Phase III study comparing cisplatin/vinorelbine plus cetuximab versus cisplatin/vinorelbine as first-line treatment for patients with epidermal growth factor (EGFR)-expressing advanced non-small cell lung cancer (NSCLC) (FLEX)

2006 ◽  
Vol 24 (18_suppl) ◽  
pp. 7109-7109 ◽  
Author(s):  
J. Von Pawel ◽  
K. Park ◽  
J. R. Pereira ◽  
A. Szczesna ◽  
C. Yu ◽  
...  
Keyword(s):  
Survival Time ◽  
Median Survival ◽  
Advanced Nsclc ◽  
Safety Information ◽  
Stage Iv ◽  
Progression Free Survival ◽  
Response Rates ◽  
Phase Iii ◽  
Survival Times ◽  
First Line

7109 Background: Cisplatin plus vinorelbine is a commonly used regimen for first-line therapy of advanced NSCLC, achieving response rates of 20–30% and median survival times of 6 to 11 months (mths). An earlier phase II trial investigated cetuximab in combination with cisplatin and vinorelbine in this setting and found improved response rates in the cetuximab arm, warranting this larger phase III trial. Methods: Patients (pts) with EGFR-expressing advanced NSCLC (stage IIIB with documented malignant pleural effusion and stage IV) were randomized 1:1 either to Group A (cetuximab 400 mg/m2 initial dose then 250 mg/m2 weekly, cisplatin 80 mg/m2 on day 1, vinorelbine 30 mg/m2 on day 1 and 8) or to Group B (cisplatin and vinorelbine as before) for a maximum of 6 three-weekly cycles. Cetuximab was administered until progression or unacceptable toxicity. Primary endpoint is overall survival time; secondary endpoints are progression-free-survival, tumor response, disease control, safety, and quality of life. Enrollment of 1,100 pts was planned to show an increase of median survival time of 25% with 90% power. The Data Safety Monitoring Board (DSMB) performed an independent preplanned safety analysis from the first 370 pts. Patients were followed for a minimum of 6 weeks (2 cycles). Results: Since November 2004, 1,037 pts have been randomized, 689 are under treatment, and 348 pts have discontinued the study. Demographics of the first 370 pts reflected known advanced NSCLC characteristics: 91% stage IV, median age 60 yrs (31–79), 38% female, 80% ECOG PS 0/1, 52% adenocarcinoma, 30% squamous cell carcinoma; 29% never-smokers, 17% Asian. The ten most frequent adverse events were: nausea, neutropenia, vomiting, anorexia, fatigue, constipation, anemia, febrile neutropenia, rash, and diarrhoea. Conclusions: The trial continued after review of all relevant baseline and safety information from the first 370 pts. Recruitment is ongoing. [Table: see text]

Weekly nab-paclitaxel in combination with carboplatin as first-line therapy in elderly patients (pts) with advanced non-small cell lung cancer (NSCLC).

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. 7590-7590
Author(s):  
Mark A. Socinski ◽  
Corey J. Langer ◽  
Isamu Okamoto ◽  
Jeremy K. Hon ◽  
Vera Hirsh ◽  
...  
Keyword(s):  
Advanced Nsclc ◽  
Stage Iv ◽  
Progression Free Survival ◽  
Phase Iii ◽  
First Line ◽  
Entire Study ◽  
First Line Therapy ◽  
Line Therapy ◽  
Patient Reported ◽  
Study Population

