Randomized, double-blind, placebo-controlled phase II study of carboplatin and paclitaxel with or without vorinostat, a histone deacetylase inhibitor (HDAC), for first-line therapy of advanced non-small cell lung cancer (NCI 7863)

2009 ◽  
Vol 27 (15_suppl) ◽  
pp. 8004-8004
Author(s):  
S. S. Ramalingam ◽  
M. Maitland ◽  
P. Frankel ◽  
A. E. Argiris ◽  
M. Koczywas ◽  
...  
Keyword(s):  
Phase Ii ◽  
Type I Error ◽  
Advanced Nsclc ◽  
Response Rate ◽  
Phase Ii Study ◽  
Performance Status ◽  
Hepatic Function ◽  
Placebo Treatment ◽  
Type I ◽  
Double Blind

8004 Background: Vorinostat, a HDAC inhibitor, enhances paclitaxel and platinum-mediated anti-cancer activity in preclinical studies by enhanced tubulin acetylation and DNA fragmentation respectively. Promising activity with carboplatin (C), paclitaxel (P), and vorinostat in patients with advanced NSCLC in the phase I study (Ramalingam et al, Clin Cancer Res, 2007) prompted this placebo-controlled, randomized phase II study. Methods: Pts. with stage IIIB (wet) or IV NSCLC, performance status (PS) 0/1, no prior therapy and adequate bone marrow, renal and hepatic function were randomized (2:1) for therapy with PC with either vorinostat or placebo. Treatment consisted of C: AUC=6 mg/ml.min; and P 200 mg/m2 both given on day 3 along with either vorinostat (400 mg PO QD) or placebo on days 1–14 of each 3 wk cycle to a maximum of 6 cycles. The estimated sample size to demonstrate a 50% improvement in response rate for vorinostat over placebo was 93 pts. (one-sided P, type I error 10%). Results: Ninety-four pts. were enrolled (vorinostat-64; placebo-32). Pts. baseline characteristics were similar between the two arms (median age 64, male 60%, PS 0 40%, brain mets 16%). Median # cycles: vorinostat-3.5; placebo - 4. The confirmed response rate was superior with vorinostat over placebo (34% vs. 12.5%, P = 0.02). At the time of analysis, the preliminary median PFS for vorinostat and placebo were 5.75 and 4.1 m respectively (ITT). Follow up for survival is ongoing. Common grade 3/4 toxicities (vorinostat vs. placebo): neutropenia (44% vs. 47%); thrombocytopenia (33% vs. 16%); fatigue (13% vs. 3%); hyponatremia (21% vs. 6%); diarrhea (5% vs. 0). Discontinuation from study after cycle 1 was higher with vorinostat (27% vs. 16%). Biomarker studies on baseline tumor tissue and peripheral blood cells are ongoing. Conclusions: Administration of vorinostat with carboplatin and paclitaxel resulted in a significantly superior response rate for pts.with advanced NSCLC. HDAC inhibition is a novel therapeutic strategy for treatment of NSCLC. Supported by ASCO Career Development Award to S.S.Ramalingam, and NCI NO1-CM-62209, NO1-CM-62201, NO1-CM-62208. [Table: see text]

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

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

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

Icotinib and whole brain radiotherapy (WBRT) for patients with brain metastases from non-small cell lung cancer (NSCLC): Preliminary results of a phase II study.

2013 ◽  
Vol 31 (15_suppl) ◽  
pp. e19073-e19073
Author(s):  
Fan Yun ◽  
Zhiyu Huang ◽  
Lei Gong ◽  
Haifeng Yu ◽  
Haiyan Yang ◽  
...  
Keyword(s):  
Brain Metastases ◽  
Phase Ii ◽  
Kinase Inhibitors ◽  
Advanced Nsclc ◽  
Response Rate ◽  
Phase Ii Study ◽  
Whole Brain Radiotherapy ◽  
Phase Iii ◽  
Double Blind ◽  
The Mean

