A phase II trial of thalidomide (T), irinotecan (I) and gemcitabine (G) in chemonaive patients with advanced non-small cell lung cancer (NSCLC)

2006 ◽  
Vol 24 (18_suppl) ◽  
pp. 17068-17068
Author(s):  
A. R. Jazieh ◽  
R. Komrokji ◽  
S. Patil ◽  
D. Flora ◽  
M. Knapp ◽  
...  
Keyword(s):  
Phase Ii ◽  
Advanced Nsclc ◽  
Survival Rates ◽  
Stage Iv ◽  
Thromboembolic Events ◽  
Early Withdrawal ◽  
Common Grade ◽  
Grade 3 ◽  
Ecog Ps ◽  
Lost To Follow Up

17068 Background: Chemotherapy with platinum based doublets provides only a modest benefit in advanced NSCLC with a median overall survival (OS) of 8 months and 1-year survival rate of 33% (Schiller JH et al, N Engl J Med 2002). We performed a phase II study to determine the efficacy of thalidomide, an immunomodulatory agent with antiangiogenic activity, in combination with chemotherapy in patients with advanced NSCLC. Methods: Chemonaive patients with stage IIIB/IV NSCLC with ECOG PS≤ 2 and adequate organ function were treated with G (1000 mg/m2) and I (100 mg/m2) IV on days 1 and 8 of a 21 day cycle. Patients also received T (200 mg orally with escalation as tolerated to a maximum of 400 mg daily). Therapeutic anticoagulation with coumadin was given to the last 11 patients. Results: Twenty four patients were enrolled: median age 57 years (41–76); M:F=17:7; ECOG PS 0/1/2=13/7/3; stage IV: IIIB= 21:3 and CNS involvement: 6. Two pts died before treatment, 1 was ineligible and 1 was lost to follow up. The remaining 20 pts received a median of 4 treatment cycles (range 1–6). The regimen was generally well tolerated and the most common grade 3–4 toxicities encountered were: diarrhea (4); pneumonia (3) and thromboembolic events (3). There were no thromboembolic events after anticoagulation was initiated. Two patients (10%) experienced partial response, 14 (70%) experienced stable disease, 1 had progressive disease. Three patients (15%) were not evaluable for response due to early withdrawal. The median OS was 10.8 months (range 0.6–37+) and 1-year and 2-year survival rates were 37% and 16%, respectively. The median time to progression was 3.6 months (range 0.2–11+). Conclusions: The combination of thalidomide and chemotherapy is reasonably well tolerated and active in advanced NSCLC as evidenced by good OS and 1- and 2-year survival rates. The addition of thalidomide to a non-platinum based regimen appears to compare favorably to the results of the traditional platinum based doublets. [Table: see text]

A phase II trial of weekly cisplatin and docetaxel in advanced non-small cell lung cancer (NSCLC)

2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 18150-18150
Author(s):  
M. A. Sovak ◽  
S. Lutzker ◽  
L. Guensch ◽  
M. Joyce ◽  
S. Schwartz ◽  
...  
Keyword(s):  
Phase Ii ◽  
Advanced Nsclc ◽  
Significant Risk ◽  
Stage Iv ◽  
Median Number ◽  
Stage Iv Disease ◽  
Low Incidence ◽  
Grade 3 ◽  
Ecog Ps ◽  
Weekly Cisplatin

