Examining the management of muscle-invasive bladder cancer (MIBC) by medical oncologists (MO).

2012 ◽  
Vol 30 (5_suppl) ◽  
pp. 298-298 ◽  
Author(s):  
Andrea Borghese Apolo ◽  
Bernard Bochner ◽  
Seth M. Steinberg ◽  
Dean F. Bajorin ◽  
William Kevin Kelly ◽  
...  
Keyword(s):  
Bladder Cancer ◽  
Residual Disease ◽  
Performance Status ◽  
Single Agent ◽  
The United States ◽  
Perioperative Chemotherapy ◽  
Ecog Performance Status ◽  
Upper Tract ◽  
Advocacy Network ◽  
American Society

298 Background: Neoadjuvant chemotherapy (NC) for the treatment of MIBC remains underutilized in the United States despite evidence supporting its use. The aim of this project is to examine the current management of MIBC by MO to move towards standardization of practice. Methods: An electronic 26 question survey was emailed to 92 MO belonging to the Bladder Cancer Advocacy Network or the American Society of Clinical Oncology, and posted on the US Oncology portal for 8 wks. The study was approved by the Office of Management and Budget (0925-0046). Percentages are based on the fraction that responded to a given question. Results: Of the 83 respondents: 48% were non-academic. 51% were general oncologists and 45% focused on GU malignancies. The majority of MIBC referrals came from urologists (79%). Initial CT staging with abd/pelvis was required by 88%, CT chest by only 72% and PET by 21%. NC is offered by 79% of MO to all MIBC pts and by 45% to all pts with high grade upper tract urothelial carcinoma. Adjuvant chemotherapy (AC) was offered by 46% to all MIBC pts and by 41% to pts with upper tract disease. NC was not offered if ECOG performance status (PS) was >3 (49%), in T2 disease without lymphovascular invasion (29%), or with GFR of <50 ml/min (35%). Chemotherapy regimens used for NC included gemcitabine/cisplatin (90%); methotrexate/vinblastine/adriamycin/cisplatin (MVAC) (30%), dose dense MVAC (20%); gemcitabine/carboplatin (36%); single-agent gemcitabine (10%), other regimens described include carboplatin/paclitaxel and ifosfamide/doxorubicin/gemcitabine. Response to NC was assessed by CT abd/pelvis (82%), CT chest (39%), cystoscopy (30%) and PET (12%). Pts with pathologic residual disease (>pT2 or positive LN) after NC were generally observed (74%). Conclusions: The majority of MO do offer perioperative chemotherapy for MIBC pts with a trend towards increased use of NC over AC, which follows best evidence. The main reason for not offering perioperative chemotherapy was poor PS. The majority offer cisplatin-based combination therapy by preference. Increasing the rate of referrals of MIBC pts to MO, will result in more pts receiving perioperative cisplatin-based chemotherapy and may lead to better outcomes in this disease.

Phase 1 expansion trial of the LSD1 inhibitor seclidemstat (SP-2577) with and without topotecan and cyclophosphamide (TC) in patients (pts) with relapsed or refractory Ewing sarcoma (ES) and select sarcomas.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. TPS11577-TPS11577
Author(s):  
Damon R. Reed ◽  
Sant P. Chawla ◽  
Bhuvana Setty ◽  
Leo Mascarenhas ◽  
Paul A. Meyers ◽  
...  
Keyword(s):  
Phase 1 ◽  
Performance Status ◽  
Single Agent ◽  
Progression Free Survival ◽  
The United States ◽  
Primary Objective ◽  
Tumor Growth Inhibition ◽  
Ecog Performance Status