e19073 Background: Epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs), such as gefitinib and erlotinib, have shown efficacy in advanced NSCLC with brain metastases (BM). Icotinib is a new EGFR-TKI. A randomized, double blind phase III trial proved that icotinib was non-inferior to gefitinib in advanced NSCLC. We have conducted a phase II study to evaluate the efficacy and safety of icotinib in combination with WBRT in Chinese NSCLC patients with BM. Methods: From January 2012 to January 2013, 20 patients aged 18-75 years with ECOG PS 0-2 and BM from NSCLC,were recruited regardless of EGFR status. The treatment comprised icotinib 125mg, TID concurrently with WBRT (30Gy/10f/2w). CSF and plasma samples were collected at the same time from 10 patients at least 5 days after icotinib treatment. The concentrations of icotinib in the CSF and plasma were measured by high performance liquid chromatography coupled with tandem mass spectrometry. The primary end point was progression-free survival (PFS) . Additional end points were response rate, safety and CSF concentrations of icotinib. Results: The median PFS was 7.3 months [95% confidence interval (CI) 4. 2-9.8]. Patients with EGFR mutation-positive disease had significantly longer median PFS versus EGFR wild-type disease [NR versus 4.2 months (95% CI 2.9-5.1); P = 0.000]. The CNS response rates were 25% complete response (n=5), 55% partial response (n= 11), 15% stable disease (n=3), and 5% progressive disease (n =1). The overall CNS response rate was 80% (n = 16). The most common adverse events were rash (40.0%), diarrhea (15.0%),nausea (45.0%), vomiting (20.0%), headache (35.0%)and fatigue (45.0%). And no patient experienced grade ≥ 3 toxicity. The mean plasma and CSF concentrations of icotinib were 936.47 ± 503.80 and 8.93 ± 8.01 ng/ml, respectively, and the mean ratio of CSF-plasma concentration was 1.04% ± 0.95. Conclusions: Icotinib was well tolerated and showed promising activity in combination with WBRT in patients with BM from NSCLC. The concentrations of icotinib in CSF were low. Further randomized trials are warranted. Clinical trial information: NCT01514877.

Phase II randomized trial of docetaxel plus cetuximab or bortezomib in patients with advanced NSCLC and performance status (PS) 2—CALGB 30402

2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 7595-7595 ◽  
Author(s):  
R. Lilenbaum ◽  
X. Wang ◽  
L. Gu ◽  
J. Kirshner ◽  
E. Vokes
Keyword(s):  
Phase Ii ◽  
Type I Error ◽  
Advanced Nsclc ◽  
Performance Status ◽  
Stage Iv ◽  
Progression Free Survival ◽  
Hematologic Toxicity ◽  
Type I ◽  
Weekly Schedule ◽  
Male Response

7595 Background: There is no standard treatment for patients (pts) with advanced NSCLC and PS 2. Docetaxel (D) is active and well tolerated on a weekly schedule. Cetuximab (C) and Bortezomib (B) are new agents with activity in NSCLC. We explored these two new combinations in PS 2 pts. Methods: In a multi-center randomized phase II trial, untreated pts with advanced NSCLC and PS 2 were randomized to D 30 mg/m2 d1,8,15 q. 28 days in combination with either C 400 mg/m2 week 1 then 250 mg/m2 weekly, or B 1.6 mg/m2 d1,8,15 q. 28 days for 4 cycles. Pts with CR/PR/SD were allowed to continue C or B until PD. The study was non-comparative and the primary endpoint was progression-free survival (PFS) rate at 6 months. The trial had a type I error of 0.0746 and power of 0.9 to differentiate a 6-mo PFS of <20% vs. >42%. Results: 64 pts were enrolled between 7/05 and 9/06. 5 were ineligible and 3 never received protocol treatment. Results are reported for 55 pts (27 D+C; 28 D+B). Most pts had stage IV adenoCa and 13% had brain metastases. Median age was 70 (range, 35–88) and 65% were male. Response: 10.5% for D+C and 13.6% for D+B. Median PFS was 3.1 mo for D+C and 1.8 mo for D+B. PFS rates at 4 mo (data not yet mature for 6-mo): 33% and 28%, respectively. Median survival: 3.8 mo for D+C and 3.3 mo for D+B. Gr 3/4 hematologic toxicity was 17% in both arms. Gr 3/4 non-heme toxicities were 44% in D+C and 36% in D+B arm. 5 pts died of treatment-related toxicities (3 D+C; 2 D+B). Conclusions: These results confirm the poor prognosis associated with a PS of 2. Based on our preliminary analysis, neither combination produced results that justify further research in this subset of patients. The treatment of PS 2 patients with advanced NSCLC remains a vexing problem and new approaches are urgently needed. No significant financial relationships to disclose.