18150 Background: Every 3-week cisplatin doublets used to treat advanced NSCLC carry a significant risk of renal and other toxicities and can be difficult for patients with co-morbidities. To reduce these toxicities, we conducted a phase II study to evaluate the efficacy and toxicity of weekly cisplatin and docetaxel in advanced NSCLC. Methods: Eligibility included patients with advanced or recurrent NSCLC, ECOG PS of 0–1, and no prior chemotherapy for metastatic disease. This Cancer Institute of New Jersey network, single stage phase II clinical trial was designed to give 3 weekly doses of cisplatin at 25 mg/m2 and docetaxel at 35 mg/m2, followed by 1 week of rest, for a total of 6 cycles of therapy. Toxicity was monitored weekly, and disease evaluation was performed every 2 cycles. The primary endpoint was response rate (RR); secondary endpoints included time to progression (TTP), median and 1-year survival. Results: From 12/03 to 11/06, 36 patients were enrolled so far. The median age of patients is 63 (range 47–78), the majority is white (n=33), 29 have stage IV disease, and half (n=18) are women. Fourteen have an ECOG PS=0 and 22 with PS=1. Histologic subtypes are: adenocarcinoma (n=24), NSCLC NOS (n=7), squamous (n=5). Eleven patients received = 4 cycles of therapy; median number of cycles delivered is 2.5. Reasons for treatment discontinuation include completion of therapy (n=5), progression of disease (n=16), adverse events (n=8), and patient preference (n=4). Three patients continue on therapy at this time. No complete responses were yet observed; 8 patients (22%) achieved a partial response; 10 patients had stable disease, 10 patients progressed, and 8 came off study before first disease evaluation. Median TTP was 3.1 months (mo) (95% CI 2, 5.5), median survival is 8.3 mo (95% CI 5,16.2) and 1-year survival is 39% (95% CI 20, 57). Most toxicities were mild but also included neutropenia (grade 3, n=1; grade 4, n=1), neutropenic fever (n=1), renal toxicity (grade 3, n=2), nausea (grade 3, n=1), fatigue (grade 3, n=3), diarrhea (grade 3, n=4) and metabolic abnormalities (grade 3, n=3). Conclusion: Weekly cisplatin and docetaxel is well tolerated with a low incidence of toxicity and demonstrates activity similar to every 3-week treatment in patients with advanced NSCLC. No significant financial relationships to disclose.

Everolimus in combination with paclitaxel and carboplatin in patients with advanced melanoma: A phase II trial of the Sarah Cannon Research Institute (SCRI).

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. 8556-8556
Author(s):  
Ralph J. Hauke ◽  
Jeffrey R. Infante ◽  
Kent C. Shih ◽  
Mark S. Rubin ◽  
Edward Arrowsmith ◽  
...  
Keyword(s):  
Single Agent ◽  
Stage Iv ◽  
Progression Free Survival ◽  
Advanced Melanoma ◽  
Entire Group ◽  
Combination Regimen ◽  
Eligibility Criteria ◽  
Common Grade ◽  
Grade 3 ◽  
Ecog Ps

8556 Background: The PI3k/AKT pathway is activated in most metastatic melanomas; mTOR is a critical component of this pathway. Everolimus, an mTOR inhibitor, has demonstrated single-agent activity in patients with advanced melanoma. We evaluated the efficacy and toxicity of everolimus in combination with paclitaxel/carboplatin in patients with advanced melanoma. Methods: Eligible patients had stage IV or unresectable stage III melanoma, unselected for braf status, previously untreated with chemotherapy or targeted agents. Previous immunotherapy was allowed. Additional eligibility criteria: ECOG PS 0 or 1; measurable disease; no active brain metastases; adequate bone marrow, kidney, and liver function; informed consent. All patients received paclitaxel 175mg/m2, 1-3 hour IV infusion, and carboplatin AUC 6.0 IV on day 1 of each 21-day cycle. Everolimus 5mg PO was given daily. Patients were evaluated for response every 6 weeks; treatment continued until progression or undue toxicity. Median progression-free survival (PFS) for paclitaxel/carboplatin treatment is 4 months; we looked for a median PFS of 6 months with this novel combination. Results: Seventy patients were treated between 2/2010 and 2/2011; median age 63, 90% had stage IV melanoma. 91% of patients received at least 2 cycles of therapy; median cycles received: 4 (range: 1-25+). Twelve patients (17%) had partial responses; an additional 42 patients (60%) had stable disease at first reevaluation. After a median 13 months of followup, the median PFS for the entire group was 4 months (95% CI: 2.8 – 5.0 months); 96% had progressed during the first 12 months. Median survival was 10 months (95% CI: 7.3 – 10.9 months). Toxicity was as previously described with these agents; neutropenia was the most common grade 3/4 toxicity (27%). Only 3 patients stopped treatment due to toxicity. Conclusions: The addition of everolimus to paclitaxel/carboplatin was feasible and well-tolerated; however, efficacy results were similar to those reported with paclitaxel/carboplatin alone. Further development of this combination regimen for treatment of metastatic melanoma is not recommended.

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.