TPS11577 Background: Several sarcomas possess chromosomal translocations in FET family members ( FUS, EWSR1, and TAF15) responsible for cancer development. Sarcomas caused by FET family gene rearrangements include ES, desmoplastic round cell small tumors (DSRCT), myxoid liposarcoma (ML), and several others. Lysine specific demethylase 1 (LSD1) is a critical protein for sarcoma development and progression through its colocalization and/or association with several FET family oncogenic transcription factors. This suggests that pharmacologic inhibition of LSD1 may be a therapeutic strategy. Seclidemstat (SP-2577, Salarius Pharmaceuticals) is an oral, first-in-class, small molecule with reversible, noncompetitive inhibition of LSD1 (IC50: 25–50 nM). In vitro and in vivo data demonstrate seclidemstat, or analogs, modulate EWS/ETS transcriptional activity, down-regulating oncogene expression and up-regulating tumor-suppressor gene expression, leading to significant tumor growth inhibition in ES mouse xenograft studies. Seclidemstat has shown in in vitro ES cell lines near additivity efficacy when added to TC. In in vitro studies of other FET-translocated sarcomas, including ML (FUS/DDIT3 fusion) and clear cell sarcoma (EWS/ATF1 fusion), seclidemstat showed anti-proliferative activity. In an ongoing Phase 1 trial investigating single agent seclidemstat in advanced solid tumors (NCT03895684), three pts with metastatic FET-translocated sarcomas had a median progression-free survival of 5.7 months (range: 4.3–7.2) with a best response of stable disease despite having a median of 5 (range: 1–7) prior therapies. Methods: This dose expansion Phase 1 study (NCT03600649) assesses seclidemstat at 900 mg PO BID, the recommended Phase 2 dose, in two expansion cohorts: a single agent expansion in select sarcoma pts (n = 30) and a safety lead-in dose escalation and expansion (n = 24) of seclidemstat combined with TC in pts with ES. Pts must be ≥12 years old, have ECOG performance status of 0 or 1, with a life expectancy > 4 months. In the select sarcoma cohort, pts must have ML (n = 15) or other sarcomas with FET family translocations (n = 15) including DSRCT. One to 3 prior lines of therapy are allowed. In the ES combination cohort, up to 2 lines of prior therapy are allowed. Primary objective is safety/tolerability and secondary objective is efficacy. The trial is currently recruiting across 8 locations in the United States. Clinical trial information: NCT03600649.

Phase II study of epacadostat with pembrolizumab in metastatic or unresectable gastroesophageal junction and gastric adenocarcinoma requiring paired biopsies.

2018 ◽  
Vol 36 (4_suppl) ◽  
pp. TPS191-TPS191
Author(s):  
Adel Kardosh ◽  
Diane Tseng ◽  
Bita Sahaf ◽  
Ativ Zomet ◽  
Julia Krupa ◽  
...  
Keyword(s):  
Clinical Trial ◽  
Gastric Adenocarcinoma ◽  
Phase Ii ◽  
Response Rate ◽  
Performance Status ◽  
Gastroesophageal Junction ◽  
Single Agent ◽  
The United States ◽  
Ecog Performance Status ◽  
Major Health Problem

TPS191 Background: Gastroesophageal junction (GEJ) and gastric adenocarcinomas constitute a major health problem worldwide. Gastric cancer is the fourth most prevalent malignancy and the second leading cause of cancer death worldwide. Furthermore, the incidence of adenocarcinoma of the esophagus, GEJ and gastric cardia has risen faster than any other malignancy in the last 25 years in the United States and other Western countries. Cytotoxic chemotherapy remains the standard treatment, with progression free survival (PFS) for advanced disease of 4 to 6 months and median overall survival (OS) of 7 to 10 months. Pembrolizumab, a PD-1 inhibitor, was recently approved for advanced gastric or gastroesophageal junction adenocarcinoma whose tumors express PD-1, on the basis of a response rate of 13% seen in KEYNOTE 059 (NCT02335411). Combination immunotherapies are hypothesized to build on this response. Methods: This is a single arm, phase II clinical trial of epacadostat, a novel inhibitor of the enzyme indoleamine 2,3 dioxygenase-1 (IDO-1), in combination with pembrolizumab, in metastatic or unresectable gastroesophageal junction or gastric adenocarcinoma. A 6-month PFS of 20% with single agent pembrolizumab is the basis for the null hypothesis. We will enroll 30 patients over 18 months and follow patients for at least 6 months. This design has 80% power to reject a 20% PFS rate, if the true PFS is 39%. Eligible patients must have: adenocarcinoma of the distal esophagus, gastroesophageal junction or stomach; progression on at least one line of prior therapy for metastatic disease, and for HER2+ disease should have received prior trastuzumab; ECOG performance status 0 or 1; willing to undergo two newly-obtained biopsies - before and on-treatment, provided the procedure is not deemed high-risk and is clinically feasible. Notably, PDL-1 expression is not required. The primary endpoint is 6-month PFS, with secondary endpoints of response rate (RR), OS, and the safety and tolerability of the combination. Furthermore, comprehensive immune profiling from patient blood and tumor tissue will be performed. The study opened to accrual in September 2017 (NCT03196232). Clinical trial information: NCT03196232.

