scholarly journals Randomized, Phase II Study Prospectively Evaluating Treatment of Metastatic Esophageal, Gastric, or Gastroesophageal Cancer by Gene Expression of ERCC1: SWOG S1201

2020 ◽  
Vol 38 (5) ◽  
pp. 472-479 ◽  
Author(s):  
Syma Iqbal ◽  
Shannon McDonough ◽  
Heinz-Josef Lenz ◽  
David Ilson ◽  
Barbara Burtness ◽  
...  
Keyword(s):  
Mrna Expression ◽  
Phase Ii ◽  
Phase Ii Study ◽  
Performance Status ◽  
Interactive Effects ◽  
Randomized Phase Ii ◽  
Esophagogastric Cancer ◽  
Significant Difference ◽  
Grade 3 ◽  
Ercc1 Expression

PURPOSE Platinum-based therapy is the standard of care in patients who have HER2-negative, advanced esophagogastric cancer (AEGC). Retrospective data suggest that intratumoral ERCC1 levels may determine platinum sensitivity. A randomized, phase II study was performed in patients with AEGC to explore whether the efficacy of a platinum-based therapy with fluorouracil, leucovorin, and oxaliplatin (FOLFOX) versus a non–platinum-containing regimen of irinotecan and docetaxel (IT) differed according to ERCC1 levels. PATIENTS AND METHODS Overall, 202 untreated patients with HER2-negative AEGC and a Zubrod performance status of 0-1 were evaluated prospectively for mRNA expression of ERCC1 level and then randomly assigned to FOLFOX or IT, stratified by the intratumoral statuses of ERCC1 low (< 1.7) or high (≥ 1.7). Objectives were to assess progression-free survival (PFS) and overall survival (OS) in all patients treated with FOLFOX compared with IT, stratified by low and high ERCC1 levels, and to assess for interactive effects between ERCC1 expression and treatment arm. RESULTS Eighty-six percent of patients had ERCC1 values < 1.7. Thus, evaluation of the ERCC1-high subgroup was limited. Grade ≥ 3 anemia, dehydration, diarrhea, and fatigue were greater in patients with IT. Occurrences of grade ≥ 3 neuropathy and decreased neutrophils were greater in patients with FOLFOX. In all patients, FOLFOX had a statistically superior median PFS compared with IT (5.7 v 2.9 months; hazard ratio, 0.68; P = .02). In patients with ERCC1 levels < 1.7 receiving FOLFOX, PFS and response rate were statistically superior to IT, with no significant difference in OS. CONCLUSION The evaluation of ERCC1 in patients with upper GI tumors was thwarted by an overwhelming predominance of low ERCC1 mRNA expression. Nonetheless, distribution of treatment effects on PFS did not vary with expression. For all patients and for those with low ERCC1 expression, FOLFOX was superior in efficacy to IT.

A randomized phase II pilot study prospectively evaluating treatment for patients based on ERCC1 for advanced/ metastatic esophageal, gastric, or gastroesophageal junction cancer: SWOG S1201.

2017 ◽  
Vol 35 (15_suppl) ◽  
pp. 4009-4009 ◽  
Author(s):  
Syma Iqbal ◽  
Shannon McDonough ◽  
Heinz-Josef Lenz ◽  
David H. Ilson ◽  
Barbara Burtness ◽  
...  
Keyword(s):  
Phase Ii ◽  
Phase Ii Study ◽  
Gastroesophageal Junction ◽  
Interactive Effects ◽  
Gastroesophageal Junction Cancer ◽  
Randomized Phase Ii ◽  
Esophagogastric Cancer ◽  
Grade 3 ◽  
Ercc1 Expression ◽  
Clinical Trial Information