A single-arm phase II trial to evaluate the combination of cetuximab plus docetaxel, cisplatin, and 5-fluorouracil (TPF) as induction chemotherapy (IC) in patients (pts) with unresectable SCCHN

2009 ◽  
Vol 27 (15_suppl) ◽  
pp. 6015-6015 ◽  
Author(s):  
R. Mesia ◽  
S. Vázquez ◽  
J. J. Grau ◽  
J. A. García-Sáenz ◽  
C. Bayona ◽  
...  
Keyword(s):  
Febrile Neutropenia ◽  
Phase Ii ◽  
Phase Ii Trial ◽  
Objective Response ◽  
Stage Iv ◽  
Stage Design ◽  
Concomitant Boost ◽  
Secondary Neoplasm ◽  
Grade 3 ◽  
Ecog Ps

6015 Background: TPF combination is the new standard IC. Adding cetuximab to PF chemotherapy is superior to PF alone in metastatic disease. We incorporated cetuximab into IC with TPF and subsequent radiotherapy (RT) in unresectable SCCHN. Methods: Phase II trial conducted in 7 Spanish hospitals. Previously untreated pts aged 18–70 yrs, ECOG PS 0–1 with unresectable SCCHN were eligible. Induction comprised T 75mg/m2 day 1, P 75mg/m2 day 1, F 750mg/m2 days 1–5, and cetuximab 250mg/m2 days 1, 8, and 15 (initial dose 400mg/m2 on cycle (C) 1, day 1), repeated every 21 days x 4 C, with prophylactic antibiotics and G-CSF support. Subsequently, pts received accelerated RT with a concomitant boost (69.9Gy) and cetuximab 250mg/m2 weekly. The primary endpoint was the objective response rate (RR) to cetuximab TPF as neoadjuvant therapy. Simon's optimal two-stage design was used to calculate the sample size of 49 evaluable pts. Results: 50 pts were enrolled: median age 54 yrs (33–68); 44 male; all stage IV (T4=31, N2–3=40). Primary sites were: oropharynx, 23; hypopharynx, 16; oral cavity, 5; larynx, 4.41(82%) pts received all 4 cycles of cetuximab TPF; 47 pts received ≥2 C and were evaluable for response using RECIST. 3 pts received <2 C (2 deaths from intercurrent disease and febrile neutropenia, 1 secondary neoplasm diagnosed). The table shows RR. Serious grade 3/4 adverse events (AEs) were: neutropenia 24%; neutropenic fever 20%; infection 6%; thrombocytopenia 4%; diarrhea 12%; hepatotoxicity 4%; hypomagnesemia 2%. Grade 3 AEs were: nausea/vomiting 2%; mucositis 6%; renal failure 4%; asthenia 4%; rash 4%; hypotension 4%. There were 2 AE-related deaths (febrile neutropenia and hepatic insufficiency). Conclusions: The addition of cetuximab to TPF IC in pts with unresectable SCCHN yields a high RR, mainly CR, potentially prolonging survival. Cetuximab TPF combination should be given to pts with good PS with specialized support provided. [Table: see text] [Table: see text]

Phase I study of the IXO regimen, irinotecan (I), capecitabine (X), oxaliplatin (O), as first-line therapy for metastatic colorectal cancer: Final survival results

2009 ◽  
Vol 27 (15_suppl) ◽  
pp. 4082-4082
Author(s):  
J. Maroun ◽  
D. Jonker ◽  
C. Cripps ◽  
R. Goel ◽  
T. Asmis ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Phase I ◽  
Metastatic Colorectal Cancer ◽  
Phase Ii ◽  
Line Treatment ◽  
First Line ◽  
Common Grade ◽  
Grade 3 ◽  
Ecog Ps ◽  
First Line Treatment

