GOG0182-ICON5: 5-arm phase III randomized trial of paclitaxel (P) and carboplatin (C) vs combinations with gemcitabine (G), PEG-lipososomal doxorubicin (D), or topotecan (T) in patients (pts) with advanced-stage epithelial ovarian (EOC) or primary peritoneal (PPC) carcinoma

2006 ◽  
Vol 24 (18_suppl) ◽  
pp. 5002-5002 ◽  
Author(s):  
M. A. Bookman
Keyword(s):  
Stage Iv ◽  
Progression Free Survival ◽  
Consensus Conference ◽  
Phase Iii ◽  
Clinical Activity ◽  
Hematologic Toxicity ◽  
Type I ◽  
Standard Regimen ◽  
Initial Surgery ◽  
Event Triggered

5002 Background: P-C is a global standard for treatment of EOC and PPC (GCIG Consensus Conference 2005). Although effective, most patients recur with resistant disease. Agents were selected for new combinations based on clinical activity, interaction with cisplatin in tumor models, and feasibility. Methods: Eligible pts had appropriate initial surgery without other therapy, GOG/WHO PS 0–2, and adequate vital organ function. Pts were stratified by group, diagnosis (EOC vs PPC), stage (III vs IV), macroscopic residual tumor (yes vs no), and intent for interval cytoreduction (yes vs no). An event-triggered interim analysis (IA) of progression-free survival (PFS) was to identify arms for full accrual. The primary endpoint was overall survival (OS), determined by an event-triggered pair-wise comparison to the standard regimen (intent-to-treat), with a 90% chance of detecting a true hazard ratio (HR) of 1.33, limiting type I error to 1.25% (two-tailed) for each comparison. Sample size to be adjusted based on accrual rate and IA. Results: Accrual exceeded 1200/yr. IA for PFS (May 2004) with 1,345 events. Median PFS ranged from 15.4–17.5 m. PFS HRs ranged from 0.94–1.07 with the standard error of each log HR approximately 0.086. Extension was not recommended, and accrual closed at 4312 pts (177 ineligible). Median age 58 yrs; 13% PPC, 14% stage IV, 22% microscopic. 81% completed therapy, 4% progressed, 9% discontinued for toxicity. At least 42 deaths possibly treatment-related (<1%). Expected hematologic toxicity related to regimen intensity. Conclusions: For the regimens evaluated, there is no evidence that adding a third active cytotoxic agent prolongs PFS in EOC. Analysis of OS and impact of stratification factors are in progress. [Table: see text] [Table: see text]

Randomized Phase III Trial of Paclitaxel and Carboplatin Versus Paclitaxel and Ifosfamide in Patients With Carcinosarcoma of the Uterus or Ovary: An NRG Oncology Trial

2022 ◽  
Author(s):  
Matthew A. Powell ◽  
Virginia L. Filiaci ◽  
Martee L. Hensley ◽  
Helen Q. Huang ◽  
Kathleen N. Moore ◽  
...  
Keyword(s):  
Type I Error ◽  
Stage Iv ◽  
Progression Free Survival ◽  
Phase Iii ◽  
Hematologic Toxicity ◽  
Type I ◽  
Primary Analysis ◽  
Free Survival ◽  
Oncology Trial ◽  
Limited Precision