4009 Background: Platinum based treatment (tx) is standard in HER2 negative patients (pts) with advanced esophagogastric cancer (AEGC). Retrospective data suggest intratumoral ERCC1 levels may determine platinum sensitivity. A randomized phase II study was performed in pts with AEGC to explore whether the efficacy of a platinum 5-FU/LV/Oxaliplatin (FOLFOX) vs. non-platinum containing regimen irinotecan/taxotere (IT) differed according to ERCC1 levels. Methods: 203 untreated pts with AEGC, Her2 -, Zubrod PS 0-1, were randomized to FOLFOX vs. IT, stratified by intratumoral ERCC1 low (<1.7) vs. high (≥1.7). Objectives were to assess PFS and OS in all pts treated with FOLFOX compared with IT, and in those pts with low and high ERCC1 levels and to assess for interactive effects between ERCC1 expression and tx arm. Results: 86% of pts had ERCC1 values <1.7. Thus, evaluation of ERCC1 pts in the high subgroup was not feasible. Tx groups were well matched by age, sex, race, ERCC1 level, and site. A series of K-M plots were used to explore whether tx arm differences in PFS varied based on ERCC1 levels; little evidence of such was noted. Grade ≥ 3 anemia, dehydration, diarrhea and fatigue were greater in pts with IT. Grade ≥ 3 neuropathy and decreased neutrophils were greater in pts with FOLFOX. Conclusions: In all pts, FOLFOX had a statistically superior PFS and RR, when compared with IT. In pts with ERCC1 <1.7 receiving FOLFOX, PFS and RR was statistically superior, with no difference in OS. There was no significant evidence of differential treatment effect on PFS across ERCC1 levels. Clinical trial information: NCT01498289. [Table: see text]

Oxaliplatin or Paclitaxel in Patients With Platinum-Pretreated Advanced Ovarian Cancer: A Randomized Phase II Study of the European Organization for Research and Treatment of Cancer Gynecology Group

2000 ◽  
Vol 18 (6) ◽  
pp. 1193-1202 ◽  
Author(s):  
Martine J. Piccart ◽  
John A. Green ◽  
Angel Jimenez Lacave ◽  
Nick Reed ◽  
Ignace Vergote ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Phase Ii ◽  
Phase Ii Study ◽  
Performance Status ◽  
Single Agent ◽  
Advanced Ovarian Cancer ◽  
Time To Progression ◽  
European Organization ◽  
Randomized Phase Ii ◽  
Grade 3

PURPOSE: This was a multicentric, open, randomized, phase II study of single-agent paclitaxel and oxaliplatin to evaluate the efficacy of oxaliplatin in a relapsing progressive ovarian cancer patient population and to analyze the safety profile and impact of both agents on quality of life, time to progression, and survival. PATIENTS AND METHODS: Eighty-six patients with platinum-pretreated advanced ovarian cancer were randomly assigned to two arms: 41 received paclitaxel at 175 mg/m2 over 3 hours every 3 weeks, and 45 received oxaliplatin at 130 mg/m2 over 2 hours every 3 weeks. For inclusion, patients had to have a performance status of 0 to 2 and to have received at least one and no more than two prior cisplatin- and/or carboplatin-containing chemotherapy regimens within the last 12 months. RESULTS: Seven confirmed responses were observed in each arm, for an overall response rate in the total treated population of 17% (95% confidence interval [CI], 7% to 32%) in the paclitaxel arm and 16% (95% CI, 7% to 29%) in the oxaliplatin arm. Median time to progression was 14 weeks and 12 weeks, and overall survival was 37 weeks and 42 weeks in the paclitaxel and oxaliplatin arms, respectively. Among 63 patients with a 0- to 6-month progression-free, platinum-free interval, there were five objective responses with paclitaxel in 31 patients and two objective responses with oxaliplatin in 32 patients. Nine patients (22%) in the paclitaxel arm had grade 3 or 4 neutropenia (National Cancer Institute of Canada [NCIC] Common Toxicity Criteria). Two patients (4%) experienced grade 3 thrombocytopenia in the oxaliplatin arm. Maximum grade (grade 3) NCIC neurosensory toxicity was experienced by three patients (7%) in the paclitaxel arm and by four patients (9%) in the oxaliplatin arm. CONCLUSION: Single-agent oxaliplatin at 130 mg/m2 every 3 weeks is active with moderate toxicity in patients with cisplatin-/carboplatin-pretreated advanced ovarian cancer.

Biomarker distribution and characteristics for the first 100 patients in MAVERICC, a randomized phase II study of mFOLFOX6-bevacizumab (BV) versus FOLFIRI-BV in previously untreated metastatic colorectal cancer (mCRC).