Impact of ECOG performance status on recurrent/metastatic head and neck squamous cell carcinomas treated with anti-PD1 inhibitors.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. e18004-e18004
Author(s):  
Cameron Chalker ◽  
Vicky Wu ◽  
Jenna M. Voutsinas ◽  
Victoria Hwang ◽  
Christina S Baik ◽  
...  
Keyword(s):  
Overall Survival ◽  
Clinical Outcomes ◽  
Squamous Cell ◽  
Smoking Status ◽  
Demographic Data ◽  
Performance Status ◽  
Univariate Analysis ◽  
Single Agent ◽  
Ecog Performance Status ◽  
Hpv Status

e18004 Background: Anti-PD1 checkpoint inhibitors (ICI) represent an established standard of care for patients with recurrent/metastatic head & neck squamous cell carcinoma (RMHNSCC). Landmark studies excluded patients with ECOG performance status (PS) ≥ 2; the benefit of ICI in this population is therefore unknown. Methods: We retrospectively reviewed RMHNSCC patients who received at least 1 dose of ICI at our institution. Demographic data and clinical outcomes were obtained; the latter included objective response to ICI (ORR), physician-documented CTCAE grade 2+ toxicity (irAE), and any unplanned hospitalization within 100-days of last ICI dose (UH). Associations between demographic data and clinical outcomes were explored using both uni- and multivariate analysis. Overall survival (OS) was estimated using a Cox proportional hazards model; ORR, irAE, and UH were evaluated with logistic regression. This project was approved by our institutional IRB. Results: We identified 152 RMHNSCC patients who were treated with ICI between 1/2013 and 1/2019. ECOG PS was 0 in 42 (27%), 1 in 75 (50%), 2 in 27 (18%), 3 in 2 (1%), and unknown in 6 (4%) patients. The median age was 61 (range: 25 - 90). 124 (82%) were male, 124 (82%) were white, and 69 (45%) were never-smokers. The most common primary sites were the oropharynx (n = 59, 40%), oral cavity (n = 39, 26%), nasopharynx (n = 11, 7%), and larynx (n = 10, 6%). 54 (36%) were p16+ oropharynx cancers. CPS score was available in 10 (6.6%). Single agent ICI was received by 118 (77%) patients. 66 (44%) had a documented irAE and 54 (36%) had an UH. A multivariate model for OS containing PS, smoking status and HPV status showed a strong association between inferior OS and ECOG 2/3 compared to 0/1 (p < 0.001; HR = 3.30, CI = 2.01-5.41), as well as former (vs. never) smoking status (p < 0.001; HR = 2.17, CI = 1.41-3.35). Current smoking (p = 0.25) did not reach statistical significance. On univariate analysis, poor PS was associated with inferior ORR (p = 0.03; OR = 0.25, CI = 0.06-0.77) and increased UH (p = 0.04; OR = 2.43, CI = 1.05—5.71). There was no significant association between irAE and any patient characteristic. Conclusions: We observed inferior overall survival among ICI-treated RMHNSCC patients with ECOG 2/3 in our single-institution, retrospective series. Our findings help frame discussion of therapeutic options in this poor-risk population. Further study must be done to determine which interventions are of greatest benefit for RMHNSCC patients with declining performance status.