4082 Background: This study was designed to determine the dose-limiting toxicity (DLT), maximum tolerated dose (MTD) and efficacy of the IXO regimen when used as first-line treatment for metastatic colorectal cancer (mCRC). Methods: Patients with ECOG PS 0–2, histologically proven, chemo-naïve, non-resectable mCRC were eligible. Phase I starting doses were as follows: I (180 mg/m2 i.v.) d1, X (850 mg/m2 bid orally) d2–15, O (85 mg/m2 i.v.) d1; q3w. Dose escalation (3+3 design) was based on toxicity observed at previous dose levels (DL) until DLT and the MTD were reached. Results: 39 pts (31 male/8 female, median age 58 years, ECOG PS 0–1 in 37, 95%) received a median of 11 cycles (range 1–34) at 8 DLs. 39 pts were evaluable for toxicity. The most common grade 3/4 hematological adverse events (AEs) were granulocytopenia (60%) and fever/febrile neutropenia (18%). The most common grade 3 non-hematological AEs were diarrhea (15%), vomiting (10%), fatigue (8%). No grade 3/4 neuropathy was reported. DLTs: 1 DLT was observed at each of the first 4 DLs, no DLTs at DL5 & 6, 1 at DL7 and 2 at DL8. MTD was reached at DL8. The recommended phase II dose (DL7) is as follows: I (160 mg/m2), X (950 mg/m2), O (100 mg/m2). Efficacy: 38 pts are evaluable for efficacy. The RR is 74% (95% CI 60–89), including 4 CRs, 25 PRs and 6 SDs. The disease control rate is 90% (95% CI 80–100). 10 (26%) pts had subsequent liver surgery with curative intent; 1 had lung resection. Median progression-free survival was 12.3 months (95% CI, 8–17). Overall median survival was 26.4 months (95% CI, 13–36). Conclusions: Diarrhea is the main DLT. Severe neutropenia was of short duration and manageable. The IXO regimen is well tolerated and highly effective as first-line treatment for mCRC. It appears to be particularly effective in downsizing of initially unresectable colorectal cancer liver metastases. A phase II study to confirm the efficacy/safety of IXO in combination with bevacizumab (Avastin) is ongoing. Supported by: Hoffmann La-Roche, Sanofi-Aventis, Pfizer Canada. [Table: see text]

Nivolumab (NIVO) plus ipilimumab (IPI) with two cycles of chemotherapy (chemo) in first-line metastatic non-small cell lung cancer (NSCLC): CheckMate 568 Part 2.

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. 9560-9560
Author(s):  
Justin F. Gainor ◽  
Jeffrey Gary Schneider ◽  
Martin Gutierrez ◽  
James Michael Orcutt ◽  
Gene Grant Finley ◽  
...  
Keyword(s):  
Advanced Nsclc ◽  
Stage Iv ◽  
Hepatic Function ◽  
Primary Endpoints ◽  
Common Grade ◽  
Treatment Naïve ◽  
Checkpoint Inhibitor Therapy ◽  
Grade 3 ◽  
Platinum Doublet

9560 Background: In Part 1 of the phase II CheckMate 568 study (NCT02659059), NIVO + IPI was active and tolerable in patients (pts) with advanced NSCLC. The addition of chemo to dual immune checkpoint inhibitor therapy may further improve initial disease control. We report results from Part 2 of CheckMate 568, which evaluates NIVO + IPI combined with 2 cycles of chemo in pts with advanced treatment-naive NSCLC. Methods: Adult pts with untreated stage IV NSCLC received NIVO 360 mg Q3W + IPI 1 mg/kg Q6W combined with 2 cycles of histology-based platinum-doublet chemo, followed by NIVO + IPI without chemo until disease progression/unacceptable toxicity for ≤ 2 years. The primary endpoints were dose-limiting toxicity (DLT) within the first 9 weeks and safety/tolerability. Treatment was considered safe if ≤ 25% of at least 22 evaluable pts had a DLT. DLTs included but were not limited to: uncontrolled grade 3 non-skin treatment-related adverse events (TRAEs), grade 4 TRAEs, grade 2 treatment-related pneumonitis not resolved within 14 days, and treatment-related hepatic function abnormalities. Results: In total, 36 pts received treatment; 97% of pts completed 2 cycles of chemo combined with NIVO + IPI. Three pts discontinued IPI while continuing NIVO. Minimum follow-up was 14.9 months. Only 1 (3%) pt experienced a DLT (transient, asymptomatic grade 3 AST and ALT elevation) within the first 9 weeks. The elevation occurred on cycle 1, day 21 and resolved 2 weeks later with discontinuation of IPI, delay of NIVO, and treatment with prednisone; chemo was continued throughout and NIVO was restarted thereafter without recurrent toxicity. Grade 3–4 TRAEs occurred in 21 (58%) pts. Eight (22%) pts experienced a TRAE leading to discontinuation, most commonly colitis, encephalopathy, pneumonitis, and arthralgia (each in 2 [6%] pts); these events occurred outside of the 9-week window for DLT assessment. The most common select TRAEs (defined as AEs of potential immunologic causes) were skin related (18 [50%] pts); the most common grade 3–4 select TRAEs were endocrine (3 [8%] pts), skin related, gastrointestinal, and pulmonary (each in 2 [6%] pts). No treatment-related deaths occurred. Updated safety in addition to efficacy data will be presented. Conclusions: In pts with untreated advanced NSCLC, the addition of 2 cycles of platinum-doublet chemo to NIVO + tumor-optimized IPI was tolerable. No unexpected safety signals were observed. Clinical trial information: NCT02659059 .