7590 Background: The median age of advanced NSCLC pts in the US is 71 years; yetelderly pts (≥70 years) are generally undertreated, with only ≈30% receiving systemic therapy. Hence, better, more tolerable therapeutic options are needed for this cohort. In a phase III trial nab-paclitaxel (nab-P, 130 nm albumin-bound paclitaxel particles) + carboplatin (C) vs solvent-based paclitaxel (sb-P) + C, significantly improved ORR, the primary endpoint (25% vs 33%, P = 0.005), with a 1-month improvement in OS (P = NS) and improved safety. This analysis evaluated efficacy and safety in pts ≥70 and <70 years old. Methods: Pts with untreated stage IIIB/IV NSCLC and with an ECOG score of 0/1 were randomized 1:1 (stratified by age [≥70 vs <70 years], region, stage, gender, and histology) to C AUC 6 day 1 and either nab-P 100 mg/m2 on days 1, 8, 15 or sb-P 200 mg/m2 day 1 q 21 days. ORR and progression-free survival (PFS) were determined by blinded centralized review. Results: Of the phase III study population, 15% were elderly (156/1052; 74 pts in the nab-P/C and 82 in the sb-P/C arms). Most elderly pts were male (72%), Caucasian (71%), and had stage IV disease (64%). In pts both ≥70 and <70 years old, ORR was higher in the nab-P/C vs sb-P/C arm (≥70: 34% vs 24%, P = 0.196; <70: 32% vs 25%, P = 0.013). In pts ≥70 years old, PFS trended in favor of nab-P/C (median 8.0 vs 6.8 months, HR: 0.687, P = 0.134); OS was significantly improved (median 19.9 vs 10.4 months, HR: 0.583, P = 0.009). In contrast, PFS (6.0 vs 5.8 median months, HR: 0.903, P = 0.256) and OS (11.4 vs 11.3 median months, HR: 0.999, P = 0.988) were similar for both treatment arms in pts <70 years old. Adverse events were similar in pts ≥70 years old vs the entire study population, with less grade 3/4 neutropenia (P < 0.05) and neuropathy (P < 0.05) and increased thrombocytopenia (P = NS) and anemia (P < 0.05) in the nab-P/C vs sb-P/C arms. In pts ≥70 years old, patient-reported FACT-taxane subscales revealed significantly less neuropathy, pain, and hearing loss in the nab-P/C vs sb-P/C arms (P < 0.001). Conclusions: In elderly pts with advanced NSCLC, nab-P/C as first-line therapy was well tolerated and led to improved ORR and PFS, with significantly longer OS vs sb-PC.

Effects of adding necitumumab to first-line chemotherapy in patients with stage IV non-small-cell lung cancer: Meta-analysis

2019 ◽  
Vol 26 (6) ◽  
pp. 1331-1342
Author(s):  
Irena Ilic ◽  
Sandra Sipetic ◽  
Jovan Grujicic ◽  
Milena Ilic
Keyword(s):  
Overall Survival ◽  
Objective Response Rate ◽  
Advanced Nsclc ◽  
Response Rate ◽  
Meta Analysis ◽  
Objective Response ◽  
Stage Iv ◽  
Progression Free Survival ◽  
First Line ◽  
Free Survival

Introduction Almost half of patients with non-small-cell lung cancer (NSCLC) are diagnosed at an advanced stage. Our aim was to assess the effects of adding necitumumab to chemotherapy in patients with stage IV NSCLC. Material and methods A comprehensive literature search was performed according to pre-specified inclusion and exclusion criteria. Data on overall survival, progression-free survival, objective response rate and adverse events were extracted. A meta-analysis was performed to obtain pooled hazard ratios (HR) and corresponding 95% confidence intervals (CI) for time-to-event data and pooled odds ratio (OR) with 95% CI for dichotomous outcomes. Results The meta-analysis included four randomized clinical trials with 2074 patients. The pooled results showed significant improvement for overall survival (HR = 0.87 (95% CI 0.79–0.95), p = 0.004) when necitumumab was added to chemotherapy in patients with advanced NSCLC. No statistically significant improvement was noted for progression-free survival and objective response rate (HR = 0.83 (95% CI 0.69–1.01), p = 0.06 and OR = 1.46 (95% CI 0.90–2.38), p = 0.13, respectively). Subgroup analysis showed that in patients with non-squamous NSCLC, there was no benefit in overall survival and objective response rate. Patients with advanced NSCLC who received necitumumab were at the highest odds of developing a skin rash (OR = 14.50 (95% CI 3.16–66.43), p = 0.0006) and hypomagnesaemia (OR = 2.77 (95% CI 2.23–3.45), p < 0.00001), while the OR for any grade ≥3 adverse event was 1.55 (95% CI 1.28–1.87, p < 0.00001). Conclusions The addition of necitumumab to standard chemotherapy in a first-line setting in patients with stage IV NSCLC results in a statistically significant improvement in overall survival, while the results were not significant for progression-free survival and objective response rate.