PURPOSE This phase III randomized trial ( NCT00954174 ) tested the null hypothesis that paclitaxel and carboplatin (PC) is inferior to paclitaxel and ifosfamide (PI) for treating uterine carcinosarcoma (UCS). PATIENTS AND METHODS Adults with chemotherapy-naïve UCS or ovarian carcinosarcoma (OCS) were randomly assigned to PC or PI with 3-week cycles for 6-10 cycles. With 264 events in patients with UCS, the power for an overall survival (OS) hybrid noninferiority design was 80% for a null hazard ratio (HR) of 1.2 against a 13% greater death rate on PI with a type I error of 5% for a one-tailed test. RESULTS The study enrolled 536 patients with UCS and 101 patients with OCS, with 449 and 90 eligible, respectively. Primary analysis was on patients with UCS, distributed as follows: 40% stage I, 6% stage II, 31% stage III, 15% stage IV, and 8% recurrent. Among eligible patients with UCS, PC was assigned to 228 and PI to 221. PC was not inferior to PI. The median OS was 37 versus 29 months (HR = 0.87; 90% CI, 0.70 to 1.075; P < .01 for noninferiority, P > .1 for superiority). The median progression-free survival was 16 versus 12 months (HR = 0.73; P = < 0.01 for noninferiority, P < .01 for superiority). Toxicities were similar, except that more patients in the PC arm had hematologic toxicity and more patients in the PI arm had confusion and genitourinary hemorrhage. Among 90 eligible patients with OCS, those in the PC arm had longer OS (30 v 25 months) and progression-free survival (15 v 10 months) than those in the PI arm, but with limited precision, these differences were not statistically significant. CONCLUSION PC was not inferior to the active regimen PI and should be standard treatment for UCS.

Phase II randomized trial of docetaxel plus cetuximab or bortezomib in patients with advanced NSCLC and performance status (PS) 2—CALGB 30402

2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 7595-7595 ◽  
Author(s):  
R. Lilenbaum ◽  
X. Wang ◽  
L. Gu ◽  
J. Kirshner ◽  
E. Vokes
Keyword(s):  
Phase Ii ◽  
Type I Error ◽  
Advanced Nsclc ◽  
Performance Status ◽  
Stage Iv ◽  
Progression Free Survival ◽  
Hematologic Toxicity ◽  
Type I ◽  
Weekly Schedule ◽  
Male Response

7595 Background: There is no standard treatment for patients (pts) with advanced NSCLC and PS 2. Docetaxel (D) is active and well tolerated on a weekly schedule. Cetuximab (C) and Bortezomib (B) are new agents with activity in NSCLC. We explored these two new combinations in PS 2 pts. Methods: In a multi-center randomized phase II trial, untreated pts with advanced NSCLC and PS 2 were randomized to D 30 mg/m2 d1,8,15 q. 28 days in combination with either C 400 mg/m2 week 1 then 250 mg/m2 weekly, or B 1.6 mg/m2 d1,8,15 q. 28 days for 4 cycles. Pts with CR/PR/SD were allowed to continue C or B until PD. The study was non-comparative and the primary endpoint was progression-free survival (PFS) rate at 6 months. The trial had a type I error of 0.0746 and power of 0.9 to differentiate a 6-mo PFS of <20% vs. >42%. Results: 64 pts were enrolled between 7/05 and 9/06. 5 were ineligible and 3 never received protocol treatment. Results are reported for 55 pts (27 D+C; 28 D+B). Most pts had stage IV adenoCa and 13% had brain metastases. Median age was 70 (range, 35–88) and 65% were male. Response: 10.5% for D+C and 13.6% for D+B. Median PFS was 3.1 mo for D+C and 1.8 mo for D+B. PFS rates at 4 mo (data not yet mature for 6-mo): 33% and 28%, respectively. Median survival: 3.8 mo for D+C and 3.3 mo for D+B. Gr 3/4 hematologic toxicity was 17% in both arms. Gr 3/4 non-heme toxicities were 44% in D+C and 36% in D+B arm. 5 pts died of treatment-related toxicities (3 D+C; 2 D+B). Conclusions: These results confirm the poor prognosis associated with a PS of 2. Based on our preliminary analysis, neither combination produced results that justify further research in this subset of patients. The treatment of PS 2 patients with advanced NSCLC remains a vexing problem and new approaches are urgently needed. No significant financial relationships to disclose.

Randomized, open-label, phase III study of pemetrexed plus carboplatin (PemC) followed by maintenance pemetrexed versus paclitaxel/carboplatin/bevacizumab (PCB) followed by maintenance bevacizumab in patients with advanced nonsquamous (NS) non-small cell lung cancer (NSCLC).