A Phase II Trial of FM (Fludarabine and Mitoxantrone) Chemotherapy Followed by Yttrium 90 (90Y) Ibritumomab Tiuxetan (Zevalin®) for Previously Untreated Indolent Non-Follicular Lymphoma Patients.

Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 2478-2478
Author(s):  
Pier Luigi Zinzani ◽  
Monica Tani ◽  
Stefano Fanti ◽  
Gerardo Musuraca ◽  
Alessio Perrotti ◽  
...  
Keyword(s):  
Follicular Lymphoma ◽  
Induction Chemotherapy ◽  
Phase Ii ◽  
Safety Data ◽  
Stage Iv ◽  
Stage Iii ◽  
Efficacy And Safety ◽  
Ibritumomab Tiuxetan ◽  
Common Grade ◽  
Grade 3

Abstract We conducted a prospective, single-arm, open-label, non-randomized, multicenter, phase II to evaluate the efficacy and safety of 90Y Ibritumomab Tiuxetan of a novel new approach combining induction chemotherapy with Fludarabine and Mitoxantrone (FM) followed by consolidation with 90Y Ibritumomab Tiuxetan for patients with previously untreated indolent non-follicular lymphoma (indolent non-FL). Patient eligibility was represented by: patients age 18 years or older with biopsy-proven, untreated, bidimensionally measurable stage II, stage III, or stage IV indolent non-FL expressing the CD20 antigen; WHO performance status of 0 to 2. All patients were notified of the investigational nature of this study and signed a written informed consent approved in accordance with institutional guidelines, including the Declaration of Helsinki. The study was approved by the institutional review boards. Patients were treated with standard FM chemotherapy every 28 days for 6 cycles. Patients were restaged 4 to 8 weeks after completion of the sixth cycle of FM chemotherapy. Patients achieving at least a partial response after 6 cycles of FM chemotherapy were eligible for consolidation with 90Y Ibritumomab Tiuxetan provided the granulocyte count was greater than 1500/μL, the platelet count exceeded 100.000/μL, and the bone marrow examination at the completion of FM chemotherapy demonstrated no more than 25% involvement with lymphoma. All patients were to receive a single dose of 90Y Ibritumomab Tiuxetan 14.8 MBq/kg (0.4 mCi/kg) up to a maximum dose of 1184 MBq (32 mCi). At data reporting for this abstract, 29 patients were enrolled and 26 were evaluable for response. Of these 26 patients, all are evaluable for induction chemotherapy FM regimen and 17 of them also are evaluable after 90Y Ibritumomab Tiuxetan treatment. Histologically, 11 had marginal zone lymphoma, 10 had lymphoplasmacytic lymphoma, and 5 had small lymphocytic lymphoma; 10 were male and 16 female; the median age was 61 years (range 45–82); 4 were stage III, and 21 stage IV. After the FM treatment the overall response rate was 81%, including 50% CR and 31% PR. Time to event analyses, including TTP and duration of response are pending further follow-up. Treatment was well tolerated; grade ≥ 3 AEs were seen in 13 patients; the most common grade ≥ 3 AEs was neutropenia. Among the actual 17 evaluable patients subsequentially treated with 90Y Ibritumomab Tiuxetan, 2/4 (50%) patients improved their remission status from PR to CR. The 90Y Ibritumomab Tiuxetan toxicity included grade ≥ 3 hematologic AEs in 15 patients; the most common grade ≥ 3 AEs were neutropenia (10 patients) and thrombocytopenia (15 patients). Transfusions of red cells and/or platelets were given to 6 patients. These preliminary data indicate the feasibility, tolerability, and efficacy of the FM plus 90Y Ibritumomab Tiuxetan regimen for patients with untreated indolent non-FL. Final efficacy and safety data will be presented.