Bortezomib + gemcitabine (Gem)/carboplatin (Carbo) results in encouraging survival in advanced non-small cell lung cancer (NSCLC): Results of a phase II Southwest Oncology Group (SWOG) trial (S0339)

2006 ◽  
Vol 24 (18_suppl) ◽  
pp. 7017-7017 ◽  
Author(s):  
A. M. Davies ◽  
J. McCoy ◽  
P. N. Lara ◽  
P. H. Gumerlock ◽  
J. Crowley ◽  
...  
Keyword(s):  
Median Survival ◽  
Phase Ii ◽  
Advanced Nsclc ◽  
Response Rate ◽  
Phase Ii Study ◽  
Performance Status ◽  
Single Agent ◽  
Stage Iiib ◽  
Phase Iii ◽  
Survival Times

7017 Background: Bortezomib (PS-341), a small molecule proteasome inhibitor, has single agent activity in NSCLC and potentiates Gem/Carbo in pre-clinical models in a sequence-specific manner (Mortensen, Cancer Chem Pharm, 2004). A phase I trial of Gem/Carbo + PS-341 in patients (pts) with advanced NSCLC yielded an encouraging response rate of 48%. Here we describe the results of a SWOG phase II study of this regimen in advanced NSCLC. Methods: 114 eligible chemonaive stage IV and selected stage IIIB (pleural effusion) NSCLC pts received Gem 1000 mg/m2 on days 1, 8 and Carbo AUC 5 on day 1, followed 1 hour later by PS-341 1.0 mg/m2 on days 1, 4, 8, 11, with cycles repeated every 3 weeks. Non-progressing pts could continue PS-341 alone after 4 cycles. Results: Pt characteristics: Median age: 64 years; Sex M/F = 68/46; Performance status 0/1 = 50/64; stage IIIB/IV = 13/101. Response rate: 20% (95% CI 13–29%); 66% (95% CI 56–75%) had stable disease. At a median follow-up of 13 months, progression free and median survival times were 5 months (95% CI 3.5–5.3) and 11 months (95% CI 8.2–12.5). One-year survival was 46% (95% C.I. 37–55%). Most common grade 3/4 toxicities: neutropenia (52%), thrombocytopenia (63%), and fatigue (13%). Ongoing correlative studies are examining markers of proteasome inhibition (Bcl2 family, NFKB, IKB) and hypoxia (PAI-1, VEGF, OPN, HIF-1) in tumor tissue and surrogate specimens. Conclusions: The 11 month median survival achieved with the addition of PS-341 to Gem/Carbo in this phase II study is unprecedented in prior SWOG trials in advanced NSCLC, and does not appear to be explained by altered patient characteristics. The toxicity profile of this regimen is favorable. A phase III trial of Gem/Carbo ± Bortezomib in advanced stage NSCLC is under development. Supported by CA38926, CA32102. No significant financial relationships to disclose.

Phase II study of cetuximab in combination with carboplatin and docetaxel for patients with advanced/metastatic non-small cell lung cancer (NSCLC)

2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 7643-7643 ◽  
Author(s):  
C. P. Belani ◽  
S. Ramalingam ◽  
M. Schreeder ◽  
R. Steis ◽  
R. Guidice ◽  
...  
Keyword(s):  
Disease Progression ◽  
Phase Ii ◽  
Advanced Nsclc ◽  
Response Rate ◽  
Phase Ii Study ◽  
Performance Status ◽  
Single Agent ◽  
Stage Iiib ◽  
Duration Of Treatment ◽  
Ecog Performance Status