2013 ◽  
Vol 31 (18_suppl) ◽  
pp. LBA8003-LBA8003 ◽  
Author(s):  
Ralph Zinner ◽  
Helen J. Ross ◽  
Robert Weaver ◽  
Ramaswamy Govindan ◽  
Viran R. Holden ◽  
...  
Keyword(s):  
Safety Data ◽  
Stage Iv ◽  
Progression Free Survival ◽  
Drug Regimen ◽  
Primary Objective ◽  
Phase Iii ◽  
Rank Test ◽  
Type I ◽  
Open Label ◽  
Grade 3

LBA8003 Background: PemC and PCB are regimens used for first-line treatment of advanced NS-NSCLC. The primary objective was to compare progression-free survival without Grade 4 toxicity (G4PFS) between two vs three drug regimen arms. Methods: Patients ≥18 years, Stage IV NS NSCLC, AJCC (v7.0), and ECOG PS 0/1 were enrolled. Patients were randomized (1:1); received 4 cycles of induction (PemC: Pem, 500 mg/m2 and C, AUC = 6; PCB: P, 200 mg/m2, C, AUC = 6, and B, 15 mg/kg) followed by Pem (PemC Arm) or B (PCB Arm) maintenance therapy in the absence of progressive disease or discontinuation. Secondary endpoints were PFS, overall survival (OS), overall response rate (ORR), and disease control rate (DCR). The study was powered for G4PFS; assuming hazard ratio (HR) of 0.75; there was 80% power to detect superiority of PemC over PCB with a 2-sided type I error of 0.10. Efficacy data were analyzed by intent-to-treat principle using the log-rank test for time-to-event variables, and an exact test for ORR and DCR. Safety data were evaluated using CTCAE v3 for patients who received ≥1 dose of study treatment. Results: Patients were randomized to PemC (N = 182) or PCB (N = 179). Baseline factors were balanced between arms: median age 66/66 years; % female 42/42; % PS=0, 47/47; % stage IV M1a 29/30; for PemC vs PCB, median G4PFS (months) was 3.91/2.86 (HR = 0.85, 90% CI 0.7, 1.04, p = 0.176); PFS and OS had HR = 1.06 (95% CI 0.84, 1.35), p = 0.610, and HR = 1.07 (95% CI 0.83, 1.36), p = 0.616, respectively. The ORR (%) 23.6/ 27.4 and DCR (%) 59.9/57.0 were for PemC vs PCB, respectively. Significantly more drug-related grade 3/4 anemia (18.7% vs 5.4%), and thrombocytopenia (24.0% vs 9.6%) were seen on PemC; significantly more grade 3/4 neutropenia (48.8% vs 24.6%) and grade 1/2 alopecia (28.3 % vs 8.2%) were seen on PCB. Conclusions: PemC was not superior to PCB in G4PFS; no difference in PFS or OS was observed for the two- vs three-drug regimens. There were no unexpected toxicities; the toxicity profiles demonstrated distinctions by arm, and both regimens demonstrated tolerability. Clinical trial information: NCT00948675.

A multicenter phase II study of cisplatin (C), gemcitabine (G), and bevacizumab (B) as first-line chemotherapy for metastatic urothelial carcinoma (UC): Hoosier Oncology Group GU-0475

2009 ◽  
Vol 27 (15_suppl) ◽  
pp. 5018-5018
Author(s):  
N. M. Hahn ◽  
W. M. Stadler ◽  
R. T. Zon ◽  
D. M. Waterhouse ◽  
J. Picus ◽  
...  
Keyword(s):  
Performance Status ◽  
Progression Free Survival ◽  
Complete Response ◽  
Phase Iii ◽  
Clinical Activity ◽  
Hematologic Toxicity ◽  
First Line ◽  
Ecog Performance Status ◽  
Angiogenic Therapy ◽  
Grade 3