2013 ◽  
Vol 31 (4_suppl) ◽  
pp. 483-483
Author(s):  
Alexander Starodub ◽  
Sachdev P. Thomas ◽  
Fa-Chyi Lee ◽  
Vallathucherry Harish ◽  
Han A. Koh ◽  
...  
Keyword(s):  
Mrna Expression ◽  
Phase Ii ◽  
Phase Ii Study ◽  
Progression Free Survival ◽  
Metastatic Lesion ◽  
Metastatic Colon Cancer ◽  
Open Label ◽  
Randomized Phase Ii ◽  
Open Label Phase ◽  
Ercc1 Expression

483^ Background: Retrospective analyses have suggested that ERCC1 is a chemo-resistance marker to platinum compounds; a median tumoral ERCC1 level of 1.7 × 10–3ERCC1/β-actin mRNA has been reported in metastatic colon cancer (Grimminger et al, Pharmacogenomics J, 2011). MAVERICC is the first prospective study of tumoral ERCC1and plasma VEGF-A as potential biomarkers for oxaliplatin- and BV-containing regimens, respectively. We present data from a planned interim biomarker distribution assessment of the first 100 patients (pts) in MAVERICC. Methods: In this randomized, open-label, phase II study, pts (N=360) with histologically or cytologically confirmed CRC and ≥1 measurable metastatic lesion are stratified at screening by tumoral ERCC1 mRNA expression (low vs high, cutoff of ≤ vs >1.7). Stratified pts are randomized 1:1 to mFOLFOX6-BV or FOLFIRI-BV administered in 2-week cycles. The primary objectives are: 1) to assess ERCC1 and VEGF-A as biomarkers of progression-free survival (PFS) for oxaliplatin- and BV-containing 1st-line regimens, and 2) within ERCC1 high pts, to test whether FOLFIRI-BV is associated with a prolonged 1st-line PFS vs mFOLFOX6-BV. Results: With a data cutoff of June 19 2012, 100 pts have been enrolled. Of these, 75 pts were stratified to the ERCC1 high group and 25 pts to the ERCC1 low group. The median ERCC1 mRNA expression was 3.00 (range, 1.73–13.16) and 1.32 (range, 0.70–1.70) in the ERCC1 high and low stratification groups, respectively. Among all pts, the median ERCC1 mRNA expression was 2.37. Pt demographics by group are shown (Table). Plasma VEGF-A evaluation is ongoing. Conclusions: An analysis of the first 100 pts in MAVERICC showed that the median tumoral ERCC1 expression level was higher than the predefined cutoff, providing an adequate population of ERCC1 high pts to assess PFS by treatment regimen. Clinical trial information: NCT01374425. [Table: see text]

A randomized phase II study of continuous versus intermittent S-1 plus oxaliplatin in first-line treatment of patients with metastatic gastric carcinoma.

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. 4028-4028 ◽  
Author(s):  
Sook Ryun Park ◽  
Young-Iee Park ◽  
Jiyoung Rhee ◽  
Byung-Ho Nam ◽  
Sun-Young Kong ◽  
...  
Keyword(s):  
Phase Ii ◽  
Phase Ii Study ◽  
Progression Free Survival ◽  
Metastatic Gastric Cancer ◽  
Induction Treatment ◽  
Hematologic Toxicity ◽  
Randomized Phase Ii ◽  
Significant Difference ◽  
Grade 3 ◽  
Ecog Ps

