Preliminary results of a randomized phase III trial comparing streptozotocin plus fluorouracil versus interferon for metastatic carcinoid tumors (FNCLCC - FFCD 9710)

2006 ◽  
Vol 24 (18_suppl) ◽  
pp. 4090-4090
Author(s):  
J. F. Seitz ◽  
L. Dahan ◽  
P. Rougier ◽  
J. L. Raoul ◽  
E. Gamelin ◽  
...  
Keyword(s):  
Interferon Alpha ◽  
Survival Rates ◽  
Progression Free Survival ◽  
Median Number ◽  
Carcinoid Tumors ◽  
Phase Iii ◽  
Expected Improvement ◽  
Metastatic Carcinoid ◽  
Female Ratio ◽  
Phase Iii Trial

4090 Background: Streptozotocin and 5 FU in combination is widely used for the treatment of advanced carcinoids tumors. Interferon is an effective treatment of the malignant carcinoids tumors. This randomized multicenter phase III trial compared those treatments in patients with metastatic carcinoïd tumors. Methods: Patients with metastatic carcinoid tumors, clinical or biological progression, WHO status 0–2 (PS) and age ≤ 75 years were randomized 1:1 between interferon alpha 2a recombinant (3MU × 3 per weeks) and 5FU (400 mg/m2/day day1 to day5) plus streptozotocin (500 mg/m2/day day1 to day5) every 6 weeks. Stratification was done according to center, PS and anterior treatment. Primary endpoint was progression free-survival (PFS). It was required to include 120 pts and to observe 38 progressions to detect an expected improvement in 1year PFS from 55% to 80% (bilateral α = 5 % and β = 20 %). Secondary endpoints included 1-year and 2-year overall survival (OS). Intent to treat analyses were performed. Results: From February 1998 to june 2004, in 23 centers, 63 patients has been included, 32 in 5FU-STZ arm and 32 in interferon arm: median age (59 years [37–77] vs 63 [39–75]), male/female ratio (1.2 vs 1), PS 0–1 (91% vs 97%), anterior chemotherapy (13% vs 16%), surgery (69% vs 59%), radiotherapy (6% vs 0%) are well balanced between arms. The median number of 5FU-STZ and Interferon cycles was respectively 5 and 4. After a median follow-up of 26 months, the median OS for interferon was 44.3 months versus 37.7 months for chemotherapy: HR = 0.90 [0.43–1.90]; 1- year and 2-year survival rates were 89% and 72% for interferon versus 84% and 73% for chemotherapy. Conclusions: Interferon alpha 2a does not prolong OS in advanced metastatic carcinoid tumors as compared to the combination of 5FU-streptozotocin. After checking clinical and biological progression, PFS analyses will be presented at the meeting. No significant financial relationships to disclose.

scholarly journals Phase III trial of chemotherapy using 5-fluorouracil and streptozotocin compared with interferon α for advanced carcinoid tumors: FNCLCC–FFCD 9710

2009 ◽  
Vol 16 (4) ◽  
pp. 1351-1361 ◽  
Author(s):  
Laetitia Dahan ◽  
Frank Bonnetain ◽  
Philippe Rougier ◽  
Jean-Luc Raoul ◽  
Eric Gamelin ◽  
...  
Keyword(s):  
Overall Survival ◽  
Sex Ratio ◽  
Progression Free Survival ◽  
Carcinoid Tumors ◽  
Phase Iii ◽  
Interferon Α ◽  
Metastatic Carcinoid ◽  
Phase Iii Trial ◽  
Free Survival ◽  
Multicenter Phase

The aim of this randomized multicenter phase III trial was to compare chemotherapy and interferon (IFN) in patients with metastatic carcinoid tumors. Patients with documented progressive, unresectable, metastatic carcinoid tumors were randomized between 5-fluorouracil plus streptozotocin (day 1–5) and recombinant IFN-α-2a (3 MU×3 per week). Primary endpoint was progression-free survival (PFS). From February 1998 to June 2004, 64 patients were included. The two arms were well matched for median age, sex ratio, PS 0–1, previous chemotherapy, surgery, or radiotherapy. The median PFS for chemotherapy was 5.5 months versus 14.1 for IFN (hazard ratio=0.75 (0.41–1.36)). Overall survival (OS), tolerance, and effects on carcinoid symptoms were not significantly different. Despite a trend in favor of IFN, there was no difference in PFS and OS in advanced metastatic carcinoid tumors and therapeutic effect of both treatments was mild.