5018 Background: Despite CG therapy, most metastatic UC patients die from their disease. Novel approaches are needed. Combining anti-angiogenic therapy with chemotherapy has improved outcomes in other malignancies, offering hope for similar improvements in UC patients. Methods: Metastatic or unresectable chemonaive UC patients (pts) with an ECOG performance status of 0–1 received C 70 mg/m2 iv d1, G 1,000–1,250 mg/m2 iv d1, 8, and B 15 mg/kg iv d1 on a q21d cycle for up to 8 cycles. Gemcitabine was reduced to 1,000 mg/m2 iv d1, 8 for all subsequent pts after 7 thromboembolic events were noted in the first 17 pts. The primary endpoint was progression free survival (PFS). The trial was designed to detect a 33% improvement in PFS from 7.5 months with traditional CG therapy to 11.25 months with CGB. Results: By December 2008, 45 pts were enrolled, with 43 evaluable for toxicity, 36 for response. Demographics include: 33 (77%) male, 10 (23%) female; median age 66 (Range: 41 - 78); 26 (60%) and 17 (40%) ECOG 0/1; 19 (44%) and 24 (56%) lymph node only / visceral metastases. PFS will be evaluated in May 2009 when all pts will have more than 6 month follow-up data. 14 (33%) and 6 (14%) pts experienced grade 3 or 4 hematologic toxicity (4 pts - thrombocytopenia, 2 pts - neutropenic fever). Grade 3 or 4 nonhematologic toxicity was observed in 24 (56%) and 9 (21%) pts (DVT/PE - 9 pts, CNS hemorrhage/proteinuria/hypertension - 1 pt each) Best RECIST response was: complete response 6 pts (17%, 95% CI 6–33%), partial response 18 pts (50%, 95% CI 33–67%); with overall response rate of 67% (95% CI 51–82%). Stable disease lasting at least 12 weeks was observed in 10 pts (28%, 95% CI 14–45%) and progressive disease in 2 pts (5%, 95% CI 1–19%). Conclusions: CGB demonstrates significant clinical activity in the first-line treatment of metastatic UC patients at the expense of considerable toxicity. The durability of disease control will be determined by assessment of PFS. A phase III trial to further define the toxicity risk vs. clinical benefit of bevacizumab addition to platinum-based doublets is planned in this population. [Table: see text]

A randomized, multicenter, phase II trial of gemcitabine (G), cisplatin (C) +/- veliparib (V) in patients with pancreas adenocarcinoma (PDAC) and a known germline (g)BRCA/ PALB2 mutation.

2020 ◽  
Vol 38 (4_suppl) ◽  
pp. 639-639 ◽  
Author(s):  
Eileen Mary O'Reilly ◽  
Jonathan W. Lee ◽  
Mark Zalupski ◽  
Marinela Capanu ◽  
Jennifer Park ◽  
...  
Keyword(s):  
Phase Ii ◽  
Phase Ii Trial ◽  
Stage Iv ◽  
Progression Free Survival ◽  
Stage Iii ◽  
Rank Test ◽  
Hematologic Toxicity ◽  
Type I ◽  
Exact Test ◽  
Entire Cohort

