Randomized, phase III study of carboplatin plus paclitaxel for 8 cycles (CP8) versus carboplatin x 8 cycles plus paclitaxel x 4 cycles (C8P4) in advanced ovarian, fallopian, or primary peritoneal carcinoma.

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. 5033-5033
Author(s):  
Aristotelis Bamias ◽  
Eleni Timotheadou ◽  
Gerasimos Aravantinos ◽  
Dimitrios G. Pectasides ◽  
Christos A. Papadimitriou ◽  
...  
Keyword(s):  
Residual Disease ◽  
Randomized Study ◽  
Tumor Grade ◽  
Phase Iii ◽  
Lower Grade ◽  
Phase Iii Study ◽  
Grade 3 ◽  
Number Of Cycles ◽  
Ecog Ps ◽  
Line Chemotherapy

5033 Background: The combination of carboplatin/paclitaxel represents the standard 1st-line chemotherapy in advanced OC, FC, and PPC. The optimal duration of paclitaxel treatment has not been defined, while its use is associated with cumulative neurotoxicity in about 50% of patients, which becomes long-term in 15-20% of cases. We, therefore, designed a randomized study to investigate the effect of administering 4 instead of 8 cycles of paclitaxel in the combination carboplatin/paclitaxel on efficacy and tolerability of this treatment. Methods: Patients with FIGO stages IIC-IV OC, FC, PPC were included. Carboplatin AUC 6 and paclitaxel at 175 mg/m2 were used. Both agents were administered for 8 cycles in the CP8 arm, while paclitaxel was administered only for 4 cycles in the C8P4. The study was powered to detect a ± 15% difference in survival rate to a baseline rate of 50 % at the 3-year time point. Results: 389 pts were randomized (2/2004-1/2008) and 380 were eligible for analysis (CP8: 192, C8P4:188). The distribution (CP8 vs C8P4) of baseline characteristics were: stage III: 78% vs. 76%; IV: 12% vs. 15%, residual disease 0 cm: 25% vs. 22%, ECOG PS 0: 68% vs. 64%, serous carcinomas: 79% vs. 68%, tumor grade III: 56% vs. 63%. During a median follow up of 72.3 months 231 patients (111 [58%] in CP8 arm and 120 [64%] in the C8P4 arm) have died. Median PFS was significantly shorter in the C8P4 arm (21.41 vs. 16.46 months, HR [95% CI]: 1.36 [1.07-1.71], Wald’s p=0.011), while OS was similar between the two arms (53.41 vs. 46.59 months, HR [95% CI]: 1.18 [0.91-1.53], Wald’s p=0.211). Lower grade 3 or 4 neurotoxicity (1.9% vs. 10.8%, p< 0.001) but higher myelotoxicity (neutropenia 38.8% vs. 28.8%, p=0.031; thrombocytopenia 20% vs. 8.3%, p=0.004) was observed in the C8P4 arm. Conclusions: Lowering the total number of cycles of paclitaxel in 1st-line chemotherapy of advanced OC, FC, PPC resulted in similar OS but shorter median PFS and is not recommended in this setting. The reduction of neurotoxicity by limiting the total paclitaxel cycles to 4 is achieved at the expense of higher myelotoxicity.

Randomized multicenter phase III trial of oxaliplatin plus raltitrexed compared to oxaliplatin plus fluorouracil and leucovorin treatment in recurrent and metastatic colorectal cancer

2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 4102-4102
Author(s):  
J. Wang ◽  
J. Li ◽  
S. Qin ◽  
T. Liu ◽  
Z. Ye ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Disease Control ◽  
Metastatic Colorectal Cancer ◽  
Median Number ◽  
Disease Control Rate ◽  
Phase Iii ◽  
Progression Of Disease ◽  
Grade 3 ◽  
Number Of Cycles ◽  
Ecog Ps