scholarly journals Phase III Randomized, Placebo-Controlled Trial of Docetaxel With or Without Gefitinib in Recurrent or Metastatic Head and Neck Cancer: An Eastern Cooperative Oncology Group Trial

2013 ◽  
Vol 31 (11) ◽  
pp. 1405-1414 ◽  
Author(s):  
Athanassios Argiris ◽  
Musie Ghebremichael ◽  
Jill Gilbert ◽  
Ju-Whei Lee ◽  
Kamakshi Sachidanandam ◽  
...  
Keyword(s):  
Head And Neck ◽  
Disease Progression ◽  
Kinase Inhibitor ◽  
Performance Status ◽  
Single Agent ◽  
Eastern Cooperative Oncology Group ◽  
Phase Iii ◽  
Oncology Group ◽  
Ecog Performance Status ◽  
Grade 3

Purpose We hypothesized that the addition of gefitinib, an epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor, to docetaxel would enhance therapeutic efficacy in squamous cell carcinoma of the head and neck (SCCHN). Patients and Methods Patients with recurrent or metastatic SCCHN with Eastern Cooperative Oncology Group (ECOG) performance status of 2, or patients with ECOG performance status of 0 to 2 but were previously treated with chemotherapy, were randomly assigned to receive weekly docetaxel plus either placebo (arm A) or gefitinib 250 mg/d, orally (arm B) until disease progression. At the time of progression, patients in the placebo arm could receive single-agent gefitinib. EGFR, c-MET, and KRAS mutations and polymorphisms in drug metabolizing enzymes and transporters were evaluated by pyrosequencing. Results Two hundred seventy patients were enrolled before the study was closed early at interim analysis (arm A, n = 136; arm B, n = 134). Median overall survival was 6.0 months in arm A versus 7.3 months in arm B (hazard ratio, 0.93; 95% CI, 0.72 to 1.21; P = .60). An unplanned subset analysis showed that gefitinib improved survival in patients younger than 65 years (median 7.6 v 5.2 months; P = .04). Also, there was a trend for improved survival in patients with c-MET wild-type (5.7 v 3.6 months; P = .09) regardless of treatment. Grade 3/4 toxicities were comparable between the two arms except that grade 3/4 diarrhea was more common with docetaxel/gefitinib. Of 18 eligible patients who received gefitinib after disease progression in arm A, one patient had a partial response. Conclusion The addition of gefitinib to docetaxel was well tolerated but did not improve outcomes in poor prognosis but otherwise unselected patients with SCCHN.

Pemetrexed and carboplatin plus bevacizumab as first-line therapy for advanced non-squamous non-small cell lung cancer: preliminary safety results of a phase II trial

2006 ◽  
Vol 24 (18_suppl) ◽  
pp. 17111-17111
Author(s):  
J. D. Patel ◽  
T. A. Hensing ◽  
P. O’Keeffe ◽  
K. Frantonius ◽  
E. Hart ◽  
...  
Keyword(s):  
Treated Patient ◽  
Performance Status ◽  
Single Agent ◽  
Stage Iv ◽  
Patient Characteristics ◽  
Median Number ◽  
Stage Iiib ◽  
Ecog Performance Status ◽  
Minor Response ◽  
First Line Therapy