4028 Background: We conducted a randomized phase II study to compare continuous vs. intermittent S-1 + oxaliplatin (SOX) after induction of 6 cycles of SOX in patients (pts) with metastatic gastric cancer (MGC). Methods: Pts >18 yrs with chemo-naive MGC, normal organ function, ECOG PS 0-2, and measurable or evaluable lesion(s) were initially given an induction treatment of 6 cycles of SOX (S-1 40 mg/m2 bid on D1-14 + oxaliplatin 130 mg/m2 on D1 q 3 wks). Pts with CR/PR or SD were randomized to continue SOX (arm A) until progression/intolerable toxicity or discontinue until progression when SOX was re-administered (arm B). The primary endpoint was overall survival (OS), and secondary endpoints included progression-free survival (PFS), response rate, safety, quality of life, and biomarker correlative studies. Results: From July 2007 to Dec 2010, a total of 250 pts entered into the study. Median age was 53 yrs (range, 24-69); PS 0/1/2=13/219/18; M/F=162/88. Three pts did not receive treatment and 126 (50.4%) discontinued treatment before or at the completion of 6 cycles of SOX due to progression (45.6%), pt refusal (2.8%), or adverse events (2.0%). A total of 121 pts were randomized: 59 (48.8%) to arm A and 62 (51.2%) to arm B. Clinical characteristics were well balanced between arms. SOX continuation resulted in a significant reduction in the risk of progression (median PFS, 10.5 months for arm A vs. 7.2 months for arm B; HR=0.57, 95% CI 0.39-0.84, p=0.005). With a median follow-up of 34.0 months (range, 10.5-53.3 months), there was no significant difference in OS (median OS, 22.6 months for arm A vs. 22.7 months for arm B; HR, 0.79, 95% CI 0.51-1.25, p=0.31). Arm A had higher rates of grade 3/4 fatigue (28.8% vs. 8.1%, p=0.004) and neuropathy (25.4% vs. 8.1%, p=0.014) but other grade 3/4 hematologic (neutropenia, 35.6% vs. 32.3%; thrombocytopenia, 23.7% vs. 21.0%; anemia, 15.3% vs. 6.5%) or non-hematologic toxicity rates were not significantly different. Conclusions: Continuous chemotherapy with SOX after induction therapy improved PFS but not OS. Supported by NCC Grant 1010180 (S-1 and oxaliplatin was provided by JEIL Pharm. Co., Ltd. and sanofi-aventis Korea Co., Ltd., respectively).

Phase II study of docetaxel and cisplatin in advanced non-small-cell lung cancer.

1998 ◽  
Vol 16 (5) ◽  
pp. 1948-1953 ◽  
Author(s):  
J Zalcberg ◽  
M Millward ◽  
J Bishop ◽  
M McKeage ◽  
A Zimet ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Phase Ii ◽  
Advanced Nsclc ◽  
Response Rate ◽  
Phase Ii Study ◽  
Performance Status ◽  
Objective Response ◽  
Small Cell ◽  
Small Cell Lung ◽  
Grade 3

PURPOSE Docetaxel (Taxotere, Rhone-Poulenc Rorer, Antony, France) and cisplatin are two of the most active single agents used in the treatment of non-small-cell lung cancer (NSCLC). A recently reported phase I study of the combination of docetaxel and cisplatin recommended a dose of 75 mg/m2 of both drugs every 3 weeks for subsequent phase II study. PATIENTS AND METHODS Eligible patients were aged 18 to 75 years with a World Health Organization (WHO) performance status < or = 2 and life expectancy > or = 12 weeks, with metastatic and/or locally advanced NSCLC proven histologically or cytologically. Patients were not permitted to have received prior chemotherapy, extensive radiotherapy, or any radiotherapy to the target lesion and must have had measurable disease. Concurrent treatment with colony-stimulating factors (CSFs) or prophylactic antibiotics was not permitted. Docetaxel (75 mg/m2) in 250 mL 5% dextrose was given intravenously (i.v.) over 1 hour immediately before cisplatin (75 mg/m2) in 500 mL normal saline given i.v. over 1 hour in 3-week cycles. Premedication included ondansetron, dexamethasone, promethazine, and standard hyperhydration with magnesium supplementation. RESULTS A total of 47 patients, two thirds of whom had metastatic disease, were entered onto this phase II study. The majority of patients were male (72%) and of good (WHO 0 to 1) performance status (85%). All 47 patients were assessable for toxicity and 36 were for response. Three patients were ineligible and eight (17%) discontinued treatment because of significant toxicity. In assessable patients, the overall objective response rate was 38.9% (95% confidence limits [CL], 23.1% to 56.5%), 36.1% had stable disease, and 25% progressive disease. On an intention-to-treat analysis, the objective response rate was 29.8%. Median survival was 9.6 months and estimated 1-year survival was 33%. Significant (grade 3/4) toxicities included nausea (26%), hypotension (15%), diarrhea (13%), and dyspnea mainly related to chest infection (13%). One patient experienced National Cancer Institute (NCI) grade 3 neurosensory toxicity after eight cycles. Grade 3/4 neutropenia was common and occurred in 87% of patients, but thrombocytopenia > or = grade 3 was rare (one patient). Significant (grade 3/4) abnormalities of magnesium levels were common (24%). Febrile neutropenia occurred in 13% of patients and neutropenic infection in 11%, contributing to two treatment-related deaths. No neutropenic enterocolitis or severe fluid retention was reported. CONCLUSION Compared with other active regimens used in this setting, the combination of docetaxel and cisplatin in advanced NSCLC is an active regimen with a similar toxicity profile to other combination regimens.