4102 Purpose: To compare oxaliplatin (L-OHP) plus raltitrexed (RTX) with L-OHP plus fluorouracil and leucovorin (LV/5FU) for patients (pts) with recurrent and metastatic colorectal cancer(CRC). Methods: Eligible pts had to have histologically proven recurrent or metastatic CRC,not having previously received oxaliplatin as palliative chemotherapy,ECOG PS = 2,age:18∼70,and adequate hematological,renal and hepatic function.After written informed consent,pts were randomized to L-OHP:130 mg/m2 d1 + RTX: 3 mg/m2 d1 (Arm A) or + LV: 200 mg/m2 + 5FU:375 mg/m2 d1–5 (Arm B). Results: Between Jan 2005 and July 2006, 216 pts were enrolled at 15 centers in China.112 pts (mean age: 55.0 (19∼70), M/F: 57/46, PS 0/1/2: 46/53/13) were randomly assigned to A and 102 (mean age: 54.2(22∼70), M/F: 54/46, PS 0/1/2: 44/59/9) to B. 203 pts were eligible for response evaluation (A:103, B:100).The median number of cycles was 4 (1∼6) in A and 3 (1∼6) in B (P=0.1431).The RR was 29.1% (CR:2, PR:28, SD:50 , PD:23) in A and 17.0% (CR:2, PR:15, SD:46 , PD:37) in B (P=0.0437).The disease-control rate was 77.7% in A and 63.0% in B (P=0.0237). After a median follow-up of 10 months (4–16.5),92 pts had had progression of disease (40 in A and 52 in B); 73 deaths had occurred (35 in A and 38 in B), median time to progression was not reached. Following-up is ongoing.The median QoL scores for the two arms were comparable. 214 were included in the safety analyses (A:112, B:102). There was a higher incidence of neutropenia (48.2% verse 29.4%, P=0.005) and transaminase increase (49.1% verse 35.3%, P=0.041) among A. Grade 3 or 4 neutropenia was much common in pts in A than those in B (20.5% verse 4.9% , P=0.001), but was complicated by fever in only 3.6% of cases (4 pts) in A and in 2.9% of cases (3 pts) in B. No pts were dead or infectious due to neutropenia. There were similar rates of grade 3 or 4 transaminase elevation in the two groups. Vomitting and anorexia were much commoner with B. Conclusions: The L-OHP+RTX seems beneficial in recurrent and metastatic CRC, demonstrating better response rate and higher disease control rate with acceptable tolerability, maintenance of QoL and convenient administration schedule. No significant financial relationships to disclose.

Irinotecan versus best supportive care (BSC) as second-line therapy in gastric cancer: A randomized phase III study of the Arbeitsgemeinschaft Internistische Onkologie (AIO)

2009 ◽  
Vol 27 (15_suppl) ◽  
pp. 4540-4540 ◽  
Author(s):  
P. C. Thuss-Patience ◽  
A. Kretzschmar ◽  
T. Deist ◽  
A. Hinke ◽  
D. Bichev ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Overall Survival ◽  
Locally Advanced ◽  
Phase Iii ◽  
Open Label ◽  
Logrank Test ◽  
Line Therapy ◽  
Phase Iii Study ◽  
Ecog Ps ◽  
Line Chemotherapy

4540 Background: Up to now the value of 2nd-line therapy for metastatic gastric cancer is unclear. So far there are no randomized phase III data comparing 2nd-line chemotherapy to BSC. Irinotecan has proven activity in 1st-line therapy. In this randomized phase III study we compared irinotecan to BSC to evaluate the value of 2nd- line chemotherapy for gastric cancer. Methods: Prospective multicenter randomized phase III study, open label. Eligibility: Metastatic or locally advanced gastro-esophageal junction or gastric adenocarcinoma. Objective tumor progession (PD) within 6 months after 1st- line chemotherapy. ECOG PS 0–2. Statistics: Primary endpoint: Overall survival (OS). Hypothesis: H1: OS(Irinotecan)>OS(BSC). Calculated number of pts needed (power 80%, alpha error 5%): 60 pts per arm. Stratification for a) PD less versus (vs) more than 3 months after 1st line chemotherapy, b) ECOG PS 0/1 vs 2. Treatment: Arm A: Irinotecan 250mg/m2 q3w (1st cycle) to be increased to 350 mg/m2, depending on toxicity. Arm B: BSC Results: Between Oct 2002 and Dec 2006 40 pts were randomized. The study was closed prematurely due to poor accrual. Arm A:21 pts, arm B 19 pts. Median age A: 58 yrs (43–73), B: 55 yrs (35–72); PD less vs more than 3 months after 1st-line chemotherapy: A: 18 / 3, B: 17 / 2pts. ECOG PS 0/1 vs 2: A: 17/ 4, B: 14/ 5pts. Pre-treatment with cisplatin: A: 21, B:19 pts. Arm A: 68 cycles administered in 21 pts. Toxicity: (main CTC grade 3/ 4): Nausea 1 pt, vomiting 1 pt, diarrhoea: 5 pts, neutropenic fever: 2 pts, data incomplete 6 pts. In 37% of 19 evaluable pts irinotecan dose was escalated to 350mg/m2. Response (19 pts evaluable): No objective responses, SD 58%, PD 42%. Improvement of tumor related symptoms: 44% of pts in arm A, 5% in arm B. Survival: (evaluable pts arm A 21, arm B 18): median survival arm A: 123 days (95%CI 95–216), arm B 72.5 days (95%CI 41–106); OS: HR=2.85 (95%CI 1.41–5.79), Logrank test (two-sided): p=0.0027. Conclusions: To our knowledge this is the first randomized phase III study investigating 2nd- line chemotherapy in gastric cancer. Irinotecan as 2nd-line chemotherapy significantly prolongs overall survival compared to BSC. 2nd-line chemotherapy can now be considered as a proven option in gastric cancer. [Table: see text]