scholarly journals Cisplatin-Based First-Line Treatment of Elderly Patients With Advanced Non–Small-Cell Lung Cancer: Joint Analysis of MILES-3 and MILES-4 Phase III Trials

2018 ◽  
Vol 36 (25) ◽  
pp. 2585-2592 ◽  
Author(s):  
Cesare Gridelli ◽  
Alessandro Morabito ◽  
Luigi Cavanna ◽  
Andrea Luciani ◽  
Paolo Maione ◽  
...  
Keyword(s):  
Elderly Patients ◽  
Advanced Nsclc ◽  
Performance Status ◽  
Progression Free Survival ◽  
Phase Iii ◽  
First Line ◽  
Free Survival ◽  
Phase Iii Trials ◽  
Health Status Score

Purpose To test the efficacy of adding cisplatin to first-line treatment for elderly patients with advanced non–small-cell lung cancer (NSCLC) within a combined analysis of two parallel phase III trials, MILES-3 and MILES-4. Patients and Methods Patients with advanced NSCLC who were older than age 70 years with Eastern Cooperative Oncology Group performance status 0 to 1 were randomly assigned to gemcitabine or pemetrexed, without or with cisplatin. In each trial, 382 events were required to detect a hazard ratio (HR) of death of 0.75, with 80% power and two-tailed α of .05. Trials were closed prematurely because of slow accrual, but the joint database allowed us to analyze the efficacy of cisplatin on the basis of intention-to-treat and adjusted by trial, histotype, non-platinum companion drug, stage, performance status, sex, age, and size of the study center. Results From March 2011 to August 2016, 531 patients (MILES-3, 299; MILES-4, 232) were assigned to gemcitabine or pemetrexed without (n = 268) or with cisplatin (n = 263). Median age was 75 years, 79% were male, and 70% had nonsquamous histology. At a median 2-year follow-up, 384 deaths and 448 progression-free survival events were recorded. Overall survival was not significantly prolonged with cisplatin (HR, 0.86; 95% CI, 0.70 to 1.05; P = .14) and global health status score of quality of life was not improved, whereas progression-free survival (HR, 0.76; 95% CI, 0.63 to 0.92; P = .005) and objective response rate (15.5% v 8.5%; P = .02) were significantly better. Significantly more severe hematologic toxicity, fatigue, and anorexia were found with cisplatin. Conclusion The addition of cisplatin to single-agent chemotherapy does not significantly prolong overall survival, and it does not improve global health status score of quality of life in elderly patients with advanced NSCLC.

A phase II study of picoplatin (pico) as second-line therapy for patients (pts) with small cell lung cancer (SCLC) who have resistant or refractory disease or have relapsed within 180 days of completing first-line, platinum (plat)-containing chemotherapy

2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 7722-7722 ◽  
Author(s):  
D. Bentzion ◽  
O. Lipatov ◽  
I. Polyakov ◽  
R. MacKintosh ◽  
J. Eckardt ◽  
...  
Keyword(s):  
Median Survival ◽  
Stable Disease ◽  
Single Agent ◽  
Progression Free Survival ◽  
Phase Iii ◽  
Refractory Disease ◽  
Phase 2 ◽  
First Line ◽  
Line Therapy ◽  
Grade 3