Topotecan plus carboplatin versus standard therapy with paclitaxel plus carboplatin (PC) or gemcitabin plus carboplatin (GC) or carboplatin plus pegylated doxorubicin (PLDC): A randomized phase III trial of the NOGGO-AGO-Germany-AGO Austria and GEICO-GCIG intergroup study (HECTOR).

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. 5031-5031 ◽  
Author(s):  
Jalid Sehouli ◽  
Werner Meier ◽  
Pauline Wimberger ◽  
Radoslav Chekerov ◽  
Antje Belau ◽  
...  
Keyword(s):  
Standard Therapy ◽  
Progression Free Survival ◽  
Median Number ◽  
Phase Iii ◽  
Phase Iii Trial ◽  
Platinum Sensitive ◽  
Best Response ◽  
Phase Iii Study ◽  
Number Of Cycles

5031 Background: We present the efficacy data from a phase III study of topotecan (T) plus carboplatin (C) versus standard therapy with paclitaxel plus carboplatin (PC) or gemcitabine plus carboplatin (GC) or carboplatin plus pegylated doxorubicin (PLDC). Methods: From 02/07 to 12/09, 590 pts were screened and 550 pts were randomized to either T (0.75mg/m²/d1-3/q21d) + C (AUC 5/d1/q21d) or to standard therapy with CP or GC or PLDC based on patient preference. Progression free survival at 1 year was defined as primary endpoint. Results: Median number of cycles was 6 (range 0-9) in both arms. Most patients preferred GC (78%) in the standard therapy arm.. Best Response (CR+PR) was 73.1% (95%CI) and 75.1% (95%CI) for the CA. Median follow-up was 18 (0-52) months for TC and 20 (0-48) months for standard therapy. TC failed to show any advantage regarding 1-yr.-PFS or OAS. Conclusions: The combination of topotecan plus carboplatin failed to improve PFS or OAS in platinum sensitive relapsed ovarian cancer. In addition, carboplatin plus gemcitabine was well tolerated with lower rates of severe and long-lasting (neuropathy) toxicities compared to paclitaxel-carboplatin. [Table: see text]

IFCT-GFPC-0701 MAPS trial, a multicenter randomized phase III trial of pemetrexed-cisplatin with or without bevacizumab in patients with malignant pleural mesothelioma (MPM).

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. TPS7112-TPS7112 ◽  
Author(s):  
Gerard Zalcman ◽  
Julien Mazieres ◽  
Arnaud Scherpereel ◽  
Jacques Margery ◽  
Denis Moro-Sibilot ◽  
...  
Keyword(s):  
Survival Rates ◽  
Progression Free Survival ◽  
Phase Iii ◽  
Absolute Difference ◽  
Phase Iii Trial ◽  
Rassf1a Methylation ◽  
Micro Rnas ◽  
Modified Recist ◽  
Tissue Specimens ◽  
A Prospective Study