Phase II study of gemcitabine (Gem) + docetaxel (D) in combination with trastuzumab (T) in patients (pts) with HER2-overexpressing metastatic breast cancer (MBC)

2006 ◽  
Vol 24 (18_suppl) ◽  
pp. 10730-10730
Author(s):  
D. R. Fescina ◽  
W. Gradishar ◽  
M. Orlando ◽  
J. Rubinsak ◽  
L. Haney ◽  
...  
Keyword(s):  
Single Agent ◽  
Metastatic Breast ◽  
Dose Intensity ◽  
Progression Free Survival ◽  
Phase Iii ◽  
First Line Therapy ◽  
Metastatic Setting ◽  
Grade 3 ◽  
Number Of Cycles ◽  
Ecog Ps

10730 Background: Addition of T to chemotherapy (chemo) is assoc. with improved overall survival (OS) in pts with HER2+ tumors. Combination chemo has shown improvements in PFS and OS over single agent in recent phase III studies. Pre-clinical models suggest that the combination of G and D appears to be synergistic and that either agent is also synergistic with T. Objectives: This multi-institutional study was designed to determine overall RR (primary endpoint), TTP, OS and the toxicity profile of the combination of G + D + T as first-line therapy for MBC pts. Design: Pts with measurable HER2-overexpressing (FISH+) MBC, no prior chemo in the metastatic setting, adequate end-organ function and PS 0–2, received Gem 1,000 mg/m2 over 30 min on days 1 and 8 + D 75 mg/m2 day 1 and T on day 1 (8 mg/kg over 90 min on cycle 1, then 6 mg/kg over 30 min on subsequent cycles) of a 21-day cycle, until progressive disease or undue toxicity. Results: 8 pts have been enrolled over a period of 16 months. Median age: 53 years (range 40–74); ER status ±: 5/3 pts; ECOG PS 0 = 3 pts, 1 = 4 pts, 2 = 1 pt; Prior adjuvant therapy: Chemo ± Hormonal 3, Hormonal only 3, T 1. Sites of Disease: All pts had visceral involvement (Lung 4, Liver 5) and 5 pts ≥ 2 sites of metastatic disease. Total number of cycles administered was 52; median per pt. 7 (range 4–10). Median delivered dose intensity for G, D and T was 91%, 92% and 100% respectively. Toxicity was generally manageable. One pt discontinued therapy due to adverse events (grade 3 pneumonitis). Grade 3/4 neutropenia occurred in 27% and 10% of cycles; no grade 3/4 anemia or thrombocytopenia were recorded; Non-Heme toxicities of grade 2/3, included with dyspnea (0/2 pts), emesis (2/1), fatigue (4/1), diarrhea (1/1), dehydration (0/1), constipation (1/0). Complete alopecia was observed in 2 pts. No symptomatic cardiac toxicity was recorded. Best Overall RR assessment (N = 8): CR 3, PR 4, SD 1, PD 0, for an ORR of 7 out of 8 pts or 88% (95% CI: 47%–100%). Only 3 pts have progressed, and no pt has died. Progression-free survival at 1 year is 58%. Conclusion: According to this limited experience, the combination of G + D + T in front-line MBC is well tolerated and active. Study was discontinued due to slow accrual as of Feb 2004. Supported by Eli Lilly & Company. [Table: see text]