Randomized Multicenter Phase II Study Comparing a Combination of Fluorouracil and Folinic Acid and Alternating Irinotecan and Oxaliplatin With Oxaliplatin and Irinotecan in Fluorouracil-Pretreated Metastatic Colorectal Cancer Patients

2001 ◽  
Vol 19 (22) ◽  
pp. 4195-4201 ◽  
Author(s):  
Yves Bécouarn ◽  
Erick Gamelin ◽  
Bruno Coudert ◽  
Sylvie Négrier ◽  
Jean-Yves Pierga ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Folinic Acid ◽  
Phase Ii ◽  
Phase Ii Study ◽  
Survival Times ◽  
Activity Data ◽  
Randomized Phase Ii ◽  
Grade 3 ◽  
Intent To Treat ◽  
Colorectal Cancer Patients

PURPOSE: To assess antitumor activity and safety of two regimens in advanced colorectal cancer (CRC) patients with proven fluorouracil (5-FU) resistance in a randomized phase II study: 5-FU/folinic acid (FA) combined with alternating irinotecan (also called CPT-11) and oxaliplatin (FC/FO tritherapy), and an oxaliplatin/irinotecan (OC) combination. PATIENTS AND METHODS: Sixty-two patients were treated: arm FC/FO (32 patients) received, every 4 weeks, FA 200 mg/m2 followed by a 400-mg/m2 5-FU bolus injection, then a 600-mg/m2 continuous infusion of 5-FU on days 1 and 2 every 2 weeks administered alternately with irinotecan (180 mg/m2 on day 1) and oxaliplatin (85 mg/m2 on day 15). Arm OC (30 patients) received oxaliplatin 85 mg/m2 and irinotecan 200 mg/m2 every 3 weeks. RESULTS: In an intent-to-treat analysis, two partial responses lasting 10.7 and 16 months were observed with the tritherapy regimen, and seven (median duration, 11 months; range, 10.6 to 11.4 months) were observed with the bitherapy regimen. Median progression-free and overall survival times were 8.2 and 9.8 months, respectively, in the FC/FO arm and 8.5 and 12.3 months, respectively, in the OC arm. Main grade 3/4 toxicities were, respectively, neutropenia, 53% and 47%; febrile neutropenia, 13% and 3%; diarrhea, 19% and 10%; vomiting, 6% and 13%; and neurosensory toxicity, 3% and 3%. No treatment-related deaths occurred. CONCLUSION: The every-3-weeks OC combination is safe and active in advanced 5-FU–resistant CRC patients. The lower activity data seen with the tritherapy regimen may be related to the lower dose intensities of irinotecan and oxaliplatin in this schedule.

Long-Term Follow Up Of a Randomized Phase II Study Of The JAK2-Selective Inhibitor Fedratinib (SAR302503) In Patients With Myelofibrosis (MF)

Blood ◽  
2013 ◽  
Vol 122 (21) ◽  
pp. 4047-4047 ◽  
Author(s):  
Animesh Pardanani ◽  
Ayalew Tefferi ◽  
Catriona HM Jamieson ◽  
Nashat Y Gabrail ◽  
Claudia Lebedinsky ◽  
...  
Keyword(s):  
High Risk ◽  
Disease Progression ◽  
Phase Ii ◽  
Research Funding ◽  
Phase Ii Study ◽  
Hematologic Toxicity ◽  
Costal Margin ◽  
Spleen Volume ◽  
Randomized Phase Ii ◽  
Grade 3

