Safety and efficacy analysis by histology of weekly nab-paclitaxel in combination with carboplatin as first-line therapy in patients (pts) with advanced non-small cell lung cancer (NSCLC).

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. 7592-7592 ◽  
Author(s):  
Markus Frederic Renschler ◽  
Isamu Okamoto ◽  
Jeremy K. Hon ◽  
Vera Hirsh ◽  
Shaker R. Dakhil ◽  
...  
Keyword(s):  
Advanced Nsclc ◽  
Phase Iii ◽  
Positive Trend ◽  
First Line ◽  
Phase Iii Trial ◽  
Efficacy Analysis ◽  
First Line Therapy ◽  
Line Therapy ◽  
Grade 3 ◽  
And Gender

7592 Background: Treatment of advanced NSCLC differs by histology, with fewer options and poorer outcomes in pts with squamous histology. In a phase III trial of nab-paclitaxel (nab-P, 130 nm albumin-bound paclitaxel particles) + carboplatin (C) vs solvent-based paclitaxel (sb-P) + C, the primary endpoint of ORR was significantly improved from 25% to 33%, p = 0.005, with a 1-month improvement in OS (p = NS) and improved safety. This analysis evaluated efficacy and safety by histology. Methods: Pts with untreated stage IIIB/IV NSCLC were randomized 1:1 (stratified by age, histology, region, stage, and gender) 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 PFS were determined by blinded centralized review. Results: In squamous pts, nab-P/C produced a significantly higher ORR (41% vs 24%, p < 0.001), similar PFS (5.6 vs 5.7 mo, HR: 0.865) and >1-month improvement in OS (10.7 vs 9.5 mo, HR: 0.890) vs sb-P/C (Table). nab-P/C was as effective as sb-P/C in nonsquamous pts for ORR (26% vs 25%, p = 0.808), PFS (6.9 vs 6.5 mo, HR: 0.933), and OS (13.1 vs 13.0 mo, HR: 0.950). In both squamous and nonsquamous pts, nab-P/C vs sb-P/C produced lower rates of grade 3/4 neuropathy (3% vs 11% and 3% vs 12%, respectively, p < 0.001 both), neutropenia (43% vs 51%, p = NS, and 50% vs 63%, p = 0.008), and higher but manageable rates of anemia (27% vs 4% and 28% vs 9%, p < 0.001 both) and thrombocytopenia (21% vs 7% and 16% vs 11%, p < 0.001 both). Conclusions: In pts with advanced NSCLC, nab-P/C demonstrated a favorable risk-benefit profile as a first-line therapy regardless of histology. Significantly improved ORR and a positive trend in OS were observed in pts with squamous histology. [Table: see text]

Gemcitabine plus erlotinib followed by capecitabine versus capecitabine plus erlotinib followed by gemcitabine: Interim toxicity analysis of a multicenter, randomized, cross-over phase III trial of the Arbeitsgemeinschaft Internistische Onkologie (AIO)

2009 ◽  
Vol 27 (15_suppl) ◽  
pp. 4604-4604
Author(s):  
V. Heinemann ◽  
U. Vehling-Kaiser ◽  
D. Waldschmidt ◽  
E. Kettner ◽  
A. Marten ◽  
...  
Keyword(s):  
Phase Iii ◽  
Cytostatic Drug ◽  
Line Treatment ◽  
Toxicity Data ◽  
First Line ◽  
Phase Iii Trial ◽  
First Line Therapy ◽  
Line Therapy ◽  
Grade 3 ◽  
Dose Reductions

4604 Background: To date, only limited toxicity data are available for the combination of erlotinib (E; 150 mg/d) with either gemcitabine (G) or capecitabine (C) as first-line therapy for advanced pancreatic cancer (PC). Methods: Within a prospective multicenter phase III trial, 281 patients (pts) with histologically confirmed advanced exocrine PC were randomly assigned to first-line treatment with either C (2000 mg/m2/d, d1–14 q3w) plus E (150 mg/d, arm A) or G (1000 mg/m2 over 30 min weekly x 7, then d1, 8, 15 q4w) plus E (150 mg/d, arm B). In case of treatment-failure (e.g. disease progression or toxicity), pts were “crossed-over” to second-line treatment with the comparator cytostatic drug without E. The primary study endpoint was time to treatment failure of second-line therapy (TTF2). Results: While the trial has completed recruitment, toxicity data (secondary endpoint) are available from the first 127 randomized pts. Sixty pts were randomized to arm A (55% male, 83% metastatic PC), 67 pts to arm B (55% male, 82% metastatic PC); median age was 64 years. During first-line therapy, pts received a median number of 3 treatment cycles (range 0–13) in both arms; overall 456 treatment cycles were applied (arm A: 218, arm B: 238). Regarding chemotherapy, a treatment delay was observed in 12% of the cycles in arm A and in 22% of the cycles in arm B. Dose reductions of the cytostatic drug were performed in 18% and 27% of treatment cycles, respectively. E dose reductions were performed in 6% and 11% of all cycles. Grade 3/4 hematological toxicity was <15% in both arms; in arm A, grade 3/4 diarrhea was observed in 9% of pts (arm B: 7%), grade 3/4 skin rash in 4% (12%) and grade 3/4 hand-foot syndrome in 7% (0%), respectively. Nine pts in arm A (7 of them due to PC) and 8 pts in arm B (6 due to PC) died within 60 days after randomization. Conclusion: G/E and C/E were both tolerated well and toxicity was manageable. This first analysis suggests that treatment with E 150 mg/d is feasible in combination with G or C. [Table: see text]