TPS7112 Background: MPM median OS does not exceed 13 months with pem/CDDP doublet. U.S. Intergroup phase II trial of gemcitabine/CDDP, with or without bevacizumab, gave an appealing 15.6 months median OS in the bevacizumab arm. French Intergroup aimed to test pem/CDDP with bevacizumab (PCB), in a randomized phase III trial. Methods: Eligible patients had unresectable histologically proved MPM, no prior chemo, PS 0-2, no thrombosis, nor bleeding. Primary endpoint: The primary outcome will be survival. The secondary endpoint will be Progression-Free Survival. Patients received pem 500 mg/m2, CDDP 75 mg/m2 (PC),at D1, and vitamin B12 +B9 substitution, with (arm B) or without bevacizumab (arm A), 15 mg/kg Q21D, for 6 cycles. Arm B nonprogressive patients received bevacizumab maintenance therapy until progression or toxicity. 445 patients to be recruited during a period 48 months, with at least 24 months of follow-up, and 385 events (deaths), will be needed to assure a power of 80% and detect at least a 4.3 months of median survival increase. This hypothesis leads to a Hazard Ratio (HR) of 1.33 and a 3-years survival of 14.7% in control arm and 23.6 % in experimental arm, with an absolute difference of 8.9% in survival rates. Accrual status: The first patient was included in February 2008. On January 31, 2012, 257 patients from 85 French centers had been enrolled. The end of accrual can be expected for September 2013. Ancillary studies: For molecular biomarker analyses, thoracoscopic tissue specimens (TS, ERCC1, MSH2, TUBB3, NF2, p16, RASSF1A methylation,15 microRNAs ) and blood samples (micro-RNAS, VEGF, osteopontin, SRMP) at diagnosis are centrally collected. Finally, a prospective study comparing PET-CT to standard CT with central blinded analysis, is currently on-going for evaluation of response, and accuracy of modified RECIST criteria for mesothelioma.

scholarly journals Durvalumab in NSCLC: latest evidence and clinical potential

2018 ◽  
Vol 10 ◽  
pp. 175883591880415 ◽  
Author(s):  
Nerea Muñoz-Unceta ◽  
Isabel Burgueño ◽  
Elizabeth Jiménez ◽  
Luis Paz-Ares
Keyword(s):  
Cytotoxic T Lymphocyte ◽  
Checkpoint Inhibitors ◽  
Survival Rates ◽  
Progression Free Survival ◽  
Phase Iii ◽  
Significant Activity ◽  
Unresectable Stage ◽  
Favourable Safety ◽  
Favourable Safety Profile ◽  
Nsclc Patients

Advances in immunotherapy have led to radical improvements in outcomes, including overall survival, such as in non-small cell lung cancer (NSCLC) patients with metastatic disease treated with immune checkpoint inhibitors. More recently, promising results have been obtained in earlier disease settings, and combinations with other therapies are being actively investigated. Durvalumab, a monoclonal antibody directed against the programmed death ligand 1, has demonstrated significant activity in NSCLC, including increased progression-free survival rates after chemoradiation for unresectable stage III disease, with a favourable safety profile. Clinical trials, including phase III studies, are ongoing as monotherapy and in combination with chemotherapy, radiotherapy and other immunotherapies, such as the anti-cytotoxic T-lymphocyte antigen 4 drug tremelimumab, in diverse stages of the disease.

Phase III Trial Comparing Oral S-1 Plus Carboplatin With Paclitaxel Plus Carboplatin in Chemotherapy-Naïve Patients With Advanced Non–Small-Cell Lung Cancer: Results of a West Japan Oncology Group Study

2010 ◽  
Vol 28 (36) ◽  
pp. 5240-5246 ◽  
Author(s):  
Isamu Okamoto ◽  
Hiroshige Yoshioka ◽  
Satoshi Morita ◽  
Masahiko Ando ◽  
Koji Takeda ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Survival Rates ◽  
Area Under The Curve ◽  
Small Cell ◽  
Phase Iii ◽  
Small Cell Lung ◽  
Open Label ◽  
Phase Iii Trial