Abstract Background We previously reported that patients with MF enrolled in a randomized Phase II study of fedratinib (SAR302503) (ARD11936; NCT01420770) had clinically meaningful reductions in splenomegaly and improvements in MF-associated constitutional symptoms after 24 weeks of treatment (Haematologica 2013;98:S1113). Here, we report updated efficacy and safety results from this study after 48 weeks of treatment (end of Cycle 12). Methods Patients with intermediate risk-2 or high-risk MF were randomized to receive once-daily fedratinib at doses of 300 mg, 400 mg, or 500 mg, for consecutive 4-weekly cycles, until disease progression or unacceptable toxicity. Eligible patients were aged ≥18 years, with palpable splenomegaly (5 cm below costal margin), and a platelet count ≥50 × 109/L. The primary measure for this study was percent change in spleen volume from baseline at the end of Cycle 3 (Blood 2012:120;Abstract 2837. Haematologica 2013;98:S1113). Endpoints for the current analysis included spleen response (≥35% reduction in spleen volume from baseline, assessed by a blinded independent central review by MRI), safety, and changes in bone marrow fibrosis (BMF). Results A total of 31 patients were randomized and treated: median age 63 years, 52% male, 58% primary MF, 58% high-risk MF, 90% JAK2V617F positive. The median numbers of treatment cycles were 12, 14, and 13 in the 300 mg, 400 mg and 500 mg dose groups, respectively, with median durations of exposure of 48.2, 56.2, and 52.4 weeks. At the cut-off date for this analysis, 21 patients (68%) remained on treatment; the most common reasons for treatment discontinuation were adverse events (AEs) (n=5) and withdrawal of consent (n=2). Overall, 58% (18/31) of patients achieved a spleen response at any time during treatment. The median spleen response duration was >35 weeks at all doses (Table). At Week 48, a spleen response was achieved by 30% (3/10), 80% (8/10), and 45% (5/11) of patients in the 300 mg, 400 mg, and 500 mg groups, respectively. Responses were generally maintained across all treatment groups. From Week 24 to Week 48 two additional patients achieved a spleen response (both in the 400 mg group), while one patient in the 500 mg group did not maintain a response (this patient had a fedratinib dose reduction to 200 mg). Changes in BMF up to Week 48 are being evaluated. The most common non-hematologic AE was diarrhea, with a Grade 3 rate of 13% (4/31 patients) but no Grade 4 cases were recorded. The rates of diarrhea decreased after the first cycle of treatment; from Cycle 2, the incidence of diarrhea (any grade) did not exceed 16% (5/31) at any cycle, and only one case of diarrhea was reported at Week 48 (end of Cycle 12). Anemia was the most-common hematologic toxicity, with a Grade 3 rate of 58% (18/31); no Grade 4 cases were reported. All Grades thrombocytopenia occurred in 55% (17/31) of patients, Grade 3 in three patients, and Grade 4 in two patients. Discontinuation of treatment due to AEs occurred in five patients over the 48 weeks (300 mg [n=2]; 400 mg [n=2]; 500 mg [n=1]), with two cases reported after Week 24 (dyspnea and leukocytosis [400 mg]; anemia and thrombocytopenia [500 mg]). There were 2 deaths (one in the 300 mg group due to unknown reasons [85 days after fedratinib discontinuation] and one in the 500 mg group due to disease progression [36 days after fedratinib discontinuation]). No cases of leukemic transformation were reported. Conclusions This updated analysis of the ARD11936 Phase II trial shows that treatment with fedratinib results in durable reductions in splenomegaly in patients with MF. No additional safety signals were observed with prolonged exposure to fedratinib. This study was sponsored by Sanofi. Disclosures: Pardanani: Sanofi, Bristol Myers Squibb, PharmaMar and JW Pharma: Clinical trial support Other. Jamieson:J&J, Roche: Research Funding; Sanofi: Membership on an entity’s Board of Directors or advisory committees. Lebedinsky:Sanofi: Employment. Gao:Sanofi: Employment. Talpaz:Novartis, Bristol-Myers Squibb, Ariad, Deciphera: Research Funding; Novartis, Bristol-Myers Squibb, Ariad, Deciphera: Speakers Bureau.

Randomized phase II study of carboplatin and paclitaxel (CP) versus gemcitabine and vinorelbine (GV) in performance status (PS) 2 patients with advanced non-small cell lung cancer (NSCLC): Preliminary results of West Japan Thoracic Oncology Group 0004

2006 ◽  
Vol 24 (18_suppl) ◽  
pp. 7151-7151
Author(s):  
H. Kaneda ◽  
K. Nakagawa ◽  
H. Saito ◽  
T. Kashii ◽  
Y. Iwamoto ◽  
...  
Keyword(s):  
Phase Ii ◽  
Liver Dysfunction ◽  
Advanced Nsclc ◽  
Phase Ii Study ◽  
Performance Status ◽  
Stage Iiib ◽  
Toxicity Data ◽  
Pulmonary Infiltrates ◽  
Randomized Phase Ii ◽  
Platinum Based Chemotherapy