Results of a randomized, phase III trial of nab-paclitaxel (nab-P) and carboplatin (C) compared with cremophor-based paclitaxel (P) and carboplatin as first-line therapy in advanced non-small cell lung cancer (NSCLC).

2010 ◽  
Vol 28 (18_suppl) ◽  
pp. LBA7511-LBA7511 ◽  
Author(s):  
M. A. Socinski ◽  
I. N. Bondarenko ◽  
N. A. Karaseva ◽  
A. Makhson ◽  
I. Vynnichenko ◽  
...  
Keyword(s):  
Primary Endpoint ◽  
Safety Profile ◽  
Advanced Nsclc ◽  
Dose Intensity ◽  
Phase Iii ◽  
First Line ◽  
Phase Iii Trial ◽  
First Line Therapy ◽  
Highly Active ◽  
Line Therapy

LBA7511 Background: Platinum-based doublet therapy in NSCLC, regardless of the combination used, reached a therapeutic plateau. PC produced 15-25% overall response (ORR, Kelly 2001; Sandler 2006; Schiller 2002). Albumin-bound paclitaxel, nab-P, utilizes the albumin receptor (gp60)/caveolin-1 (CAV1) pathway achieving high intratumoral paclitaxel accumulation (Desai 2006), which may have contributed to a 48% ORR observed with nab-PC in NSCLC (Stroyakovsky, 2009). This phase III trial studied the efficacy of nab-PC vs. PC in advanced NSCLC of all histologic types. Methods: First-line stage IIIB or IV NSCLC pts (ECOG 0/1) were randomized to C AUC6 q3w and either nab-P 100 mg/m2 qw w/o premed (n = 521) or P 200 mg/m2 q3w with premed (n = 531). Primary endpoint: ORR by independent radiologic review (IRR). Results: Baseline and histologic characteristics were well balanced. Dose intensity of paclitaxel was higher in nab-PC vs. PC (82 vs. 65 mg/m2/wk). nab-PC was superior to PC both by IRR (33 vs. 25%, p=0.005), a 31% improvement (1.31 response ratio [RR], 95% CI: 1.08, 1.59), and by investigator review (37 vs. 30%, p=0.008), a 26% improvement (1.26 RR, CI: 1.06, 1.50). Histologic analysis showed significantly improved ORR for nab-PC (n = 228) vs. PC (n = 221) in squamous cell carcinoma (SQC) pts (41 vs. 24%, p<0.001, IRR), a 67% improvement (1.67 RR, CI: 1.26, 2.21). nab-PC was as effective as PC in nonSQC pts (ORR 26 vs. 25%). nab-PC was well tolerated, with significantly improved safety profile vs. PC despite higher paclitaxel dose delivered (1,338 vs. 1,100 mg/m2). Conclusions: The primary endpoint was met, with significantly improved ORR and safety profile of nab-PC vs. PC as first-line therapy for advanced NSCLC. nab-PC was highly active in the SQC subset, which may in part be attributed to the aberrant CAV1 overexpression in SQC (Yoo 2003) and the high intratumoral accumulation of nab-P via the gp60-CAV1 pathway. [Table: see text] [Table: see text]

Doxorubicin and Paclitaxel Versus Fluorouracil, Doxorubicin, and Cyclophosphamide as First-Line Therapy for Women With Metastatic Breast Cancer: Final Results of a Randomized Phase III Multicenter Trial

2001 ◽  
Vol 19 (6) ◽  
pp. 1707-1715 ◽  
Author(s):  
Jacek Jassem ◽  
Tadeusz Pieńkowski ◽  
Anna Płuzańska ◽  
Svetislav Jelic ◽  
Vera Gorbunova ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Overall Survival ◽  
Metastatic Breast Cancer ◽  
Metastatic Breast ◽  
Phase Iii ◽  
Time To Progression ◽  
First Line ◽  
First Line Therapy ◽  
Line Therapy ◽  
Grade 3