Purpose The primary goal of this open-label, multicenter, randomized phase III trial was to determine whether treatment with carboplatin plus the oral fluoropyrimidine derivative S-1 was noninferior versus that with carboplatin plus paclitaxel with regard to overall survival (OS) in chemotherapy-naive patients with advanced non–small-cell lung cancer (NSCLC). Patients and Methods A total of 564 patients were randomly assigned to receive either carboplatin (area under the curve, 5) on day 1 plus oral S-1 (40 mg/m2 twice per day) on days 1 to 14 or carboplatin (area under the curve, 6) plus paclitaxel (200 mg/m2) on day 1 every 21 days. Results At the planned interim analysis, with a total of 268 death events available, the study passed the O'Brien-Fleming boundary of 0.0080 for a positive result and noninferiority of carboplatin and S-1 compared with carboplatin and paclitaxel was confirmed for OS (hazard ratio, 0.928; 99.2% CI, 0.671 to 1.283). Median OS was 15.2 months in the carboplatin and S-1 arm and 13.3 months in the carboplatin and paclitaxel arm, with 1-year survival rates of 57.3% and 55.5%, respectively. Rates of leukopenia or neutropenia of grade 3/4, febrile neutropenia, alopecia, and neuropathy were more frequent in the carboplatin and paclitaxel arm, whereas thrombocytopenia, nausea, vomiting, and diarrhea were more common in the carboplatin and S-1 arm. The carboplatin and S-1 arm had significantly more dose delays than the carboplatin and paclitaxel arm. Conclusion Oral S-1 with carboplatin was noninferior in terms of OS compared with carboplatin and paclitaxel in patients with advanced NSCLC, and is thus a valid treatment option.

scholarly journals Reduced-Dose Radiation Therapy for HPV-Associated Oropharyngeal Carcinoma (NRG Oncology HN002)

2021 ◽  
pp. JCO.20.03128
Author(s):  
Sue S. Yom ◽  
Pedro Torres-Saavedra ◽  
Jimmy J. Caudell ◽  
John N. Waldron ◽  
Maura L. Gillison ◽  
...  
Keyword(s):  
Radiation Therapy ◽  
Radiation Treatment ◽  
Survival Rates ◽  
Progression Free Survival ◽  
Phase Iii ◽  
Oropharyngeal Carcinoma ◽  
Reduced Dose ◽  
Phase Iii Study ◽  
Grade 3 ◽  
Dose Radiation

PURPOSE Reducing radiation treatment dose could improve the quality of life (QOL) of patients with good-risk human papillomavirus–associated oropharyngeal squamous cell carcinoma (OPSCC). Whether reduced-dose radiation produces disease control and QOL equivalent to standard chemoradiation is not proven. PATIENTS AND METHODS In this randomized, phase II trial, patients with p16-positive, T1-T2 N1-N2b M0, or T3 N0-N2b M0 OPSCC (7th edition staging) with ≤ 10 pack-years of smoking received 60 Gy of intensity-modulated radiation therapy (IMRT) over 6 weeks with concurrent weekly cisplatin (C) or 60 Gy IMRT over 5 weeks. To be considered for a phase III study, an arm had to achieve a 2-year progression-free survival (PFS) rate superior to a historical control rate of 85% and a 1-year mean composite score ≥ 60 on the MD Anderson Dysphagia Inventory (MDADI). RESULTS Three hundred six patients were randomly assigned and eligible. Two-year PFS for IMRT + C was 90.5% rejecting the null hypothesis of 2-year PFS ≤ 85% ( P = .04). For IMRT, 2-year PFS was 87.6% ( P = .23). One-year MDADI mean scores were 85.30 and 81.76 for IMRT + C and IMRT, respectively. Two-year overall survival rates were 96.7% for IMRT + C and 97.3% for IMRT. Acute adverse events (AEs) were defined as those occurring within 180 days from the end of treatment. There were more grade 3-4 acute AEs for IMRT + C (79.6% v 52.4%; P < .001). Rates of grade 3-4 late AEs were 21.3% and 18.1% ( P = .56). CONCLUSION The IMRT + C arm met both prespecified end points justifying advancement to a phase III study. Higher rates of grade ≥ 3 acute AEs were reported in the IMRT + C arm.