7151 Background: A platinum-based chemotherapy is a standard treatment in PS 0–1 patients with advanced NSCLC and a non-platinum doublet is an alternative option. However, the role of combination chemotherapy remains to be defined in PS 2 patients with advanced NSCLC. We have conducted a randomized phase II study to compare the efficacy and safety of CP versus GV in PS 2 patients with NSCLC. Methods: Chemotherapy-naive ECOG PS 2 patients with stage IIIB (malignant effusion) or IV NSCLC were enrolled in this study. Patients were randomized to carboplatin AUC 6 and paclitaxel 200 mg/m2 day 1 every 3 weeks or gemcitabine 1,000 mg/ m2 and vinorelbine 25mg/m2 day 1, 8 every 3 weeks. The primary endpoint was 1-year survival rate and secondary endpoint were response rate, toxicity, time to progression and quality of life. Results: A total of 89 patients were enrolled and 86 were eligible: 42 patients (median age 64 years, male/female 31/11, stage IIIB/IV 7/35) in CP and 44 patients (median age 67 years, male/female 33/11, stage IIIB/IV 7/37) in GV. Of 84 patients evaluable for response, one complete response and 11 partial responses were obtained in CP (29.3%) and 9 partial responses in GV (20.9%). As of 12/05, toxicity data were available in 80 patients. Grade 3/4 toxicity in CP and GV included neutropenia 65.8% vs 63.4%, anemia 13.2% vs 31.7%, thrombocytopenia 7.9% vs 12.2%, liver dysfunction 2.6% vs 9.8%, febrile neutropenia 15.4% vs 12.2%, infection 30.8% vs 22%, nausea/vomiting 15.4% vs 2.4%, constipation 23.1% vs 7.3% pulmonary infiltrates 5.1% vs 12.2% and neuropathy 5.1% vs 0%. Conclusions: CP and GV were feasible and effective in PS 2 patients with advanced NSCLC. GV caused more anemia, thrombocytopenia, liver dysfunction and pulmonary infiltrates, while CP produced more nausea/vomiting, constipation and neuropathy. Response and toxicity data in all pts in each arm will be presented at the meeting. No significant financial relationships to disclose.

Efficacy and toxicity of two schedules of R-CHOP plus bortezomib in front-line B lymphoma patients: A randomized phase II trial from the Groupe d’Etude des Lymphomes de l’Adulte (GELA)

2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 8010-8010 ◽  
Author(s):  
N. Mounier ◽  
V. Ribrag ◽  
C. Haioun ◽  
G. Salles ◽  
J. Golfier ◽  
...  
Keyword(s):  
Phase Ii ◽  
Performance Status ◽  
Hematologic Malignancies ◽  
Front Line ◽  
Cardiac Events ◽  
Serious Adverse Events ◽  
B Lymphoma ◽  
Randomized Phase Ii ◽  
Histological Transformation ◽  
Grade 3