17111 Background: Bevacizumab is a novel antiangiogenic agent that has been shown to improve response rates and survival of patients with advanced non-squamous NSCLC when added to paclitaxel and carboplatin. Pemetrexed is a multitargeted antimetabolite that has shown activity in NSCLC as a single agent and when combined with carboplatin. Because the combination of pemetrexed and carboplatin has activity comparable to that of other standard platinum doublets and promising toxicity profile (Zinner, 2005), the addition of bevacizumab to this regimen is investigated. Methods: This single cohort, phase 2 study evaluates the safety and efficacy of the combination of pemetrexed and carboplatin plus bevacizumab in patients with untreated non-squamous NSCLC. Eligibility requires ECOG performance status 0–1, Stage IIIB (malignant effusion) or Stage IV non- squamous NSCLC, no evidence of CNS metastases, no anticoagulation. Treatment consists of pemetrexed 500 mg/m2 over 10 minutes, carboplatin AUC 6 over 30 minutes, and bevacizumab 15 mg/kg over 30–90 minutes. Treatment is repeated every 21 days for 6 cycles. For patients who have either stable disease or partial response, pemetrexed 500 mg/m2 and bevacizumab 15 mg/kg are continued every 21 days until progression of disease or toxicity. All patients receive folic acid, vitamin B12 and steroid prophylaxis. Tumor response is assessed using RECIST every 2 cycles during treatment with carboplatin and then every 3 cycles during treatment with pemetrexed and bevacizumab alone. Results: From 8/2005 to 12/2005, 10 (of planned 50) patients with Stage IIIB and IV non-squamous NSCLC have been enrolled and treated. Patient characteristics are: median age: 65 (48–71), 20% female, 80% male, 30% stage IIIB, 70% stage IV. Median number of cycles delivered is 5 (range 1–9). No patient has discontinued therapy secondary to progressive disease or toxicity to date. 6 patients are evaluable for response: 1 PR, 1 minor response (24% reduction), 4 SD. No grade 3/4 toxicities have been experienced. Conclusions: This is a highly tolerable and active regimen with little toxicity to date. Updated response and toxicity data will be forthcoming. Supported by Genentech Inc and Lilly Pharmaceuticals. [Table: see text]

A phase 1 study of daily oral perifosine (P) with every 3-week paclitaxel (T)

2006 ◽  
Vol 24 (18_suppl) ◽  
pp. 13134-13134 ◽  
Author(s):  
T. F. Goggins ◽  
J. J. Nemunaitis ◽  
R. Shiffman ◽  
R. Birch ◽  
D. H. Berdeaux ◽  
...  
Keyword(s):  
Dose Level ◽  
Phase 1 ◽  
Performance Status ◽  
Single Agent ◽  
State Level ◽  
Hematologic Toxicity ◽  
Ecog Performance Status ◽  
Full Dose ◽  
Phase Ii Studies ◽  
Grade 3

13134 Background: Perifosine is a novel alkylphospholipid that has been shown to affect multiple signal transduction pathways including Akt, MAPK and JNK (Kondapaka, Mol. Canc. Ther 2: 1093–1103. 2003). Treatment with a taxane initially activates Akt, and persistent activation increases resistance to the drug (Vanderweele, Mol. Canc. Ther. 3: 1605–13, 2004). Methods: Twelve patients (pts) were enrolled on this study. T was given at a dose of 175 mg/m2 on day 8 (after 7 days of perifosine) of a 21 day cycle; this was to obtain a steady state level of P at the tumor before exposure to T. The intent of the protocol was to determine if full dose P could be delivered with 50 mg of perifosine given orally 1, 2 or 3 times a day on days 1–14 of each cycle. Results: Disease sites included lung 3, thyroid 3, breast 1, esophagus 1 and other 4, Median age was 66 (range 45 - 83); 6 pts were male and median ECOG performance status was 1 (range 0–2). All pts had received prior chemotherapy (median 2 regimens); 3 had prior treatment with a taxane. Three pts were entered at each dose level and the cohort expanded to 6 pts if 2 or more pts experienced a grade 3/4 non-hematologic toxicity (DLT) during cycle 1. A dose level was toxic if 4 or more pts experienced a DLT during cycle 1. A total of 30 cycles and a median of 2 cycles (range 1–11) per patient were delivered. There were no grade 3/4 hematologic toxicities. Full dose T was given in all treatment cycles. P dose reductions were required in 6% of cycles (50 mg - 7%, 100 mg - 0%, 150 mg - 7%). One patient missed one dose due to nausea and one pt was stopped due to diarrhea. The grade 3 toxicities for each cohort are given in the table below. The elevated glucose value was 321. Nine pts were evaluable for response; two pts with thyroid cancer had stable disease by the RECIST criteria for 9 and 10+ months. Conclusions: In this study the usual single agent doses of P (150 mg daily) & T (175 mg/m2 q 3 weeks) were given together without increasing the toxicities that would be expected from using each drug alone. Phase II studies are warranted to define activity of the combination. [Table: see text] [Table: see text]