Randomized phase II study of low (100mg) versus intermediate (400mg) doses of thalidomide (Thal) plus DTIC in metastatic melanoma (MM)

2006 ◽  
Vol 24 (18_suppl) ◽  
pp. 8048-8048
Author(s):  
R. Von Moos ◽  
R. Dummer ◽  
R. Inauen ◽  
T. Ruhstaller ◽  
S. Meier ◽  
...  
Keyword(s):  
Phase Ii ◽  
Response Rate ◽  
Performance Status ◽  
Single Agent ◽  
Objective Response ◽  
Haematological Toxicity ◽  
Stage Iv ◽  
Clinical Activity ◽  
Thromboembolic Events ◽  
Grade 3

8048 Background: Single agent DTIC is the standard therapy for MM. In an effort to improve the response rate (DTIC 7–13%), Thal, a molecule with antiangiogenic effect was added in two different dosages to DTIC. Methods: Eligibility: Stage IV MM, ECOG performance status 0–2, no prior treatment with DTIC or Thal. Design: Randomized multicenter phase II Bryant and Day 2-stage optimal design with 20 patients (pats) per arm. Treatment regimens: DTIC 200mg/m2 d1–5 q3w plus Thal (100 versus 400mg per day). Responses were assessed every two cycles. Endpoints: Toxicity, feasibility, response rate (RR) and time to treatment failure (TTF). Results: 26 pats (12 male/ 14 female) at a median age of 58 years (range 24–82) with stage IV melanoma (M1a-2, M1b-2, M1c-22) were enrolled between 2001–2005 and received a median of 4 cycles (1–6). All the pats were evaluated for toxicity, 25 (96%) were assessable for objective response (WHO criteria). The overall response rate of the evaluable patients was 27% (100mg, RR 25%; 400mg, RR 33%), one patient (4%) had a complete response, 6 pats (23%) had a partial response, 11 pats had stable disease (42%), and 7 pats (27%) progressed. The median TTF was 5.2 months. Using NCI 2.0 Common Toxicity Criteria, grade 3 haematological toxicity was 12% (anemia-1, leucopenia-1, thrombocytopenia-1). Cumulative non-haematological toxicity grade 3/4 was 35% including fatigue in 5 pats (all on 400mg Thal arm), thromboembolic events in 2 (1 each treatment arm) and bleeding in 2 (1 cerebral). Polyneuropathy and constipation were a minor problem (no grade 3/4). The 400mg Thal arm was stopped according to the protocol because of intolerable fatigue in 5 out of 6 patients. Two of the first 14 pats suffered from pulmonary embolism. Thromboprophylaxis with low molecular weight heparin (LMWH) was mandatory after an amendment . Thereafter no thromboembolic events were seen but one fatal cerebral bleeding occurred in one patient. Conclusions: 400mg Thal in combination with DTIC was not feasible due to toxicity. 100mg Thal was well tolerated and showed significant clinical activity. Using our low dose Thal regimen prophylactic LMWH is necessary to prevent severe thromboembolic events. No significant financial relationships to disclose.

Customized first-line chemotherapy according to ERCC1 and RRM1 SNPs in advanced NSCLC patients: A phase II study.

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. e18074-e18074
Author(s):  
Francesca Mazzoni ◽  
Fabiana Letizia Cecere ◽  
Giulia Meoni ◽  
Costanza Giuliani ◽  
Andrea Camerini ◽  
...  
Keyword(s):  
Phase Ii ◽  
Advanced Nsclc ◽  
Excision Repair ◽  
Stage Iv ◽  
First Line ◽  
Open Label ◽  
Expression Levels ◽  
Best Response ◽  
Docetaxel Treatment ◽  
Ecog Ps