639 Background: gBRCA 1,2 mutations occur in 5-8% PDAC. Platinum and poly-ADP ribose polymerase inhibitors (PARPi) effective in BRCA-mut cancers. Phase I GC + V high RR 78%; combination may delay resistance in PDAC (O’Reilly, Cancer, 2018). Herein, we evaluate GC +/- V in a multi-national, randomized phase II trial. Methods: Eligibility: Untreated germline (g)BRCA, PALB2 mut PDAC; measurable stage III/IV; ECOG 0-1. Randomized 1:1 Arm A or B. Treatment: Arm A: G 600 mg/m2 IV, C 25 mg/m2 IV, d3 and 10, V 80 mg PO BID day 1-12, all q 3 weeks or Arm B: GC only. Primary endpoint: RECIST 1.1 response rate (RR). Simon 2-stage per arm: null hypothesis 10% vs promising 28%; type I, II error 10%. Secondary endpoints: progression-free survival (PFS), OS (m), disease control rate (CR+PR+SD), safety and correlative analyses. PFS, OS compared between arms using log-rank test and RR, DCR using Fisher’s exact test between arms. Results: N = 52 enrolled 01/14- 11/18. N = 2 withdrew Arm B. N = 50 for ITT. Male = 22 (44%), Female = 28. Median age = 64 years (range 37-82). BRCA1 N = 12, BRCA2 N = 35, PALB2 N = 3. Stage III N = 8; Stage IV N = 42. Hematologic Toxicity: Arm A vs Arm B: Gd 3-4 neutropenia 13 (48%) vs 7 (30%); Gd 3-4 platelets 15 (55%) vs 2 (9%); Gd 3-4 anemia 14 (52%) vs 8 (35%). Non-hematologic toxicity similar Arm A vs B. Exploratory analyses (combined Arms): Med OS if > 4 m platinum → PARPi: 23 m (95%CI 6.5- 53.9). Med OS by BRCA: BRCA1: 14 m (8.1- 18.5); BRCA2: 20.2 m (12.3- 24.4). Med OS by ECOG: ECOG 0: 23 m (13.8- 24.5); ECOG 1: 14.3 (8.1 vs 16.4). Two-year OS rate for entire cohort: 30.6% and 3-year OS: 17.8%. Conclusions: GC +/- V very active in gBRCA/PALB2 mut PDAC with high RR, PFS, OS with both A, B significantly exceeding threshold RR. Improved DCR arm A vs B, but with greater heme toxicity A vs B. Study confirms GC as reference treatment in gBRCA/PALB2 with durable survival in subset. Funding: National Cancer Institute, CTEP, Lustgarten Foundation, AbbVie. Clinical trial information: NCT01585805 . [Table: see text]

scholarly journals Bevacizumab for Newly Diagnosed Ovarian Cancers: Best Candidates Among High-Risk Disease Patients (ICON-7)

2020 ◽  
Vol 4 (3) ◽  
Author(s):  
Olivier Colomban ◽  
Michel Tod ◽  
Julien Peron ◽  
Timothy J Perren ◽  
Alexandra Leary ◽  
...  
Keyword(s):  
High Risk ◽  
Elimination Rate ◽  
Stage Iv ◽  
Progression Free Survival ◽  
Phase Iii ◽  
Stage Iii ◽  
Absolute Difference ◽  
Ca 125 ◽  
Ovarian Cancers ◽  
High Risk Disease

Abstract Bevacizumab is approved as a maintenance treatment in first-line setting in advanced-stage III-IV ovarian cancers, because GOG-0218 and ICON-7 phase III trials demonstrated progression-free survival benefits. However, only the subgroup of patients with high-risk diseases (stage IV, and incompletely resected stage III) derived an overall survival (OS) gain in the ICON-7 trial (4.8 months). The modeled CA-125 elimination rate constant K (KELIM) parameter, based on the longitudinal CA-125 kinetics during the first 100 days of chemotherapy, is a potential indicator of the tumor primary chemo-sensitivity. In the ICON-7 trial dataset, the OS of patients within the low- and high-risk disease groups was assessed according to treatment arms and KELIM. Among the patients with high-risk diseases, those with favorable standardized KELIM of at least 1.0 (n = 214, 46.7%) had no survival benefit from bevacizumab, whereas those with unfavorable KELIM less than 1.0 (n = 244, 53.2%) derived the highest OS benefit (absolute difference = 9.1 months, 2-sided log-rank P = .10; Cox hazard ratio = 0.78, 95% confidence interval = 0.58 to 1.04, 2-sided P = .09).

Combination Chemoimmunotherapy with Pentostatin, Cyclophosphamide and Rituximab Shows Significant Clinical Activity with Low Accompanying Toxicity in Previously Untreated B-Chronic Lymphocytic Leukemia.

Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 35-35
Author(s):  
Neil Kay ◽  
Susan Geyer ◽  
Timothy Call ◽  
Tait Shanafelt ◽  
Clive Zent ◽  
...  
Keyword(s):  
Flow Cytometry ◽  
High Risk ◽  
Chronic Lymphocytic Leukemia ◽  
Residual Disease ◽  
Progression Free Survival ◽  
Lymphocytic Leukemia ◽  
Clinical Activity ◽  
Hematologic Toxicity ◽  
Free Survival ◽  
Significant Clinical Activity

Abstract BACKGROUND: B-Chronic Lymphocytic Leukemia (CLL) is still uncurable but very powerful new tools are available with the use of chemoimmunotherapy (CIT). Purine nucleoside-based regimens that incorporate rituximab have generated very high levels of overall responses (OR) with significant percentage of those complete responses (CR) in previously untreated CLL. Here we report and update our experience with a phase 2 pentostatin-based CIT regimen for previously untreated CLL as conducted at 2 medical centers. We also studied the association of outcome based on risk stratification parameters and achievement of minimal residual disease. METHODS: Building on prior work of pentostatin in CLL by us (Kay ASH, 2004) and others, we initiated a trial of combined pentostatin (P)(2 mg/m2), cyclophosphamide (C)(600 mg/m2) and rituximab (R)(375 mg/m2) for symptomatic, previously untreated patients (n=65). This PCR regimen is given on a 21-day, 6-cycle schedule. However, the initial cycle of treatment uses thrice weekly rituximab as described by us earlier. In brief, this was rituximab at 100 mg/m2 on day 1, 375 mg/m2 on days 3 and 5 of the first week only. Prophylactic Sulfamethoxazole/Trimethoprim and Acyclovir were given to all patients for 1 year starting on the first cycle of therapy with PCR. All patients were risk stratified using CD38, ZAP-70, immunoglobulin heavy chain variable region gene (IgVH) and FISH panel assessments at entry. RESULTS: These patients were characterized as mostly in high-risk categories. Of 64 evaluable patients, 34 (53%) were high Rai risk (stage 3–4), 71% were non mutated for the IgVH gene, 34% were CD38+ and 34% were ZAP-70+. Thirty patients (52%) had one FISH anomaly, and 21 (36%) had complex FISH defects. Thirty-eight patients (58%) had grade 3+ hematologic toxicity but minimal transfusion needs, and no major infections. NCI Working Group Criteria Responses occurred in 58 (91%) with 26 (41%) complete responses (CR), 14 (22%) nodular partial responses (nodular PR), and 18 (28%) partial responses (PR) patients. Outcome for all 64 patients demonstrates a median progression-free survival of 32.6 months. Importantly, no high risk factor (i.e., age, FISH, IgVH status, CD38+, ZAP-70+) except for del (17p) defect (n=3) precluded attaining a CR or NPR. In contrast, we found this regimen was equally effective in young vs. elderly (>70 yrs) patients and in del(11)(q22.3) vs. other favorable prognostic FISH factors. Examination of outcome among CR and nodular PR patients for PFS by flow cytometry status (negative vs. positive, i.e., ≤ 1 % CD5+/CD19+ vs. ≥ 1 % CD5+/CD19+) demonstrated improvement in progression free survival for patients who attained flow cytometry negativity (p = 0.009). Conclusion: This novel regimen of pentostatin, cyclophosphamide and rituximab for previously untreated CLL demonstrated significant clinical activity despite poor risk-based prognoses with minimal toxicity in terms of bone marrow suppression and/or infections. The additional feature of this approach is the ability to have durable responses for all age groups and even CLL patients with a del(11)(q22.3).

Efficacy Of Bendamustine and Rituximab In Patients With Relapsed/Refractory Chronic Lymphocytic Leukemia

Blood ◽  
2013 ◽  
Vol 122 (21) ◽  
pp. 5312-5312
Author(s):  
Elena Kataeva ◽  
Anatoly Golenkov ◽  
Elena Triphonova ◽  
Galina Dudina ◽  
Tatyana Mitina ◽  
...  
Keyword(s):  
Conflicts Of Interest ◽  
Haematological Toxicity ◽  
Stage Iv ◽  
Previous Treatment ◽  
Progression Free Survival ◽  
Peripheral Blood Lymphocytes ◽  
Lymphocytic Leukemia ◽  
Hematologic Toxicity ◽  
Prior Therapy ◽  
Intravenous Infusions

