400mg daily. All pts (over 18 years of age with Bcr-Abl positive CML) receive IM 400 mg/day as monotherapy days 1–14 and then start the assigned regimen for at least 12 months. The endpoints are overall survival (primary), rate and duration of hematologic, cytogenetic and molecular responses and tolerability. An interim analysis of the first 636 pts at 1 year from randomization will allow evaluation of molecular response rates, one of the experimental arm being selected for further comparison with IM 400. An experimental arm would be selected if it increased the 4 log reduction response rate at 12-month by at least 20 percentage points, (15% to 35%), with an acceptable tolerability. Results: This evaluation is based on a cohort of 370 pts with a median time of observation of 16 months, recruited between 9/2003 and 9/2005. [median age 53 yrs (18–81); Sokal distribution: 38% of pts low, 38% intermediate, and 24% high]. At 1 month 80% of pts achieved complete hematologic response. At 12 months, 138 pts (72%) achieved a major cytogenetic response, being complete in 120 pts (63%). Grade 3/4 hematologic toxicity occurred in 8% of IM400 pts, 9% of IM600 pts, 41% of IM+IFN pts and 33% of IM+Ara-c pts respectively. Dose of Peg IFN was reduced in 16% of pts, 45 μg per week being well tolerated. Grade 3/4 non hematological toxicity occurred in 11% of IM400 pts, 16% of IM600 pts, 10% of IM+IFN pts (maily skin rash) and 11% of IM+Ara-c pts. Discontinuation of experimental treatment occurred in 17% of IM600 pts, 36% of IM+IFN pts and 16% of IM+Ara-c pts. Conclusion: This first analysis confirmed both feasibility of IM combinations and high response rates. However a substantial hematological toxicity requires a careful assessment of pts. [Table: see text]

Adjuvant chemotherapy (CT) with doxorubicin and ifosfamide in resected soft tissue sarcoma (STS): Interim analysis of a randomised phase III trial

2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 10008-10008 ◽  
Author(s):  
P. J. Woll ◽  
M. van Glabbeke ◽  
P. Hohenberger ◽  
A. Le Cesne ◽  
A. Gronchi ◽  
...  
Keyword(s):  
Interim Analysis ◽  
Meta Analysis ◽  
Performance Status ◽  
Randomised Trial ◽  
Patient Characteristics ◽  
Phase Iii ◽  
Hematologic Toxicity ◽  
Disease Site ◽  
Detailed Assessment ◽  
The Impact

10008 Background: The impact of adjuvant CT on survival for resected STS remains uncertain. In a 1997 meta-analysis, doxorubicin-based CT significantly improved local and overall relapse free survival (RFS), but not overall survival. Many of the CT regimens used would now be considered suboptimal. We therefore undertook a multicentre randomised trial of intensive CT in patients with excised high grade STS. Methods: Patients with macroscopically resected, Trojani grade II-III STS at any site, no metastases, performance status (PS) <2 and age = 70 were eligible within 4 weeks of surgery. Patients were randomised to observation or CT with 5 cycles of doxorubicin 75 mg/m2, ifosfamide 5 g/m2q 21 days and lenograstim. Patients in both arms received radiotherapy (RT) if the resection was marginal or the tumor recurrent. Stratifications were for institution, disease site, tumor size, planned RT and isolated limb perfusion therapy. Results: Between 1995 and 2003, 351 patients were recruited. 9.5% were ineligible and 4.8% did not receive the allocated treatment. Patient characteristics were evenly distributed between the two arms: 47% > 50 years; 54% male; 33% PS 1. The commonest pathological subtypes were leiomyo- 15%, lipo- 13%, MFH 11%, synovial sarcoma 11%. 60% were grade III. 66% were extremity tumors. Of 175 patients allocated CT, 163 started and 127 completed 5 cycles. 38% had dose reductions or delays, mostly for hematologic toxicity or infection. 88% of patients received RT. An interim analysis for futility has been performed, because survival in the observation arm was better than expected: estimated 5-yr RFS was 52% in both arms and OS 69% (observation arm) and 64% (CT arm). The hypotheses that adjuvant CT improves RFS and OS (with hazard ratios = 0.621) can both be rejected. Conclusions: This is the largest study of adjuvant CT with ifosfamide and doxorubicin ever undertaken in STS. It fails to show a survival advantage for adjuvant CT. Improved survival over previous studies might be due to better surgery and increased use of adjuvant RT. Further analysis of this study will allow more detailed assessment of the role of adjuvant CT in resected STS and will contribute to an updated meta-analysis. [Table: see text]

scholarly journals Phase III Study of Enzastaurin Compared With Lomustine in the Treatment of Recurrent Intracranial Glioblastoma

2010 ◽  
Vol 28 (7) ◽  
pp. 1168-1174 ◽  
Author(s):  
Wolfgang Wick ◽  
Vinay K. Puduvalli ◽  
Marc C. Chamberlain ◽  
Martin J. van den Bent ◽  
Antoine F. Carpentier ◽  
...  
Keyword(s):  
Statistical Significance ◽  
Objective Response ◽  
Progression Free Survival ◽  
Well Being ◽  
Recurrent Glioblastoma ◽  
Phase Iii ◽  
Hematologic Toxicity ◽  
Open Label ◽  
Serious Adverse Events ◽  
Who Grade

PurposeThis phase III open-label study compared the efficacy and safety of enzastaurin versus lomustine in patients with recurrent glioblastoma (WHO grade 4).Patients and MethodsPatients were randomly assigned 2:1 to receive 6-week cycles of enzastaurin 500 mg/d (1,125-mg loading dose, day 1) or lomustine (100 to 130 mg/m2, day 1). Assuming a 45% improvement in progression-free survival (PFS), 397 patients were required to provide 80% power to achieve statistical significance at a one-sided level of .025.ResultsEnrollment was terminated at 266 patients (enzastaurin, n = 174; lomustine, n = 92) after a planned interim analysis for futility. Patient characteristics were balanced between arms. Median PFS (1.5 v 1.6 months; hazard ratio [HR] = 1.28; 95% CI, 0.97 to 1.70), overall survival (6.6 v 7.1 months; HR = 1.20; 95% CI, 0.88 to 1.65), and 6-month PFS rate (P = .13) did not differ significantly between enzastaurin and lomustine, respectively. Stable disease occurred in 38.5% and 35.9% of patients and objective response occurred in 2.9% and 4.3% of patients, respectively. Time to deterioration of physical and functional well-being and symptoms did not differ between arms (HR = 1.12; P = .54). Four patients discontinued enzastaurin because of drug-related serious adverse events (AEs). Eleven patients treated with enzastaurin died on study (four because of AEs; one was drug-related). All four deaths that occurred in patients receiving lomustine were disease-related. Grade 3 to 4 hematologic toxicities were significantly higher with lomustine (46 events) than with enzastaurin (one event; P ≤ .001).ConclusionEnzastaurin was well tolerated and had a better hematologic toxicity profile but did not have superior efficacy compared with lomustine in patients with recurrent glioblastoma.

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