7643 Background: Cetuximab, a chimeric IgG1 monoclonal antibody against the external domain of the epidermal growth factor receptor (EGFR), has demonstrated single-agent activity against NSCLC. When administered in combination with carboplatin and docetaxel, a commonly used regimen for advanced NSCLC, cetuximab exhibits synergistic interaction in preclinical studies. Therefore, we conducted a phase II study to evaluate the efficacy of the combination of cetuximab, carboplatin, and docetaxel for the treatment of advanced NSCLC. Methods: Chemotherapy-naive patients = 18 years with histologically/cytologically confirmed stage IIIB (w/ effusion) or stage IV NSCLC received cetuximab (400 mg/m2 on day 1 and 250 mg/m2 on days 8 and 15) plus docetaxel (75 mg/m2 on day 1) and carboplatin (AUC=6 on day 1) every 21 days for up to 6 cycles. Thereafter, patients without evidence of disease progression (CR/PR/SD) were continued on single-agent cetuximab (250 mg/m2/week) for a maximum of 1 year or until disease progression. The primary endpoint was response rate. Results: 81 patients were enrolled and 76 are evaluable for response. Patient characteristics included: gender male/female, 43/38; median age 63 years (range 42–83); ECOG performance status 0/1/, 31/50; and stage IIIB/IV- 5/76. The median number of cycles administered was 4 (range 1–6). The response rate (CR/PR) was 14.5% (95% CI, 7.5 to 24.4), with a median progression-free survival of 4.7 months and a median overall survival of 11 months. With combination therapy, the salient grade 3/4 events were neutropenia (28%), febrile neutropenia (3.8%), hypotension (4%), hypokalemia and hypomagnesemia (5%), hypersensitivity (1%), acne-like rash (3%), peripheral neuropathy (1%), and myalgia (1%). Twenty-five patients received maintenance therapy with single-agent cetuximab (median duration of treatment was 12 weeks) and this was well tolerated. Conclusions: This large multicenter phase II study of the novel combination of cetuximab with docetaxel and carboplatin shows promising efficacy for patients with advanced and metastatic NSCLC and has an acceptable toxicity profile. No significant financial relationships to disclose.

NCT04552223: A phase II study of nivolumab plus BMS-986016 (relatlimab) in patients with metastatic uveal melanoma (UM) (CA224-094).

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. TPS9590-TPS9590
Author(s):  
Jose Lutzky ◽  
Lynn G. Feun ◽  
Norma Magallanes ◽  
Deukwoo Kwon ◽  
J. William Harbour
Keyword(s):  
T Cells ◽  
Mhc Class Ii ◽  
Uveal Melanoma ◽  
Phase Ii ◽  
Phase Ii Study ◽  
Performance Status ◽  
Objective Response ◽  
Type I ◽  
Tumor Escape ◽  
Potential Candidate

TPS9590 Background: Uveal melanoma (UM) is a rare disease but 50% of patients will eventually develop metastatic disease, for which not effective therapy is available. Liver-directed therapies, immunotherapy, targeted therapy and chemotherapy have limited activity [1]. Lymphocyte activation gene 3(LAG-3) is an immune checkpoint receptor associated with decreased T-cell effector function and tumor escape. Preclinical models have shown that dual inhibition of LAG-3 and PD-1 blockade generates synergistic anti-tumor activity [2]. Recent preclinical data indicates that uveal melanoma CD8+ T cells express the checkpoint receptor LAG3 to a greater extent than PD1 or CTLA4 [3,4]. Therefore, LAG3 is a potential candidate for checkpoint inhibitor immunotherapy in UM. Relatlimab is a human LAG-3-specific antibody isolated from immunized transgenic mice which binds to a defined epitope on LAG-3 with high affinity and specificity and potently blocks the interaction of LAG-3 with its ligand, MHC Class II. Methods: This is an open-label, single arm, single site investigator-initiated phase II study, NCT04552223. Based on Simon two-stage minimax design, 13 patients will be enrolled in Stage 1. If at least one response is noted, the study will proceed to Stage 2 and enroll an additional 14 patients. The null hypothesis will be rejected if 4 or more responses are observed among 27 patients. This design achieves 5% type I error and 80% power when the true ORR is 20%. The trial opened to accrual in December 2020. As of February 15, 2021 four patients had been enrolled the first stage of accrual. Main eligibility criteria include patients with biopsy proven metastatic uveal melanoma, previously untreated with PD-1, CTLA-4 and/or LAG-3 blocking antibodies and in good performance status. Enrolled patients are treated in the outpatient setting. Nivolumab 480 mg is mixed in the same bag with relatlimab 160 mg and administered intravenously over 60 minutes every 4 weeks until disease progression or intolerable toxicity for up to 24 months. The primary endpoint is best objective response rate (ORR). Secondary endpoints include disease control rate (DCR), progression-free survival (PFS), overall survival (OS), median duration of response (mDOR), and adverse events (AEs). Correlative studies will evaluate pre- and post-treatment characteristics of T cells in the tumor microenvironment and blood. Clinical trial information: NCT04552223.