PURPOSE: This phase III trial compared the efficacy and safety of doxorubicin and paclitaxel (AT) to 5-fluorouracil, doxorubicin, and cyclophosphamide (FAC) as first-line therapy for women with metastatic breast cancer. PATIENTS AND METHODS: A total of 267 women with metastatic breast cancer were randomized to receive either AT (doxorubicin 50 mg/m2 followed 24 hours later by paclitaxel 220 mg/m2) or FAC (5-fluorouracil 500 mg/m2, doxorubicin 50 mg/m2, cyclophosphamide 500 mg/m2), each administered every 3 weeks for up to eight cycles. Patients had to have measurable disease and an Eastern Cooperative Oncology Group performance status of 0 to 2. Only one prior non–anthracycline, nontaxane-containing adjuvant chemotherapy regimen was allowed. RESULTS: Overall response rates for patients randomized to AT and FAC were 68% and 55%, respectively (P = .032). Median time to progression and overall survival were significantly longer for AT compared with FAC (time to progression 8.3 months v 6.2 months [P = .034]; overall survival 23.3 months v 18.3 months [P = .013]). Therapy was generally well-tolerated (median of eight cycles delivered in each arm). Grade 3 or 4 neutropenia was more common with AT than with FAC (89% v 65%; P < .001); however, the incidence of fever and infection was low. Grade 3 or 4 arthralgia and myalgia, peripheral neuropathy, and diarrhea were more common with AT, whereas nausea and vomiting were more common with FAC. The incidence of cardiotoxicity was low in both arms. CONCLUSION: AT conferred a significant advantage in response rate, time to progression, and overall survival compared with FAC. Treatment was well-tolerated with no unexpected toxicities.

Comparison of the Efficacy and Toxicity of Fludarabine (F) in First Line Therapy of Younger Versus Elderly Patients (Pts) with Advanced Chronic Lymphocytic Leukemia (CLL): Results of a Meta-Analysis of Two Phase III Trials of the German CLL Study Group (GCLLSG).

Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 717-717 ◽  
Author(s):  
Barbara F. Eichhorst ◽  
Raymonde Busch ◽  
Clemens M. Wendtner ◽  
Michael Hallek ◽  
Keyword(s):  
Age Groups ◽  
The Elderly ◽  
Phase Iii ◽  
First Line ◽  
Two Phase ◽  
First Line Therapy ◽  
Line Therapy ◽  
Phase Iii Trials ◽  
Binet Stage ◽  
Grade 3

Abstract Introduction: F based regimen have become the standard treatment in CLL at least in younger pts. However, in elderly pts chlorambucil is still frequently used since it is easy to administer and has less side effects. Here we compare the efficacy and toxicity of F administered to younger pts and elderly pts treated between 1999 and 2004 within two phase III trials of GCLLSG. Patients: 362 pts (median age 59 [range 37–65] years) were randomized to F (n=182) or F plus cyclophosphamide (n=180) within the CLL4 trial. 191 elderly pts (median age 71 [range 65–79] years) were treated with F (92 pts) or chlorambucil (99 pts) within the CLL5 protocol. Inclusion criteria were identical in both trials except for age limits. All pts were previously untreated and in advanced stage Binet C or Binet B with symptoms which require therapy or Binet A with severe B-symptoms. In both studies the F regimen consisted of 30 mg/m2/day (d) IV for 5 consecutive days, every 28 d for up to 6 cycles. Anti-infective prophylaxis and growth factors were not given routinely in both trials. Results: Most of patients in both age groups were in Binet stage B (54% of the younger pts and 52% of the elderly), 35% in each age group were in Binet stage C, 11% and 13% respectively in Binet stage A. No significant difference in the main clinical features was observed except for a higher incidence of concomitant disease in the elderly (61% versus 36%, p=0.001). A mean number of 5.2 F courses was administered in the CLL4 trial and 4.9 courses in the CLL5 trial. The mean administered cumulative dose of F per pt was lower in the elderly pts (1076 mg vs. 1194 mg, p= 0.05). Overall response rates were similar in both arms, with 82.9% in the younger group and 85.7% in the elderly. The complete remission rate was 6.7% in the younger patients and 10.4% in the elderly (p= 0.3). After a follow up time of 24 months (mo) the progression-free survival (PFS) was significantly shorter in the elderly group with 18.7 mo compared to 19.8 mo in the younger group after 22 mo observation time (p=0.03). The overall survival (OS) was significantly impaired in elderly pts as well (29 mo versus median not reached, p&lt;0.001). Progressive disease was the main cause of death in both age groups. In each group 3 treatment related deaths occurred due to infection or hemolysis. The incidence of side effects was similar in both age groups. Severe, CTC grade 3 and 4, myelosuppression occurred in 39% of the younger and 41% of the elderly pts. No difference in the rate of leukocytopenia, thrombocytopenia or anemia was oberved as well. The incidence rate and severity of infections was similar in both groups (24% vs. 32% all and 8.7% vs. 6.9% CTC grade 3 and 4). The incidence of second neoplasia was significantly higher in the elderly pts (2.2% vs. 12.2%, p=0.001). In comparison the prevalence rate of neoplasia in the U.S. population peaks at 11% in the age group of 70–79 (SEER cancer statistic review: 1972–2002). Conclusion: F is a well tolerated treatment regimen in first line therapy of elderly pts with CLL. Response rates were similar in both age groups. PFS and OS were significantly shorter in the elderly population. The incidence of second neoplasia was significantly higher in the elderly pts, but is only slightly increased in comparison to the normal population.

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