Abstract The objective of the study was to assess the efficacy and safety of the Bendamustine (B) and Rituximab (R) combination therapy in pre-treated patients with relapsed/refractory chronic lymphocytic leukaemia (CLL). Patients and Methods 13 patients with CLL were examined, out of which 9 were men and 4 women. The average age of the enrolled patients was 62 years (52-77). 5 CLL patients had RAI stage II, 1-III and 7 patients had stage IV. FISH test detected del (17p) in 4 patients (30.8%), del (11q) in 3 patients (13.1%) the immunophenotype test of peripheral blood lymphocytes identified 5 patients (38.5%) with CD38+positive (cut off over 20%). The patients received prior therapy with COP, CHOP, RFC, FC, RCHOP, FluCam, Alemtuzumab and R courses. The treatment lasted for 23.7 months (12-36). 10.4 (7-20) treatment courses were made on average. Median of Chemotherapy lines in each patient was 4 (2-5). All the patients were resistant to the previous treatment and relapsed. The patients received R through intravenous infusions at a dose of 500 mg/m2 on day 1 of the therapy course and B through intravenous infusions at a dose of 100 mg/m2 on days 2 and 3 of the therapy course, and the course was repeated every 28 days. 4.6 (3-9) therapy courses were administered. Results All the patients (100%) responded to the administered therapy by achieving partial remission. Progression-free survival within 6 months is 67%. Median of the examination was 12.3 months (4-33) and 9 patients (69%) are alive. 3 patients (21%) had hematologic toxicity of levels 3 and 4. At the same time 2 patients (14%) had neutropenia, and 1 patient (7%) had thrombocytopenia respectively. 3 patients (23%) had non-haematological toxicity of level III in the form of infections (pneumonia) and 3 patients (27%) had gastroenterological toxicity. Conclusion thus, the BR combination has a high anticancer activity in heavily pre-treated patients with relapsed/refractory CLL. It should be noted that the examined patients had pejorative prognostic characters such as del (17p) and del 11(q), and high CD 38+ expression (82.4%). At the same time the toxicity profile was low. Good anticancer effect and moderate toxicity indicate strict selectivity of the BR program. Disclosures: No relevant conflicts of interest to declare.

UW-01: A randomized comparison of three doses of weekly docetaxel as 1st-line chemotherapy in stage IV breast cancer

2006 ◽  
Vol 24 (18_suppl) ◽  
pp. 10522-10522
Author(s):  
J. R. Gralow ◽  
D. Chielens ◽  
G. Schuster ◽  
B. Storer ◽  
M. J. McCleod ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Stage Iv ◽  
Phase Iii ◽  
Study Endpoint ◽  
Primary Study ◽  
Hematologic Toxicity ◽  
Stage Iv Breast Cancer ◽  
Study Results ◽  
Significant Difference ◽  
Grade 3