7722 Background: Pico is a sterically hindered plat analogue designed to overcome plat resistance with improved safety and efficacy. In >600 pts pico had single-agent activity in lung, prostate, ovarian and other malignancies with rare significant nephro-, oto-, or neurotoxicity (∼2% grade 3 and 0% grade 4). In a previous phase 2 study of single agent pico as 2nd line therapy in SCLC, 4 of 48 pts (8%) had a partial response and 21 (44%) stable disease. Median survival was 27.0 (95% CI = 16–35) wks. This multi-center phase 2 trial was designed to confirm the activity of pico as 2nd line monotherapy for plat-resistant SCLC. Methods: Pts with SCLC who either 1) failed or progressed through 1st line plat-containing chemo (refractory disease), or 2) initially responded to 1st line plat-containing chemo and then relapsed/ progressed within 3 months (resistant disease), or 3) initially responded and then relapsed/progressed between 90 to 180 days (sensitive, relapsed 90 to 180 days), had measurable disease and ECOG PS 0–2 were treated with pico, 150 mg/m2 iv over1–2 hrs, q 21 days. Tumor response was assessed q 6 wks. Adverse events (AEs) were graded using the NCI CTCAE. Results: 77 pts received pico (45 refractory, 27 resistant, 5 sensitive). The median number of cycles received was 2 (mean = 2.9). The most frequently reported AEs of any severity were thrombocytopenia (39% of pts), anemia (35%), neutropenia (22%), nausea (20%), emesis (14%) and dyspnea (25%). Neutropenic fever occurred in 1 pt; there were no treatment related deaths. One pt had grade 3 neuropathy; there was no grade 3 or 4 ototoxicity or nephrotoxicity. Median overall survival is 28.1 (95% CI = 26–37) wks. Median progression free survival is 9.3 (95% CI = 7–12) wks. Of 63 pts with at least 1 post-treatment assessment of disease status, 33 (52%) had stable disease. Conclusion: Median survival compares favorably with other therapeutic options and toxicity is reduced in pico treated SCLC pts who have failed prior plat-containing first-line chemo or who have progressed within 180 days of first-line chemo. A phase III trial to confirm these results has been initiated. No significant financial relationships to disclose.

Phase III randomized trial of pegylated liposomal doxorubicin (PLD) plus carboplatin versus carboplatin in platinum-sensitive (PS) patients with recurrent epithelial ovarian or peritoneal carcinoma after failure of initial platinum-based chemotherapy: Southwest Oncology Group Protocol S0200

2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 5551-5551 ◽  
Author(s):  
D. S. Alberts ◽  
P. Y. Liu ◽  
S. Wilczynski ◽  
M. Clouser ◽  
A. Lopez ◽  
...  
Keyword(s):  
Overall Survival ◽  
Pegylated Liposomal Doxorubicin ◽  
Progression Free Survival ◽  
Response Rates ◽  
Phase Iii ◽  
First Line ◽  
Free Survival ◽  
Platinum Based Chemotherapy ◽  
Carboplatin Auc ◽  
Patient Accrual