8010 Background: Bortezomib is the first proteasome inhibitor that showed promising activity in hematologic malignancies. In Jan 2005, we initiated a phase II randomized trial to evaluate front-line R-CHOP + bortezomib in B lymphoma pts. Methods: 6 cycles of standard R-CHOP (d1=d21) were planned, pts were randomized between 2 schedules of bortezomib: arm A (d 1,4,8,11), arm B (d 1,8). For the first 24 pts (step1), bortezomib was administred at 1 mg/m2 in arm A and 1.3 mg/m2 in arm B. For the next 24 pts (step2), it was increased at 1.3 mg/m2 and 1.6 mg/m2 respectively. G-CSF and EPO supports were allowed. Primary endpoint was CR rate after 6 cycles. Results: The trial was closed in Apr 2006 after inclusion of 49 pts. Sex ratio M/F was 28 /21. Median age: 63 years [32–76]. Pathology: 4 Lymphoplasmocytic, 4 small lymphocyte, 8 MZL, 2 Malt, 11 FL , 7 FL with histological transformation, 4 Mantle cell and 9 DLBC without adverse factor. Performance status 2–4: 4 pts; stage 4: 33 pts; LDH>N: 16 pts and IPI 2–3: 18 pts. According to triangular-test interim analysis (Jan 2006), arm A was closed at 20 pts (11 step1, 9 step2). 29 pts received arm B (10 step1, 19 step2). 290 cycles of R- CHOP and 819 injections of bortezomid were given. In arm A, 5/20 pts received less than 90% of scheduled dose of bortezomib (all in step2); in arm B, 7/29 pts (2 step1 and 5 step2). Grade 3–4 thrombopenia occurred in 14% of cycles (35% arm A, 0% arm B, 14% step2), Grade 3–4 leucopenia in 41 % (35% arm A, 45% arm B, 43% step2). Neurological toxicity occurred in 21 pts: grade 2 in 11 (1 arm A, 10 arm B, 9 in step2) and grade 3–4 in 10 (5 arm A, 5 arm B, 9 in step 2). 6 of them were considered as serious adverse events. Other grade 3–4 toxicities were 1 constipation (1 arm B, step2), 3 infections (2 arm A, 1 arm B, 2 step 2) and 2 cardiac events (1 arm A, 1 arm B). 48 pts were evaluable for response: 40 achieved CR/CRU: 18/20 in arm A, 22/28 in arm B. There were 5 PR (1 arm A, 4 arm B), 1 SD (arm A) and 2 PD (arm B). 19/21 pts achieved CR in step 1 and 21/27 in step 2. After 1 year median follow up, OS was 100% and EFS 80%. Conclusions: R- CHOP+Bortezomid is an effective regimen with 83% CR rate. However, the higher doses of bortezomib lead to severe neuropathy and suggest that association with vinca alcaloides should be avoided. No significant financial relationships to disclose.

Phase II study of TS-1 (S) plus cisplatin (P) with concurrent thoracic radiotherapy for unresectable stage III non-small cell lung cancer (NSCLC)

2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 18070-18070
Author(s):  
F. Ohyanagi ◽  
N. Yamamoto ◽  
A. Horiike ◽  
T. Horai ◽  
K. Gomi ◽  
...  
Keyword(s):  
Phase Ii ◽  
Response Rate ◽  
Phase Ii Study ◽  
Performance Status ◽  
Progression Free Survival ◽  
Stage Iii ◽  
Fourth Generation ◽  
Unresectable Stage ◽  
Stage Iii Nsclc ◽  
Grade 3

18070 Background: Although combined chemoradiotherapy is the standard of care in stage III NSCLC, the optimal chemotherapy regimen is not established. S-1, a fourth-generation oral fluoropyrimidine is an active new agent for NSCLC and the combination with cisplatin has a favorable toxicity profile. The objective of this study was to evaluate feasibility and efficacy of S plus P with concurrent radiation for unresectable stage III NSCLC. Methods: Patients with histologically or cytologically confirmed NSCLC, 20 to 75 years in age, performance status 0–1, with no prior chemotherapy were eligible for the study. Patients were treated with P (60 mg/m2 on day 1) and S (orally at 40 mg/m2/dose bid (80 mg/m2/d), on days 1 to 14) repeated every 3–4 weeks for 4 cycles and TRT (60 Gy/30 fr over 6 weeks starting on day 2). The primary endpoint was the response rate (RR), and planned sample size for this phase II study was 28 patients (Simon’s two-stage minimax design, P0=70%, P1=90%, a =0.1, β = 0.1). Results: Of 28 patients enrolled between August 2005 and October 2006, 28 were evaluable. There were 24 males and 4 females, median age of 63 (range 40–74) and 11 IIIA and 17 IIIB. Chemoradiotherapy was well tolerated; 2 cycles of SP and 60 Gy of TRT were administered in all patients and 24 (86%) patients received 4 cycles of SP. During concurrent chemoradiotherapy, grade 3 toxicities were neutropenia (8 pts), leukopenia (6 pts), fatigue (6 pts), anorexia (5 pts), febrile neutropenia (4 pts) and, esophagitis (4 pts). Only one grade 4 leukopenia were observed. During consolidation therapy, grade 3–4 neutropenia, anemia, esophagitis, and pneumonitis were developed in 4, 1, 1 and 2 patients, respectively. No toxic deaths have occurred. Overall RR was 85.7% (95% CI: 79.1- 98.7%) with 4 SDs and 24 PRs. The median progression-free survival and median survival is not mature enough to estimate as only 4 progression and no deaths have occurred. Conclusions: This chemoradiotherapy regimen produced promising response rate in patients with stage III NSCLC and it seems to be well-tolerated. No significant financial relationships to disclose.

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