10522 Background: Docetaxel (DOC) is an active agent in the treatment of breast cancer. The optimal dose and dosing interval for DOC, with respect to balancing efficacy and toxicity, has yet to be determined. In this multi-center, randomized phase III trial, we attempted to compare 3 doses of single-agent weekly DOC. Methods: Patients with documented evaluable or measurable stage IV breast cancer and no prior metastatic chemotherapy were eligible. Prior adjuvant chemotherapy was permitted if ≥ 6 months had elapsed. Adjuvant exposure to DOC was allowed if ≥ 1 year prior. All patients received intravenous weekly DOC, 3 out of 4 weeks. Patients on Arm A received doses of 25 mg/m2, Arm B received 30 mg/m2, and Arm C received 35 mg/m2. The primary study outcome was time to progression (TTP). Secondary endpoints included toxicity, response rate (RR), and overall survival (OS). Targeted accrual was 600 patients. Results: The study was stopped early for feasibility reasons (poor accrual) after a total of 108 patients were enrolled at 49 U.S. sites. The median patient age was 63 years. Grade 3, 4 non-hematologic toxicity was 22%, 22%, and 23% in Arms A, B and C respectively. Nail toxicity of any grade occurred in 2 patients in Arm A, 6 patients in Arm B, and 7 patients (2 of which were grade 3) in Arm C. TTP for Arm A was 19 weeks (95% confidence intervals [CI] 10–23), 28 weeks for Arm B (95% CI 15–38), and 24 weeks for Arm C (95% CI 12–37). There was a marginally significant difference in TTP between arms A and C (HR = 1.7, 95% CI = 1.0–2.8, p = 0.05), but not between arms B and C (HR = 1.0, 95% CI 0.6–1.7, p = 0.94). RR was 26%, 27%, and 31% in Arms A, B and C, respectively. Median survival was 77 weeks for Arm A (95% CI 53–115), and 96 weeks for arm B (95% CI 53-undetermined); it has not yet been reached for Arm C. Discussion: The interpretation of study results is limited due to early stopping and resultant loss of statistical power. For the primary study endpoint, TTP, the lowest (25 mg/m2) dose may be less than optimal, but there was no observed difference between the intermediate (30 mg/m2) and highest doses (35 mg/m2) of weekly DOC. Grade 3, 4 non-hematologic toxicities were similar between the 3 arms. [Table: see text]

A randomized phase II trial of concurrent temozolomide (TMZ) and radiotherapy (RT) followed by dose dense compared to metronomic TMZ and maintenance cis-retinoic acid for patients with newly diagnosed glioblastoma multiforme (GBM)

2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 2031-2031 ◽  
Author(s):  
J. Sul ◽  
K. S. Panageas ◽  
A. B. Lassman ◽  
A. Hormigo ◽  
C. Nolan ◽  
...  
Keyword(s):  
Retinoic Acid ◽  
Dna Methyltransferase ◽  
Progression Free Survival ◽  
Phase Iii ◽  
Hematologic Toxicity ◽  
Newly Diagnosed ◽  
Methylguanine Dna Methyltransferase ◽  
Angiogenic Therapy ◽  
Progression Of Disease ◽  
Dose Dense

2031 Background: Metronomic and dose dense scheduling are alternatives to conventional TMZ regimens to overcome drug resistance in part by depleting O-6 methylguanine-DNA methyltransferase (MGMT). Furthermore, metronomic TMZ may inhibit endothelial recovery and act as an anti-angiogenic therapy; dose dense TMZ increases the intensity of drug delivery. Objective: To determine the overall (OS) and progression free survival (PFS) of patients with newly diagnosed GBM treated with concurrent TMZ and RT followed by dose dense or metronomic TMZ and maintenance cis-retinoic acid. Methods: Patients with newly diagnosed, histologically confirmed GBM underwent standard RT with TMZ. Upon completion of this treatment, patients were randomized to receive dose-dense TMZ (150mg/m2, days 1–7 and 15–21 of a 28 day cycle) or metronomic TMZ (50mg/m2 daily in 28 day cycles), for 6 cycles. Maintenance cis-retinoic acid was prescribed following the 6 cycles of adjuvant TMZ. OS and PFS were calculated from date of diagnosis. Prospective correlative tissue analysis of MGMT status is planned. A Simon minimax 2-stage design was used for each cohort. If either group has 70% survival probability at 1 year, further evaluation in a phase III trial will be recommended. Results: 51 patients were randomized: 24 to metronomic, and 27 to dose dense. Median age is 57, and median KPS 90. 26 patients have progression of disease (POD), with a median follow up of 5 months. Grade 3/4 hematologic toxicity occurred in 7 patients (14%), 3 in the metronomic and 4 in the dose dense arm. Conclusions: Our patient population is comparable to that of other upfront GBM treatment trials. Metronomic and dose dense TMZ appear to be well tolerated with equivalent toxicities. Early analysis suggests that patients on the dose dense regimen may have better PFS than those on the metronomic arm. [Table: see text] No significant financial relationships to disclose.

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