Phase II study of binimetinib with imatinib in patients with unresectable KIT-mutant melanoma.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. TPS9594-TPS9594
Author(s):  
Katy K. Tsai ◽  
Iwei Yeh ◽  
Adil Daud ◽  
Ari Oglesby
Keyword(s):  
Phase Ii ◽  
Null Hypothesis ◽  
Response Rate ◽  
Phase Ii Study ◽  
Checkpoint Inhibitors ◽  
Objective Response ◽  
Specific Treatment ◽  
Type I ◽  
True Response ◽  
Phase Ii Studies

TPS9594 Background: Immune checkpoint inhibitors (ICI) have transformed treatment for patients (pts) with advanced melanoma, as have BRAF/MEK inhibitors for pts with BRAF V600-mutant melanoma. However, pts with acral or mucosal melanomas are in particular need of more options given a lower objective response rate (ORR) to ICI, and lower incidence of BRAF V600 driver mutation. Such BRAF mutations are found in only 5-10% of acral/mucosal melanomas, while KIT mutations/amplifications are found in 10-20%. Even when present, a KIT alteration does not guarantee response to KIT inhibition, with only about one-third responding as previously shown in 3 phase II studies. A significant number of KIT-mutant melanomas have been shown to demonstrate NF1 or SPRED1 loss, with recent preclinical work showing that such alterations are associated with the loss of negative suppression of RAS, resulting in RAS activation and MEK dependence. We hypothesize that NF1 or SPRED1 loss cooperates with KIT mutations to drive melanomagenesis and resistance to KIT inhibition, and propose to target this vulnerability with a combination approach to targeted therapy. This phase II study will be the first to evaluate the efficacy and safety of binimetinib plus imatinib in pts with KIT-mutant melanoma. Methods: This is an investigator-initiated phase II study of binimetinib in combination with imatinib in pts with BRAF V600 WT, KIT-mutant unresectable melanoma who have progressed on or who are ineligible for ICI (NCT04598009). Pts will be ≥18 yo with performance status ECOG 0-2, and have unresectable Stage IIIB/C/D or Stage IV melanoma that is BRAF V600 WT and KIT-mutant by CLIA-certified testing platform. Pts will have progressed on prior ICI or other standard-of-care (SOC) therapies, or be ineligible for or unable to tolerate SOC therapies. Pts with brain metastasis will be eligible if clinically stable and determination made that no CNS-specific treatment is required prior to study start. Pts previously treated with a MEK inhibitor will be excluded. A Simon 2-stage Minimax design will be used; the null hypothesis that the true response rate is 0.1 will be tested against a one-sided alternative. 15 pts will be accrued in the first stage. If there are £1 responses, the study will be stopped. Otherwise, 10 additional pts will be accrued for a total of 25. The null hypothesis that the true response rate is 0.1 will be rejected if ≥6 responses are observed. This yields a type I error rate of 0.05 and power of 0.8017 when the true response rate is 0.3.Primary endpoint: ORR (RECIST). Secondary endpoints: duration of response, progression-free survival, overall survival, clinical benefit rate (CR, PR, or SD ≥16 weeks), safety profile (CTCAE). Exploratory objectives to include investigations of association between clinical response and baseline NF1 and SPRED1 status, and of pathologic correlates of acquired resistance. Study began enrolling pts in December 2020 and is ongoing. Clinical trial information: NCT04598009.