5551 Background: There is a continuing debate over the role of combination, platinum-based chemotherapy for PS, recurrent ovarian cancer (OC). Although this phase 3 trial was closed prematurely by the SWOG Data Safety and Monitoring Committee (DSMC) due to slow patient accrual, it provided provocative results nonetheless. Methods: Patients with recurrent stage III or IV OC, with a progression-free and platinum-free interval of 6- 24 months after completion of first-line platinum-based chemotherapy, and up to 12 courses of non-platinum containing chemotherapy or biologic therapy as consolidation treatment after the first-line regimen were eligible and observed for progression-free survival (PFS) and overall survival (OS). Patients were randomized to either IV PLD (30 mg/m2) plus IV carboplatin (AUC=5 mg/mL × min) once every 4 weeks (PLD arm) or IV carboplatin (AUC=5mg/ML × min) once every four weeks alone. Results: The PLD arm enrolled 31 patients and the carboplatin alone arm enrolled 30 for a total of 61 patients out of the 900 planned. The response rates were 67% (18/27) for the PLD arm and 32% (9/28) for the carboplatin only arm (Fisher’s exact p=0.02). The estimated median PFS on the PLD arm was 12 months and 8 months on the carboplatin only arm. The estimated median OS on the PLD arm was 26 months and 18 months on the carboplatin only arm (p=0.02). 26% of the patients on the PLD arm reported grade 4 toxicities, all hematological in nature. Conclusions: Although this study was closed early, because of slow patient accrual the results for the PLD arm are intriguing for response rates, median progression-free survival and overall survival. These data suggest that there may be an advantage to the PLD plus carboplatin combination treatment in patients with PS, recurrent disease. No significant financial relationships to disclose.

Final results of After-6 protocol 1: A phase III trial of observation versus 6 courses of paclitaxel (Pac) in advanced ovarian cancer patients in complete response (CR) after platinum-paclitaxel chemotherapy (CT)

2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 5505-5505 ◽  
Author(s):  
P. F. Conte ◽  
G. Favalli ◽  
A. Gadducci ◽  
D. Katsaros ◽  
P. L. Benedetti Panici ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Cancer Patients ◽  
Survival Rates ◽  
Advanced Ovarian Cancer ◽  
Stage Iv ◽  
Experimental Treatment ◽  
Progression Free Survival ◽  
Phase Iii ◽  
First Line ◽  
Absolute Increase

5505 Background: The majority of advanced ovarian cancer patients (pts) in CR after debulking surgery and Platinum/Paclitaxel will eventually relapse. Role of maintenance CT is still questionable even if a SWOG/GOG trial has shown an improved progression free survival (PFS) with 12 vs 3 cycles of maintenance Pac. In March 1999, the After 6 Italian Cooperative Group initiated a phase III study to determine if maintenance Pac could prolong PFS in pts with a clinical (cCR) or pathological CR (pCR) after first line CT Methods: Pts with advanced ovarian cancer in cCR or pCR after 6 cycles of Platinum/Paclitaxel, were randomised to observation or 6 cycles of Pac 175 mg/sqm iv q 3 wks. Primary end point: PFS; secondary end points: overall survival (OS) and toxicities. Planned sample size: 250 pts to detect a 15% absolute increase in 2-yr PFS. Results: From 03/99 to 07/06, 200 pts were randomised. Due to the low accrual rate, an unplanned interim analysis of futility according to the Bayesian approach was performed. Main patient characteristics: median age 58 yrs, median PS 0 (neurotoxicity ≥ G 2 was an exclusion criteria), stage IIb/IIc 15%, stage III 79%, stage IV 6%; 105 pts (52.5%) were in pCR. 14% of pts randomised to observation received Pac; 22% of pts randomised to Pac stopped treatment after 2–5 cycles (progression or death: 3 pts; toxicity: 9 pts; refusal: 7 pts; others: 3 pts). A G ≥ 2 neurotoxicity was reported in 25% of pts treated with Pac; other toxicities were mild. After a median follow up of 44 months, 94 pts (47%) have relapsed and 42 pts (21%) died. Median PFS were 34 and 34.5 months in observation and Pac arm respectively; 3-yr OS was 88% in observation and 78% in Pac arm. Irrespectively of treatment arm, median PFS was 34.4 months for pts with pCR and 24.5 months for those with cCR; 3-yr survival rates were 87% and 79% respectively (p=0.04). Conclusions: Six courses of maintenance Pac do not prolong PFS or OS in pts in CR after first line platinum/paclitaxel. Irrespectively of assigned treatment, the outcome of these pts is more favourable than previously reported and significantly better in the pCRs. Maintenance CT remains an experimental treatment that should be tested in pts at high risk of relapse. [Table: see text]

Randomized phase III trial of gemcitabine and cisplatin versus gemcitabine alone in patients with advanced non-small cell lung cancer (NSCLC) and a performance status (PS) 2: CAPPA-2 study.