Phase III randomized study of vinorelbine (V), gemcitabine (G) followed by docetaxel (D) (VGD) versus paclitaxel (P) and carboplatin (C) (PC) in patients (pts) with advanced non-small cell lung cancer (NSCLC) (Japan Multinational Trial Organization LC00–03)

2006 ◽  
Vol 24 (18_suppl) ◽  
pp. 7013-7013
Author(s):  
M. Kawahara ◽  
M. Ogawara ◽  
Y. Nishiwaki ◽  
K. Kubota ◽  
K. Komuta ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Advanced Nsclc ◽  
Randomized Study ◽  
Stage Iv ◽  
Progression Free Survival ◽  
Stage Iiib ◽  
Phase Iii ◽  
Grade 3 ◽  
Level Of Significance ◽  
Ecog Ps

7013 Background: Our phase II study of non-platinum VGD for advanced NSCLC demonstrated excellent results with the median survival time (MST) of 15.7 mos and a 1-year survival rate of 59% (Brit J Cancer 88:42,2003). A phase III trial was performed to determine the survival benefit of VGD compared with PC for advanced NSCLC as a Japan-SWOG Lung Cancer Common Arm Trial. Methods: Between Mar 2001 and Apr 2005, 401 chemo-naïve NSCLC pts with Stage IIIB with pleural effusion or Stage IV without brain metastasis, who had ECOG PS 0–1, were randomized to VGD; V 25 mg/m2 iv and G 1000 mg/m2 iv, days 1, 8, every 21 days for 3 cycles followed by D 60 mg/m2 iv, d1, every 21 days for 3 cycles or PC; C AUC=6 iv and P 225 mg/m2 iv, day 1, every 21 days for 6 cycles. The primary endpoint was overall survival (OS). For a two-sided test at the 5% level of significance and power of 85%, the number of pts required to detect a 40% difference in MST was 400. Results: 393 pts (196 VGD, 197 PC) were evaluable for response, OS and toxicity. Baseline demographics were balanced (VGD vs PC): median age 65 yrs(both arms);male(74 vs 69%); PS 0 40%(both arms);Stage IIIB (17 vs 18%); Ad/Sq (66%/23% vs 76%/15%). There were 238 deaths with a median follow-up of 23 mos. 49% in VGD and 29% in PC arm completed 6 cycles (p=0.00005). Response rates in arms VGD/PC were 23% vs 36% (p= 0.008). There were no significant differences in progression free survival, OS, 1- and 2-yr survivals between VGD and PC arms: 5.9 vs 6.0 mos (p=0.95, Log rank), 13.1 vs 13.8 mos (MST, p=0.28, Log rank), 55.6 vs 55.5%, and 27.6 vs 31.8%. Grade 3/4 toxicities in arms VGD/PC were: neutropenia (G4) (30 vs 54%, p<0.00001), thrombocytopenia (4 vs 6%), febrile neutropenia (20 vs 19%), neuropathy (2 vs 21%, p<0.00001), pulmonary (9 vs 2%, p=0.0006). There were 2 treatment-related deaths (pneumonitis) in VGD arm. Conclusions: Non-platinum triplet chemotherapy had comparable activity in pts with advanced NSCLC. The VGD had significantly less myelosuppression, but more pulmonary toxicity than PC. No significant financial relationships to disclose.

Improving safety in first-line metastatic colorectal cancer (MCRC) therapy with bevacizumab: Modified FOLFOX7 versus XELOX2—Results of the induction phase of the GERCOR DREAM randomized phase III study.