A randomized, double-blind phase II study of the oral tyrosine kinase inhibitor (TKI) axitinib (AG-013736) in combination with docetaxel (DOC) compared to DOC plus placebo (PL) in metastatic breast cancer (MBC)

2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 1003-1003 ◽  
Author(s):  
H. S. Rugo ◽  
A. Stopeck ◽  
A. A. Joy ◽  
S. Chan ◽  
S. Verma ◽  
...  
Keyword(s):  
Adverse Events ◽  
Kinase Inhibitor ◽  
Performance Status ◽  
Single Agent ◽  
Metastatic Breast ◽  
Primary Objective ◽  
Hazard Ratio ◽  
Ecog Performance Status ◽  
Double Blind ◽  
Grade 3

1003 Background: Single-agent DOC is commonly used to treat MBC. Axitinib (AG) is a potent TKI of VEGFRs. A phase I lead-in study identified 80 mg/m2 q3wks of DOC in combination with 5 mg BID of AG as the recommended phase 2 dose. The primary objective was to determine whether the time to progression (TTP) of AG+DOC arm is superior to DOC+PL. Methods: Pts with no prior chemotherapy for MBC and =12 mos from adjuvant chemotherapy (aCT), measurable disease, ECOG performance status (PS) of 0–2, and no uncontrolled brain metastases were randomly assigned (2:1) to receive treatment with either DOC+AG or DOC+PL without prophylactic growth factor in cycle 1. Tumor measurements were performed q9wks. Pts were stratified according to estrogen receptor (ER) status, prior aCT and PS (0–1 or 2). Results: A total of 168 pts were randomized. 92 pts had received prior aCT, 27 of whom received a prior taxane. Treatment arms were well balanced for prior adjuvant and taxane therapy. A median of 7 cycles of AG+DOC (range: 1–18) and 7 cycles of DOC+PL (range: 1–23) were administered. The most common non-hematologic adverse events observed in the AG+DOC arm included diarrhea (60%), nausea (53%), alopecia (51%), fatigue (49%), stomatitis (44%) and vomiting (40%). Grade 3/4 adverse events that were increased with AG+DOC vs DOC included febrile neutropenia (16 vs 7%), fatigue (13 vs 5%), stomatitis (13 vs 2%), diarrhea (11 vs 0%) and hypertension (5 vs 2%). Other grade 3/4 hematologic toxicities were similar in both arms. The median TTP (by RECIST) was 8.2 mo with AG+DOC arm and 7 mo with DOC+PL arm with a hazard ratio of 0.73 (prespecified, one-sided p=0.052). The overall response rate (ORR) was 40% for AG+DOC arm and 23% for DOC+PL arm (p=0.038). In a hypothesis-generating subgroup analysis, the median TTP in patients receiving prior aCT was 9.0 mo with AG+DOC arm and 6.3 mo with DOC+PL arm with a hazard ratio of 0.54 (p=0.012). Within this stratum, ORR was 45% for AG+DOC arm and 13% for DOC+PL arm (p=0.003). Conclusions: The anti-angiogenic TKI AG combined with DOC (80 mg/m2 q3wks) as first line therapy for MBC has an acceptable safety profile and promising anti-tumor activity. No significant financial relationships to disclose.