2013 ◽  
Vol 31 (15_suppl) ◽  
pp. 8066-8066
Author(s):  
Alessandro Morabito ◽  
Vittorio Gebbia ◽  
Saverio Cinieri ◽  
Maria Grazia Viganò ◽  
Roberto Bianco ◽  
...  
Keyword(s):  
Advanced Nsclc ◽  
Performance Status ◽  
Single Agent ◽  
Stage Iv ◽  
Phase Iii ◽  
Line Treatment ◽  
First Line ◽  
Platinum Based Chemotherapy ◽  
Nsclc Patients ◽  
First Line Treatment

8066 Background: Platinum-based chemotherapy (CT) is the standard treatment for patients (pts) with advanced NSCLC, but the evidence of its efficacy among ECOG PS2 pts is weak, because these pts are usually excluded from clinical trials; concern exists about tolerability and feasibility of standard CT in these pts. No prospective randomized trial has tested the addition of cisplatin to single-agent CT in pts with advanced NSCLC and PS2. Methods: CAPPA-2 was a multicentre, randomized phase III study for first-line treatment of PS2 pts with advanced NSCLC. Patients, aged 18-70, were eligible if they had stage IV or IIIB with malignant pleural effusion or metastatic supraclavicular nodes (TNM VI ed.) and adequate organ function. Patients in standard arm received gemcitabine 1,200 mg/m2 dd1 and 8.Patients in experimental arm received cispaltin 60 mg/m2 d1 plus gemcitabine 1,000 mg/m2 dd1 and 8. All treatments were repeated q3w, up to 4 cycles, unless disease progression or unacceptable toxicity. Primary endpoint was overall survival (OS). To have 80% power of detecting hazard ratio (HR) 0.71, corresponding to an increase in median OS from 4.8 to 6.8 months, 285 deaths were required. Results: The study was stopped in June 2012 after the enrolment of 57 pts, due to the slow accrual and the report of positive results from a similar study. Median OS was 3.0 months with single-agent gemcitabine and 5.9 months with cisplatin + gemcitabine (HR 0.52, 95% CI 0.28-0.98, p=0.039). Combination CT produced longer PFS (median 1.7 vs. 3.3 months, HR 0.49, 95% CI 0.27-0.89, p=0.017) and higher response rate (4% vs. 18%, p=0.19), without substantial increase in toxicity. Conclusions: Addition of cisplatin to single-agent gemcitabine improves survival as first-line treatment of PS2 patients with advanced NSCLC. Clinical trial information: NCT00526643.

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.

Phase III Study of Pemetrexed in Combination With Cisplatin Versus Cisplatin Alone in Patients With Malignant Pleural Mesothelioma

2003 ◽  
Vol 21 (14) ◽  
pp. 2636-2644 ◽  
Author(s):  
Nicholas J. Vogelzang ◽  
James J. Rusthoven ◽  
James Symanowski ◽  
Claude Denham ◽  
E. Kaukel ◽  
...  
Keyword(s):  
Folic Acid ◽  
Survival Time ◽  
Median Survival ◽  
Malignant Pleural Mesothelioma ◽  
Median Survival Time ◽  
Response Rates ◽  
Phase Iii ◽  
Vitamin B ◽  
Pleural Mesothelioma ◽  
Time To Progression