2015 ◽  
Vol 33 (3_suppl) ◽  
pp. 670-670 ◽  
Author(s):  
Christophe Tournigand ◽  
Benoist Chibaudel ◽  
Benoit Samson ◽  
Werner Scheithauer ◽  
Gérard Lledo ◽  
...  
Keyword(s):  
Performance Status ◽  
Phase Iii ◽  
Induction Phase ◽  
First Line ◽  
Study Results ◽  
Phase Iii Study ◽  
Grade 3 ◽  
Reduced Toxicity ◽  
Metastatic Sites ◽  
Ecog Ps

670 Background: FOLFOX7 is an oxaliplatin FOLFOX regimen without 5FU bolus, first used in the OPTIMOX1 MCRC study (Tournigand, JCO 2006). Modified (m) FOLFOX7 has a reduced dose of oxaliplatin (100 mg/m²) and has been used in the OPTIMOX2 trial (Chibaudel, JCO 2009). XELOX2 derived from the bi-weekly XELOX regimen with oxaliplatin 85 mg/m² (Scheithauer, JCO 2003). Methods: First-line induction therapy (IT) allocation was randomized in unresectable MCRC patients with performance status (PS) 0-1 between 6 cycles of mFOLFOX7 with bevacizumab (B) or 6 cycles of XELOX2 with B. Stratification criteria were: center, age, ECOG PS, number of metastatic sites and LDH level. After 3-month IT, a second randomization for maintenance therapy allocation was done in non-progressive patients between B or B-erlotinib. mFOLFOX7-B consisted in B 5 mg/kg followed by folinic acid (FA) 400 mg/m² and oxaliplatin 100 mg/m² followed by 5-flurouracil (5FU) 2,400 mg/m² 46h-infusion. XELOX2-B consisted in B 5 mg/kg followed by oxaliplatin 100 mg/m² followed by capecitabine 1,250 mg/m² twice daily for seven days. Cycles were repeated every two weeks. The objective was to compare the safety and efficacy of XELOX2-B to mFOLFOX7-B (secondary objective of the study). Results: 156 patients were randomized to mFOLFOX7-B and 154 to XELOX2-B. Medians (mFOLFOX7/XELOX2) were: PFS 7.9/8.7 months (HR 0.98, CI 0.74-1.31; p=0.918), OS 26.6/23.4 months (HR 1.24, CI 0.98-1.59; p=0.075). RR (mFOLFOX7/XELOX2) was 50.0%/49.3%. Main grade 3/4 toxicities (mFOLFOX7/XELOX2) were neutropenia 9.2%/2.6% (p=0.018), diarrhea 5.2%/18.3% (p<0.001), asthenia 2.6%/11.8% (p=0.003), all 27.5%/37.6% (p=0.068). Conclusions: Both regimens have the same activity as the parent regimens with a reduced toxicity, especially mFOLFOX7-B. These regimens could be good backbones for future combinations with other agents and are well suited for frail and elderly patients. Clinical trial information: NCT00265824.

Topotecan Compared With No Therapy After Response to Surgery and Carboplatin/Paclitaxel in Patients With Ovarian Cancer: Multicenter Italian Trials in Ovarian Cancer (MITO-1) Randomized Study

2004 ◽  
Vol 22 (13) ◽  
pp. 2635-2642 ◽  
Author(s):  
Sabino De Placido ◽  
Giovanni Scambia ◽  
Giovanni Di Vagno ◽  
Emanuele Naglieri ◽  
Alessandra Vernaglia Lombardi ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Residual Disease ◽  
Randomized Study ◽  
Advanced Ovarian Cancer ◽  
Stage Iv ◽  
Progression Free Survival ◽  
Phase Iii ◽  
Rank Test ◽  
Significant Difference ◽  
Grade 3

Purpose Topotecan is an active second-line treatment for advanced ovarian cancer. Its efficacy as consolidation treatment after first-line standard chemotherapy is unknown. Patients and Methods To investigate whether topotecan (1.5 mg/m2 on days 1 through 5, four cycles, every 3 weeks) prolonged progression-free survival (PFS) for patients responding to standard carboplatin (area under the curve 5) and paclitaxel (175 mg/m2 administered as a 3-hour infusion in six cycles; CP), a multicenter phase III study was performed with an 80% power to detect a 50% prolongation of median PFS. Patients were registered at diagnosis and randomized after the end of CP. Results Two hundred seventy-three patients were randomly assigned (topotecan, n = 137; observation, n = 136), with a median age of 56 years. Stage at diagnosis was advanced in three fourths of patients (stage III in 65% of patients; stage IV in 10%); after primary surgery, 46% had no residual disease and 20% were optimally debulked. After CP, 87% reached a clinical complete response, and 13% achieved a partial response. Neutropenia (grade 3/4 in 58% of the patients) and thrombocytopenia (grade 3 in 21%; grade 4 in 3%) were the most frequent toxicities attributed to topotecan. There was no statistically significant difference in PFS between the arms (P = .83; log-rank test): median PFS was 18.2 months in the topotecan arm and 28.4 in the control arm. Hazard ratio of progression for patients receiving topotecan was 1.18 (95% CI, 0.86 to 1.63) after adjustment for residual disease, interval debulking surgery, and response to CP. Conclusion The present analysis indicates that consolidation with topotecan does not improve PFS for patients with advanced ovarian cancer who respond to initial chemotherapy with carboplatin and paclitaxel.