e18074 Background: Excision repair cross complementing group 1 (ERCC1) and ribonucleotide reductase1 (RRM1) expression levels are predictive of CT efficacy in some malignancies. “Customized” CT has several advantages: (1) pts are more likely to be treated with agents that they will respond to, (2) pts can be spared the toxicity of agents that they are resistant to, (3) effective treatment can be delivered early in the course of disease. Methods: We planned a phase II multicentric open label study in two steps (based on Simon design) to evaluate ERCC1 SNPs (T118C and C8092A) and RRM1 SNPs (-37C>A and -524T>C) in advanced NSCLC pts. Here we report the first step for futility. Pts received first line CT according to the assessed ERCC1 and RRM1 SNPs status and the correlated expression levels: treatment A (low ERCC1 and low RRM1) Cisplatin plus Gemcitabine; treatment B (low ERCC1 and high RRM1) Cisplatin plus Docetaxel; treatment C (high ERCC1 and low RRM1) Gemcitabine plus Docetaxel; treatment D (high ERCC1 and high RRM1) Docetaxel plus Vinorelbine. Results: 42 pts were enrolled from Jan. 2010 to Oct. 201, 40 pts received at least 1 cycle of CT; median age was 66 yrs (range 47-73); 33 pts were males; 23(55%) pts were ECOG PS 0, 19(45%) PS 1; all pts had stage IV; 23(55%) pts had adenoca, 13(31%) squamous, 6(14%) other types; 25(62%) pts received treatment A, 3(8%) treatment B, 11(27%) treatment C, 1(3%) treatment D. As primary end-point we assessed the overall best response: 18(45%) pts achieved PR, 12(30%) SD, 8(20%) PD, 2(5%) pts were not evaluable. Updated information on OS and PFS will be presented. CT was well tolerated, there were no treatment related deaths. Conclusions: We observed an improved RR in this setting of NSCLC pts treated with CT according to ERCC1 and RRM1 SNPs status. We are planning to continue the second step of this trial (total 110 pts).

Lenvatinib combined with dacarbazine versus dacarbazine alone as first-line treatment in patients with stage IV melanoma.

2013 ◽  
Vol 31 (15_suppl) ◽  
pp. 9027-9027 ◽  
Author(s):  
Michele Maio ◽  
Jessica Cecile Hassel ◽  
Michele Del Vecchio ◽  
Alessandro Testori ◽  
Paolo Antonio Ascierto ◽  
...  
Keyword(s):  
Kinase Inhibitor ◽  
Single Agent ◽  
Stage Iv ◽  
Fold Increase ◽  
Circulating Tumor Dna ◽  
Therapeutic Effects ◽  
Common Grade ◽  
Grade 3 ◽  
Ecog Ps ◽  
To Receive

9027 Background: Lenvatinib (E7080; LEN) is an oral, receptor tyrosine kinase inhibitor targeting VEGFR1-3, FGFR1-4, RET, KIT and PDGFRβ . In a phase I study qd dosing of >/= 20mg LEN demonstrated PRs and prolonged SD in patients (pts) with advanced melanoma. Dacarbazine (DTIC) upregulates the proangiogenic factor VEGF and has been shown to confer resistance in melanoma cell lines (Lev, JCO 2004; 22:2092-2100). Treatment of melanoma pts with LEN + DTIC may potentiate the therapeutic effects of DTIC. Methods: This was a phase II study in pts with metastatic melanoma randomized 1:1 to receive LEN (20 mg QD) + DTIC (1000 mg/m2 Q 21 d) or DTIC (1000 mg/m2Q 21 d). Pts were stratified by LDH level and stage IV subclass. Eligible pts were ECOG PS 0/1 and had no prior systemic therapies. BRAF status was determined from circulating tumor DNA. The primary endpoint was PFS by independent assessment. Results: In a modified ITT analysis,a total of 78 of 81 pts were evaluable for efficacy; 59% were male, 59% were Stage IV M1c, 22% had elevated LDH, 29% had prior adjuvant therapy and 49% BRAF wild-type (wt). Most common AEs in the LEN + DTIC arm were hypertension (48%), nausea (38%), constipation (33%), and diarrhea (31%). Most common Grade 3/4 AEs in LEN + DTIC were hypertension (26%) and neutropenia (10%). There were no deaths due to an AE. Median PFS increased in LEN + DTIC compared to DTIC alone (see Table). An improvement in median PFS was observed in BRAFwt pts on the combination. Conclusions: A 2.7-fold increase in the median PFS was observed in pts administered LEN + DTIC compared to single agent DTIC. A 2.5 fold increase in the median PFS was observed in the combination arm in pts with BRAFwt melanoma. The AE profile observed with the LEN + DTIC was consistent with observed LEN monotherapy studies. These data suggest further evaluation of LEN + DTIC in BRAFwt melanoma is warranted. Clinical trial information: NCT01133977. [Table: see text]

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