Phase III Trial Comparing Radical Radiotherapy With and Without Cisplatin Chemotherapy in Patients With Advanced Squamous Cell Cancer of the Cervix

2002 ◽  
Vol 20 (4) ◽  
pp. 966-972 ◽  
Author(s):  
R. Pearcey ◽  
M. Brundage ◽  
P. Drouin ◽  
J. Jeffrey ◽  
D. Johnston ◽  
...  
Keyword(s):  
Squamous Cell ◽  
Squamous Cell Cancer ◽  
Cell Cancer ◽  
Survival Rates ◽  
Progression Free Survival ◽  
Lymph Node Involvement ◽  
Phase Iii ◽  
Gynecology And Obstetrics ◽  
Significant Difference ◽  
Cancer Of The Cervix

PURPOSE: To test the hypothesis that cisplatin (CDDP) administered concurrently with standard radiotherapy (RT) would improve pelvic control and survival in patients with advanced squamous cell cancer of the cervix. PATIENTS AND METHODS: A total of 259 patients with International Federation of Gynecology and Obstetrics stage IB to IVA squamous cell cervical cancer with central disease ≥ 5 cm or histologically confirmed pelvic lymph node involvement were randomized to receive RT (external-beam RT plus brachytherapy) plus weekly CDDP chemotherapy (40 mg/m2) (arm 1) or the same RT without chemotherapy (arm 2). RESULTS: A total of 253 patients were available for analysis. Median follow-up was 82 months. No significant difference was found in progression-free survival (P = .33). No significant difference in 3- and 5-year survival rates was found (69% v 66% and 62% v 58%, respectively; P = .42). The hazard ratio for survival (arm 2 to arm 1) was 1.10 (95% confidence interval, 0.75 to 1.62). CONCLUSION: This study did not show a benefit to either pelvic control or survival by adding concurrent weekly CDDP chemotherapy in a dose of 40 mg/m2 to radical RT as given in this trial. Careful attention to RT details is important for achieving optimum outcome for patients with this disease.

scholarly journals CheckMate-032 Study: Efficacy and Safety of Nivolumab and Nivolumab Plus Ipilimumab in Patients With Metastatic Esophagogastric Cancer

2018 ◽  
Vol 36 (28) ◽  
pp. 2836-2844 ◽  
Author(s):  
Yelena Y. Janjigian ◽  
Johanna Bendell ◽  
Emiliano Calvo ◽  
Joseph W. Kim ◽  
Paolo A. Ascierto ◽  
...  
Keyword(s):  
Gastroesophageal Junction ◽  
Objective Response ◽  
Locally Advanced ◽  
Survival Rates ◽  
Progression Free Survival ◽  
The United States ◽  
Phase Iii ◽  
Programmed Death Ligand 1 ◽  
Programmed Death ◽  
Esophagogastric Cancer

Purpose Metastatic esophagogastric cancer treatments after failure of second-line chemotherapy are limited. Nivolumab demonstrated superior overall survival (OS) versus placebo in Asian patients with advanced gastric or gastroesophageal junction cancers. We assessed the safety and efficacy of nivolumab and nivolumab plus ipilimumab in Western patients with chemotherapy-refractory esophagogastric cancers. Patients and Methods Patients with locally advanced or metastatic chemotherapy–refractory gastric, esophageal, or gastroesophageal junction cancer from centers in the United States and Europe received nivolumab or nivolumab plus ipilimumab. The primary end point was objective response rate. The association of tumor programmed death-ligand 1 status with response and survival was also evaluated. Results Of 160 treated patients (59 with nivolumab 3 mg/kg, 49 with nivolumab 1 mg/kg plus ipilimumab 3 mg/kg, 52 with nivolumab 3 mg/kg plus ipilimumab 1 mg/kg), 79% had received two or more prior therapies. At the data cutoff, investigator-assessed objective response rates were 12% (95% CI, 5% to 23%), 24% (95% CI, 13% to 39%), and 8% (95% CI, 2% to 19%) in the three groups, respectively. Responses were observed regardless of tumor programmed death-ligand 1 status. With a median follow-up of 28, 24, and 22 months across the three groups, 12-month progression-free survival rates were 8%, 17%, and 10%, respectively; 12-month OS rates were 39%, 35%, and 24%, respectively. Treatment-related grade 3/4 adverse events were reported in 17%, 47%, and 27% of patients in the three groups, respectively. Conclusion Nivolumab and nivolumab plus ipilimumab demonstrated clinically meaningful antitumor activity, durable responses, encouraging long-term OS, and a manageable safety profile in patients with chemotherapy-refractory esophagogastric cancer. Phase III studies evaluating nivolumab or nivolumab plus ipilimumab in earlier lines of therapy for esophagogastric cancers are underway.