Phase II Study of Weekly Nanoparticle Albumin-Bound Paclitaxel as Second- or Third-Line Therapy in Patients with Advanced Non-Small Cell Lung Cancer

Chemotherapy ◽  
2020 ◽  
Vol 65 (1-2) ◽  
pp. 21-28
Author(s):  
Mie Kotake ◽  
Tomohito Kuwako ◽  
Hisao Imai ◽  
Yoshio Tomizawa ◽  
Kyoichi Kaira ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Small Cell Lung Cancer ◽  
Phase Ii ◽  
Cell Lung Cancer ◽  
Advanced Nsclc ◽  
Phase Ii Study ◽  
Performance Status ◽  
Objective Response ◽  
Small Cell ◽  
Small Cell Lung

Introduction: Treatment outcomes in patients with advanced non-small cell lung cancer (NSCLC) are poor due to limited treatment options. Objective: We conducted a multicenter, single-arm phase II study to prospectively assess the efficacy and safety of weekly nab-PTX in patients with advanced NSCLC with failed cytotoxic chemotherapy. Methods: Patients with advanced NSCLC having adequate organ functions with a performance status of 0–1 were enrolled. A 100 mg/m2 dose of nab-paclitaxel was administered on days 1, 8, and 15 of a 28-day cycle. Primary endpoint was the objective response rate (ORR). Secondary endpoints were disease control rate (DCR), toxicity profile, progression-free survival (PFS), and overall survival (OS). Results: Between September 2013 and May 2016, 35 patients were enrolled. The ORR was 31.4%, and the DCR was 74.3%. The median PFS was 3.6 months, and the median OS was 11.4 months. The most common grade 3 or 4 toxicities included neutropenia (54.3%), leukopenia (42.9%), and anemia (11.4%). Two patients discontinued chemotherapy due to pneumonitis. Conclusions: Nab-PTX may be a later-line chemotherapeutic option for previously treated advanced NSCLC.

Sorafenib With Interferon Alfa-2b As First-Line Treatment of Advanced Renal Carcinoma: A Phase II Study of the Southwest Oncology Group

2007 ◽  
Vol 25 (22) ◽  
pp. 3296-3301 ◽  
Author(s):  
Christopher W. Ryan ◽  
Bryan H. Goldman ◽  
Primo N. Lara ◽  
Philip C. Mack ◽  
Tomasz M. Beer ◽  
...  
Keyword(s):  
Adverse Events ◽  
Phase Ii ◽  
Renal Carcinoma ◽  
Response Rate ◽  
Kinase Inhibitor ◽  
Phase Ii Study ◽  
Performance Status ◽  
Combined Treatment ◽  
Progression Free Survival ◽  
Interferon Alfa

Purpose This phase II study evaluated the activity of combined treatment with interferon alfa-2b and sorafenib, a Raf and multiple receptor tyrosine kinase inhibitor, in patients with advanced renal carcinoma. Patients and Methods Eligible patients had metastatic or unresectable renal carcinoma with a clear-cell component, no prior systemic therapy, performance status 0 to 1, and measurable disease. Treatment consisted of interferon alfa-2b 10 × 106 U subcutaneously three times weekly and sorafenib 400 mg orally bid. The primary end point was confirmed Response Evaluation Criteria in Solid Tumors response rate. Results Twelve (19%) of 62 assessable patients achieved an objective confirmed response. An additional 31 (50%) had an unconfirmed partial response or stable disease as best response. The median progression-free survival was 7 months (95% CI, 4 to 11 months). The most common adverse events were fatigue, anorexia, anemia, diarrhea, nausea, rigors/chills, leukopenia, fever, and transaminase elevation. Von Hippel-Lindau gene mutations were detected in four (22%) of 18 archival tumor specimens. Conclusion The confirmed response rate for the combination of sorafenib and interferon in advanced renal carcinoma is greater than expected with either interferon or sorafenib alone. The toxicity of this combination is dominated by adverse events common to interferon that limit further development of this regimen.

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

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

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

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