First-line gefitinib versus first-line chemotherapy by carboplatin (CBDCA) plus paclitaxel (TXL) in non-small cell lung cancer (NSCLC) patients (pts) with EGFR mutations: A phase III study (002) by North East Japan Gefitinib Study Group

2009 ◽  
Vol 27 (15_suppl) ◽  
pp. 8016-8016
Author(s):  
K. Kobayashi ◽  
A. Inoue ◽  
M. Maemondo ◽  
S. Sugawara ◽  
H. Isobe ◽  
...  
Keyword(s):  
Stage Iv ◽  
Progression Free Survival ◽  
Phase Iii ◽  
Egfr Mutations ◽  
First Line ◽  
North East ◽  
Phase Ii Studies ◽  
Grade 3 ◽  
Ecog Ps ◽  
Line Chemotherapy

8016 Background: Based on our promising results of phase II studies estimating gefitinib in NSCLC pts with sensitive EGFR mutations (JCO 2006, BJC 2006), this multicenter phase III trial compared progression free survival (PFS) of first line gefitinib versus first line chemotherapy in EGFR mutation positive pts with stage IIIB/IV NSCLC. Per protocol, an analysis for safety except response, PFS and overall survival were estimated. Methods: PNA-LNA PCR clamp test, which had been developed and validated by us (Cancer Res 2005, Cancer Sci 2007), was employed to detect EGFR mutations using cytological samples or histological samples. Pts having sensitive EGFR mutations, measurable site(s), ECOG PS 0–1, age of 20–75 years, and no prior chemotherapy were randomized (1:1 ratio; balanced for institution, sex, and stage) to receive Arm A: gefitinb (250 mg/ day) orally, or Arms B: CBDCA AUC 6 and TXL 200mg/m2 in 21-day cycles until disease progression. The primary endpoint was PFS, and the sample size was calculated to be 320 in total (alpha=5%, power=80%) to confirm the superiority of Arm A (hazard ratio = 0.69). Results: From April 2006 to July 2008, 155 pts were enrolled (Arm A=80; Arm B=75). Their characteristics were well balanced between arms: median age=65 years; 64% female; 77% Stage IV; 93% adenocarcinoma, 61% non-smoker. There were several differences in toxicities between Arm A and Arm B (grade 4 neutropenia: 1% vs. 29%, grade 3–4 liver dysfunction: 24% vs. 1%, grade 3 neuropathy: 0% vs. 5%, respectively, p<0.01). But these were tolerable in both arms. Furthermore, there were no interstitial lung disease and no toxic deaths in both arms. Analyzing both arms together, preliminary response rate and PFS of the 155 pts were 53.7% and 6.5 mos, respectively. Conclusions: This is the first prospective study to compare first line gefitinib with first line chemotherapy for advanced NSCLC pts harboring EGFR mutations. Due to acceptable toxicities, the independent safety committee decided to continue this study further. At the end of 2008, 200 pts have been entered to this study, and, per protocol, an interim analysis to investigate PFS will be performed in May 2009. No significant financial relationships to disclose.