Phase II single institution study of sequential biochemotherapy (BCT) for patients (pts) with stage IV melanoma (M)

2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 8580-8580
Author(s):  
P. R. Bojanapally ◽  
D. T. Alexandrescu ◽  
V. Rusciano ◽  
P. H. Wiernik ◽  
J. P. Dutcher
Keyword(s):  
Median Survival ◽  
Phase Ii ◽  
Performance Status ◽  
Single Agent ◽  
Stage Iv ◽  
Experimental Therapy ◽  
Ecog Performance Status ◽  
Maximum Benefit ◽  
Prospective Phase ◽  
Metastatic Sites

8580 Background: The utility of BCT for M remains controversial. A prospective phase II study was conducted to assess the clinical benefit of BCT in patients with stage IV M. Methods: Between March 2005 and March 2006 11 pts (6 Male and 5 Female with a median age of 54 (range 36 - 82)) with metastatic M were treated with paclitaxel 225 mg/m2 via continuous 24 hour IV infusion every 3 wks for 4 cycles or maximum benefit followed by HD IL2, 1.33 mg/m2 every 8 hours for 5 days of wk1 and wk3 based on pts tolerance to a maximum of 12 doses per wk. 2 Male pts received IL2 followed by paclitaxel. Pts had a ECOG performance status of 0 - 2, with a median time of 60 months since diagnosis of disease (range 7 to 240 months). 11 pts (92%) had multiple metastatic sites (50% had lung mets, 58% had liver mets) and 4 pts (33%) had prior chemotherapy or immunotherapy. Results: Of the 13 assessable pts one achieved a PR after paclitaxel and CR after IL2 continuing at 20+ months. One had SD for 1 year after receiving HD IL2 and SD for 6 months while on paclitaxel independently, One had PR for 6 months on paclitaxel and one had MR with paclitaxel for 3 months. 9 pts (69%) had PD on paclitaxel and again on IL2, with a median survival from treatment of 7 months, 2 of these got no IL2 due to rapid PD. An overall response rate of 30% (1 CR on paclitaxel + IL2 , 1 PR on paclitaxel, 2 SD (including MR) on paclitaxel) was seen with a median survival from treatment of 15 months. Conclusions: In this study there may be prolonged survival among responders, which may be due to synergy of sequential BCT, or may reflect single agent activity of each drug. BCT should still be considered as an experimental therapy and further evaluated. No significant financial relationships to disclose.

Phase I/II study of the combination of sorafenib and temsirolimus in patients with metastatic melanoma

2009 ◽  
Vol 27 (15_suppl) ◽  
pp. 9026-9026 ◽  
Author(s):  
K. B. Kim ◽  
M. A. Davies ◽  
N. E. Papadopoulos ◽  
A. Y. Bedikian ◽  
W. Hwu ◽  
...  
Keyword(s):  
Phase I ◽  
Performance Status ◽  
Single Agent ◽  
Stage Iv ◽  
Pharmacokinetic Data ◽  
Advanced Cancer Patients ◽  
Ecog Performance Status ◽  
Multikinase Inhibitor ◽  
Taste Alteration