Purpose: Patients with malignant pleural mesothelioma, a rapidly progressing malignancy with a median survival time of 6 to 9 months, have previously responded poorly to chemotherapy. We conducted a phase III trial to determine whether treatment with pemetrexed and cisplatin results in survival time superior to that achieved with cisplatin alone. Patients and Methods: Chemotherapy-naive patients who were not eligible for curative surgery were randomly assigned to receive pemetrexed 500 mg/m2 and cisplatin 75 mg/m2 on day 1, or cisplatin 75 mg/m2 on day 1. Both regimens were given intravenously every 21 days. Results: A total of 456 patients were assigned: 226 received pemetrexed and cisplatin, 222 received cisplatin alone, and eight never received therapy. Median survival time in the pemetrexed/cisplatin arm was 12.1 months versus 9.3 months in the control arm (P = .020, two-sided log-rank test). The hazard ratio for death of patients in the pemetrexed/cisplatin arm versus those in the control arm was 0.77. Median time to progression was significantly longer in the pemetrexed/cisplatin arm: 5.7 months versus 3.9 months (P = .001). Response rates were 41.3% in the pemetrexed/cisplatin arm versus 16.7% in the control arm (P < .0001). After 117 patients had enrolled, folic acid and vitamin B12 were added to reduce toxicity, resulting in a significant reduction in toxicities in the pemetrexed/cisplatin arm. Conclusion: Treatment with pemetrexed plus cisplatin and vitamin supplementation resulted in superior survival time, time to progression, and response rates compared with treatment with cisplatin alone in patients with malignant pleural mesothelioma. Addition of folic acid and vitamin B12 significantly reduced toxicity without adversely affecting survival time.

Phase III Trial of Chemotherapy Plus Radiotherapy Compared With Radiotherapy Alone for Pure and Mixed Anaplastic Oligodendroglioma: Intergroup Radiation Therapy Oncology Group Trial 9402

2006 ◽  
Vol 24 (18) ◽  
pp. 2707-2714 ◽  
Author(s):  
Gregory Cairncross ◽  
Brian Berkey ◽  
Edward Shaw ◽  
Robert Jenkins ◽  
Bernd Scheithauer ◽  
...  
Keyword(s):  
Median Survival ◽  
Radiation Therapy Oncology Group ◽  
Progression Free Survival ◽  
Phase Iii ◽  
Anaplastic Oligodendroglioma ◽  
Allelic Loss ◽  
Survival Times ◽  
Free Survival ◽  
The Status ◽  
Grade 3

Purpose Anaplastic oligodendroglioma (AO) and anaplastic oligoastrocytoma (AOA) are treated with surgery and radiotherapy (RT) at diagnosis, but they also respond to procarbazine, lomustine, and vincristine (PCV), raising the possibility that early chemotherapy will improve survival. Furthermore, better outcomes in AO have been associated with 1p and 19q allelic loss. Patients and Methods Patients with AO and AOA were randomly assigned to PCV chemotherapy followed by RT versus postoperative RT alone. The primary end point was overall survival. The status of 1p and 19q alleles was assessed by fluorescence in situ hybridization. Results Two hundred eighty-nine eligible patients were randomly assigned to either PCV plus RT (n = 147) or RT alone (n = 142). At progression, 80% of patients randomly assigned to RT had chemotherapy. With 3-year follow-up on most patients, the median survival times were similar (4.9 years after PCV plus RT v 4.7 years after RT alone; hazard ratio [HR] = 0.90; 95% CI, 0.66 to 1.24; P = .26). Progression-free survival time favored PCV plus RT (2.6 years v 1.7 years for RT alone; HR = 0.69; 95% CI, 0.52 to 0.91; P = .004), but 65% of patients experienced grade 3 or 4 toxicity, and one patient died. Patients with tumors lacking 1p and 19q (46%) compared with tumors not lacking 1p and 19q had longer median survival times (> 7 v 2.8 years, respectively; P ≤ .001); longer progression-free survival was most apparent in this subset. Conclusion For patients with AO and AOA, PCV plus RT does not prolong survival. Longer progression-free survival after PCV plus RT is associated with significant toxicity. Tumors lacking 1p and 19q alleles are less aggressive or more responsive or both.

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