A randomized phase III study of gemcitabine (GEM) versus pegylated liposomal doxorubicin (PLD) in progressive/recurrent ovarian cancer (OC)

2007 ◽  
Vol 25 (18_suppl) ◽  
pp. LBA5506-LBA5506 ◽  
Author(s):  
G. Ferrandina ◽  
D. Lorusso ◽  
S. Pignata ◽  
E. Breda ◽  
A. Savarese ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Pegylated Liposomal Doxorubicin ◽  
Recurrent Ovarian Cancer ◽  
Primary Treatment ◽  
Phase Iii ◽  
Hematological Toxicity ◽  
P Value ◽  
Phase Iii Study ◽  
Grade 3 ◽  
Number Of Cycles

LBA5506 Background: This multi-center Phase III study was designed to compare the efficacy and safety of PLD vs GEM in ovarian cancer (OC) patients relapsing within 12 months from platinum/paclitaxel treatment. Methods: Recurrent OC patients failing only one line of platinum/paclitaxel regimen with a platinum-free interval (PFI) ≤12 months, and with measurable or evaluable disease were eligible. Patients were randomized to receive PLD 40 mg/m2 d1 over 1 hr q 4 wk versus GEM 1,000 mg/m2 d1,8,15 over 30 min q 4 wk. The primary endpoint was time to progression (TTP), with overall survival (OS), overall response rate (ORR), safety/toxicity, and quality of life (QoL) as secondary endpoints. A total of 147 patients was calculated to be required (alpha=0.05, beta=0.80) in order to detect an increase in median TTP from 12 to 19 weeks in control (PLD) versus experimental (GEM) arm. Results: As of December 2006, 147 patients were enrolled; 74 and 73 patients were randomized to PLD versus GEM, respectively: overall, median age was 65 yrs (range 28–80); 69 (46.9%) patients had a PFI < 6 months, while 78 (53.1%) had a PFI between 6–12 months. response evaluation was possible in 129 cases: in PLD arm, the ORR was 15.9%, compared to an ORR=28.3% in GEM arm, p value=0.13). With a median follow up of 9 months, there was no difference in TTP between PLD and GEM arms (median TTP=16 versus 20 weeks, respectively; p value=0.44). Median OS was 56 weeks in PLD patients versus 50 weeks in GEM arm (p value=0.17). Total number of cycles was 301 in PLD arm, and 275 in GEM arm. Grade 3–4 leukopenia was documented in 8.7% of patients allocated to PLD versus 22.0% of patients administered GEM (p value=0.03); no difference in the distribution of severe anemia and thrombocytopenia was observed. There was no difference in non hematological toxicity. A total of 121 patients were considered for QoL data analysis: a trend to a better global QoL score was documented in PLD arm. (p value=0.015) Conclusions: PLD and GEM show similar activity in OC recurring within 12 months from primary treatment. No significant financial relationships to disclose.

First-line carboplatin, pemetrexed, and panitumumab in patients with advanced nonsquamous KRAS wild type (WT) non-small cell lung cancer (NSCLC).

2013 ◽  
Vol 31 (15_suppl) ◽  
pp. 8062-8062 ◽  
Author(s):  
Tarek Mekhail ◽  
David Michael Waterhouse ◽  
Terence J. Hadley ◽  
Charles D. Webb ◽  
Howard A. Burris ◽  
...  
Keyword(s):  
Median Number ◽  
Phase Iii ◽  
First Line ◽  
Unresectable Stage ◽  
Grade 3 ◽  
Number Of Cycles ◽  
Ecog Ps ◽  
Unacceptable Toxicity ◽  
Severe Grade