9026 Background: Inhibition of Signal transduction pathways at multiple levels may be a more effective therapeutic cancer strategy for advanced cancer patients. Sorafenib, a multikinase inhibitor and temsirolimus, an inhibitor of critical survival pathways, are targeted compounds with single agent anti-tumor activity in several solid tumors. Inhibition of mutant B-Raf and the AKT signaling pathway has been effective in vitro with melanoma cell lines. Therefore, we designed a phase I/II study of the combination of sorafenib and temsirolimus to inhibit multiple pathways for greater clinical efficacy.Methods: Patients (pts) with stage IV or unresectable or recurrent stage III melanoma and ECOG performance status of 0 to 1 were eligible. Pts with treated brain metastases were eligible if they had not progressed for 3 months. Sorafenib was given orally twice daily and temsirolimus was given intravenously once a week, both starting on day 1, with a 4-week cycle. Responses were assessed every 2 cycles per RECIST. Results: To date, 22 pts have been enrolled and treated. Median age was 56.5, and 17 were male. Median ECOG PS was 1. The MTD doses were sorafenib 400 mg in AM / 200 mg in PM daily and temsirolimus 25 mg IV weekly. The dose-limiting toxicity (DLT) included thrombocytopenia, hand-foot syndrome (HFS), serum transaminase elevation and hypertriglyceridemia. Other common adverse events were dry skin, fatigue, taste alteration, anorexia, flatulence, diarrhea, skin rash, insomnia, neuropathy, myalgia, and headaches, anemia, hypercholesterolemia, hyperglycemia and hypophosphatemia. There were 9 pts with stable disease among 21 evaluable pts for response. Conclusions: Sorafenib and temsirolimus can be administered concomitantly although with significant toxicity at higher dose levels. Currently, pts are enrolled in a dose expansion cohort. Pharmacokinetic data will be presented. Supported in part by NCI grant UO1 CA062461 and N01 CM17003. [Table: see text] No significant financial relationships to disclose.

Phase II study of RAD001 (everolimus) in previously treated small cell lung cancer (SCLC)

2009 ◽  
Vol 27 (15_suppl) ◽  
pp. 8107-8107 ◽  
Author(s):  
A. P. Kotsakis ◽  
A. Tarhini ◽  
D. Petro ◽  
R. Flaugh ◽  
G. Vallabhaneni ◽  
...  
Keyword(s):  
Disease Control ◽  
Signaling Pathway ◽  
Performance Status ◽  
Single Agent ◽  
Oral Intake ◽  
Progression Free Survival ◽  
Akt Signaling ◽  
Akt Signaling Pathway ◽  
Ecog Performance Status ◽  
Prior Chemotherapy

8107 Background: Everolimus (E) is an oral inhibitor of mammalian target of rapamycin (mTOR), a novel target for anti-cancer therapy that plays a central role in the PI3K/AKT signaling pathway and other pathways that mediate tumor growth, proliferation, and angiogenesis. E has shown preclinical activity in SCLC cell lines and xenograft models. Methods: Eligibility included SCLC with disease progression after up to 2 prior chemotherapy regimens, ECOG performance status (PS) 0–2, and adequate bone marrow, liver, and kidney function. Patients (pts) were treated with E 10 mg, orally, once daily. Primary endpoint was the disease control rate (DCR), i.e. complete response (CR), partial response (PR) and stable disease (SD), after 2 cycles of E (6 weeks) in pts who received at least 1 cycle. A 2-stage design was followed. PI3K/AKT signaling pathway molecular biomarkers (AKT, pAKT, PTEN, P-S6, p-4E- BP1) will be evaluated on baseline tumor tissue. Results: 40 pts were enrolled; 14 males/26 females; median age 64 years (44–80); PS 0: 17, PS 1: 23; prior chemotherapy status: 1 prior regimen/sensitive relapse (i.e. relapse >60 days from completion of first-line chemotherapy): 23 pts; 1 prior regimen/refractory: 4 pts; 2 prior regimens: 13 pts. 28 pts (70%) received ≥ 2 cycles of E, 7 (18%) 1 cycle and 5 (12%) did not complete the first cycle of E due to adverse events or early progression. Best response in 35 evaluable patients: 1 (3%) PR, 8 (23%) SD and 26 (74%) progression; DCR at 6 weeks was 26% with a duration of disease control of 2.7–6.3 months; median progression-free survival 1.4 months; and median overall survival 5.5 months. No grade 4 toxicity was seen. Grade 3 toxicities included thrombocytopenia (2), neutropenia (2), infection (1), pneumonitis (1), fatigue (1), elevated transaminases (1), hyperglycemia (1), diarrhea (1), and acute renal failure due to dehydration from diarrhea and poor oral intake (1). Conclusions: E is well tolerated but has limited single-agent antitumor activity in unselected patients with pretreated SCLC. [Table: see text]

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