Phase III Trial of Infusional Fluorouracil, Leucovorin, Oxaliplatin, and Irinotecan (FOLFOXIRI) Compared With Infusional Fluorouracil, Leucovorin, and Irinotecan (FOLFIRI) As First-Line Treatment for Metastatic Colorectal Cancer: The Gruppo Oncologico Nord Ovest

2007 ◽  
Vol 25 (13) ◽  
pp. 1670-1676 ◽  
Author(s):  
Alfredo Falcone ◽  
Sergio Ricci ◽  
Isa Brunetti ◽  
Elisabetta Pfanner ◽  
Giacomo Allegrini ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Metastatic Colorectal Cancer ◽  
Progression Free Survival ◽  
Phase Iii ◽  
Peripheral Neurotoxicity ◽  
Phase Iii Trial ◽  
Free Survival ◽  
Secondary Resection ◽  
Phase Iii Study ◽  
Grade 3

Purpose The Gruppo Oncologico Nord Ovest (GONO) conducted a phase III study comparing fluorouracil, leucovorin, oxaliplatin, and irinotecan (FOLFOXIRI [irinotecan 165 mg/m2 day 1, oxaliplatin 85 mg/m2 day 1, leucovorin 200 mg/m2 day 1, fluorouracil 3,200 mg/m2 48-hour continuous infusion starting on day 1, every 2 weeks]) with infusional fluorouracil, leucovorin, and irinotecan (FOLFIRI). Methods Selection criteria included unresectable metastatic colorectal cancer, age 18 to 75 years, and no prior chemotherapy for advanced disease. The primary end point was response rate (RR). Results A total of 244 patients were randomly assigned. An increase of grade 2 to 3 peripheral neurotoxicity (0% v 19%; P < .001), and grade 3 to 4 neutropenia (28% v 50%; P < .001) were observed in the FOLFOXIRI arm. The incidence of febrile neutropenia (3% v 5%) and grade 3 to 4 diarrhea (12% v 20%) were not significantly different. Responses, as assessed by investigators, were, for FOLFIRI and FOLFOXIRI, respectively, complete, 6% and 8%; and partial, 35% and 58%, (RR, 41% v 66%; P = .0002). RR confirmed by an external panel was 34% versus 60% (P < .0001). The R0 secondary resection rate of metastases was greater in the FOLFOXIRI arm (6% v 15%; P = .033, among all 244 patients; and 12% v 36%; P = .017 among patients with liver metastases only). Progression-free survival (PFS) and overall survival (OS) were both significantly improved in the FOLFOXIRI arm (median PFS, 6.9 v 9.8 months; hazard ratio [HR], 0.63; P = .0006; median OS, 16.7 v 22.6 months; HR, 0.70; P = .032). Conclusion The FOLFOXIRI regimen improves RR, PFS, and OS compared with FOLFIRI, with an increased, but manageable, toxicity in patients with metastatic colorectal cancer with favorable prognostic characteristics. Further studies of FOLFOXIRI in combination with targeted agents and in the neoadjuvant setting are warranted.

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