8062 Background: KRAS WT colorectal cancer (CRC) is responsive to the EGFR inhibitors panitumumab (P) and cetuximab. Phase III data suggest a small, but statistically significant overall survival (OS) advantage with cetuximab + chemotherapy in KRAS unselected NSCLC (Pirker, Lancet 2009); and phase I data suggest P alone has activity in non-CRC tumors including NSCLC (Weiner, Clin Ca Res. 2008). This single-arm phase II trial examined the safety and efficacy of P in combination with carboplatin (C) and pemetrexed (Pem) in patients (pts) with advanced non-squamous KRAS WT NSCLC. The addition of P was hypothesized to improve the median time-to-progression (TTP) from 3.6 months (mos) (historical) to 5.4 mos (1-sided α .10, 80% power). Methods: Pts with previously untreated, unresectable stage IIIB/IV non squamous KRAS WT NSCLC received P 9 mg/kg, Pem 500 mg/m2, and C AUC=6 IV day 1 every 21 days for 6 cycles, followed by P and Pem maintenance every 21 days until progressive disease or unacceptable toxicity. Responses were evaluated every 2 cycles per RECIST 1.1. KRAS mutation testing was performed centrally (DxS kit). Tissue was also collected for EGFR FISH testing. Results: 60 pts were enrolled; median age, 65 years; 58% female, ECOG PS 0-1 (98%), and prior adjuvant chemotherapy (10%). Median number of cycles was 5 (range 1-22). At a median follow-up of 8.7 mos, the median TTP was 6.2 mos (95% CI: 3.7, 9.5), PFS 6.2 mos (95% CI 3.0, 9.0), 1 year OS 65.5% (95% CI 44.8%, 80%). 23 pts (38%) had partial responses (PR); the disease control rate (PR + proportion with stable disease) was 68%. Treatment-related toxicity (TRT) included (all grades) nausea (38%), fatigue (30%), rash (30%), and mucositis (23%). Severe (grade 3/4) TRT in > 2 pts included: thrombocytopenia (11%), neutropenia (7%), and dehydration (5%). There were no treatment-related deaths. EGFR mutation and FISH analyses will be presented. Conclusions: The addition of panitumumab to carboplatin and pemetrexed in the first-line treatment of advanced KRAS WT NSCLC was safe and well-tolerated; the median TTP of 6.2 mos met the primary endpoint. Definitive assessment of the value of panitumumab in this setting requires a randomized trial. Clinical trial information: NCT01042288.

A phase III study of pemetrexed (Pem) plus carboplatin (Cb) plus bevacizumab (Bev) followed by maintenance pem plus bev versus paclitaxel (Pac) plus cb plus bev followed by maintenance bev in stage IIIb or IV nonsquamous non-small cell lung cancer (NS-NSCLC): Overall and age group results.

2013 ◽  
Vol 31 (15_suppl) ◽  
pp. 8004-8004 ◽  
Author(s):  
Mark A. Socinski ◽  
Jyoti D. Patel ◽  
Edward B. Garon ◽  
Ramaswamy Govindan ◽  
Craig H. Reynolds ◽  
...  
Keyword(s):  
Type I Error ◽  
Safety Data ◽  
Sensory Neuropathy ◽  
Progression Free Survival ◽  
Phase Iii ◽  
Type I ◽  
Cox Models ◽  
Phase Iii Study ◽  
Grade 3 ◽  
Ecog Ps

8004 Background: This study compared Pem+Cb+Bev followed by Pem+Bev maintenance (Pem arm) to Pac+Cb+Bev followed by Bev maintenance (Pac arm). The primary endpoint of improved overall survival (OS) for the Pem arm was not met. Methods: Advanced NS-NSCLC pts, ECOG PS 0/1, were randomized to 4 cycles of induction Pem+Cb+Bev with folic acid+vitamin B12 or Pac+Cb+Bev (Pem 500 mg/m2or Pac 200 mg/m2; Cb AUC 6; Bev 15 mg/kg) every 3 weeks. Eligible pts received maintenance Pem+Bev or Bev. OS, progression-free survival (PFS), overall response (ORR), and toxicity were evaluated. A hazard ratio (HR) of 0.80 required 676 OS events/900 pts with 2-sided type-I error .05 and at least 80% power for superiority of Pem over Pac arm. Exploratory Cox models estimated treatment HRs with 95% confidence intervals (CIs) for each age subgroup analyzed: ≤ or >65, 70 (prespecified) and ≤ or >75 yrs (not prespecified). Results: 939 pts (median age, 64.7) were randomized. Median (m) OS for ITT pem and pac arms was 12.6 vs 13.4 mos (HR 1.00, p=0.949); mPFS was 6.0 vs 5.6 mos (HR 0.83, p=0.012) Subgroup efficacy is shown in the Table; ≤ or >65 data were similar to ITT. Pem pts had significantly more drug-related grade 3/4 thrombocytopenia, anemia (except >75 yrs) and fatigue (except >70 and >75 yrs). Pac pts had significantly more grade 3/4 neutropenia (except >70 and >75 yrs), sensory neuropathy (except >75 yrs) and grade 1/2 alopecia. Results parallel overall safety data. Conclusions: OS was not significantly different in any of the age subgroups. PFS was significantly longer in Pem arm overall and for pts ≤70, but was similar for pts >70, >75 yrs. Toxicity profiles differed; subgroup safety data paralleled overall data. Clinical trial information: NCT00762034. [Table: see text]

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