Baby-step chemotherapy as a way to deliver chemotherapy in poor PS small cell lung cancer.

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. e17500-e17500
Author(s):  
Vanita Noronha ◽  
Vijay Patil ◽  
Amit Joshi ◽  
Vamshi Muddu ◽  
Kumar Prabhash
Keyword(s):  
Low Dose ◽  
Positive Impact ◽  
Standard Dose ◽  
Performance Status ◽  
Single Agent ◽  
Median Number ◽  
Ecog Performance Status ◽  
Full Dose ◽  
Grade 3 ◽  
Low Dose Chemotherapy

e17500 Background: Majority of patients with SCLC present with advanced stage and poor ECOG performance status. Hence delivery of adequate dose of chemotherapy is compromised. We hypothesized that initial low-dose chemotherapy might improve PS and enable administration of standard-dose chemotherapy, thus extending benefit of chemotherapy to otherwise ineligible patients. Methods: 30 patients with ECOG performance status 2-4 received low-dose chemotherapy consisting of either single agent carboplatin at AUC 2 or an abbreviated course of platinum-etoposide. Patients whose PS improved got full-dose chemotherapy with the standard regimen of platinum-etoposide. Demographic details, toxicity, time to progression and overall survival were analyzed. Univariate and multivariate analysis was performed to determine factors associated with TTP and OS. Results: Median age was 58 years with male predominance. The PS was IV in 9, III in 20 and II in 1 patient. Extensive-stage and limited-stage disease was seen in 24 and 6 patients respectively.15 patients received single-agent carboplatin, 10 patients abbreviated cisplatin-etoposide, 1 patient each cyclophosphamide and cisplatin-etoposide and 3 patients refused chemotherapy. Major grade 3-4 toxicity was mucositis in 1, loose motions in 1 and hyponatremia in 4 patients. There was no grade 3- 4 haematological toxicity. The median number of dose-reduced cycles was 1 and 3 patients received more than 2 cycles. 22 patients were eligible and willing for full-dose chemotherapy. The median time to start of full-dose chemotherapy was 11.5 days (4-26 days). The median number of cycles of standard-dose chemotherapy was 5 (1-6) with 16 completing planned schedule. Grade 3-4 toxicity was neutropenia in 50%, febrile neutropenia in 25%, loose motions in 25% and hyponatremia in 40%. The overall TTP and OS was 182 days and 263 days respectively. Presence of SIADH (p = 0.02) and completion of standard treatment (p = 0.001) had a positive impact on TTP while completion of treatment (p = 0.01) and normal LDH (p = 0.03) had a positive impact on OS. Conclusions: Low-dose chemotherapy is well-tolerated and might help in extending the benefit of standard-dose chemotherapy to otherwise ineligible patients.

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]

Phase II trial of pemetrexed (P) and bevacizumab (B) in patients (pts) with recurrent or metastatic head and neck squamous cell carcinoma (HNSCC): An interim analysis

2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 6049-6049 ◽  
Author(s):  
M. V. Karamouzis ◽  
D. Friedland ◽  
R. Johnson ◽  
K. Rajasenan ◽  
B. Branstetter ◽  
...  
Keyword(s):  
Performance Status ◽  
Single Agent ◽  
Median Number ◽  
Tube Placement ◽  
Bleeding Complications ◽  
Ecog Performance Status ◽  
Curative Therapy ◽  
Highly Active ◽  
Hemorrhagic Events ◽  
Grade 3

6049 Background: P is a multi-targeted antifolate with single-agent activity in recurrent or metastatic HNSCC (RR 26%, Pivot et al. Br J Cancer 2001;85:649–55) and a preferable toxicity profile compared with cisplatin or the taxanes. B is a monoclonal antibody against the vascular endothelial growth factor that has been successfully incorporated in the treatment of other advanced solid tumors. Methods: Eligible pts had pathologically documented HNSCC, ECOG performance status 0–1, measurable disease, no history of bleeding diathesis or hemoptysis, and were not on anticoagulation. Pts had no prior systemic therapy for recurrent or metastatic HNSCC; chemotherapy as part of initial potentially curative therapy, but without P or B, was allowed if completed >6 months earlier. Treatment consisted of P 500 mg/m2 and B 15 mg/Kg, both given intravenously every 21 days, until disease progression or intolerable toxicity. All patients received folic acid, vitamin B12, and corticosteroid prophylaxis. The primary endpoint was the time to progression (TTP) with a sample size of 40 pts (one stage design) with planned interim safety analysis after the first 6 and 12 pts. Results: 14 pts have been enrolled. Median age 64 years (35–84); male/female 13/1; PS 0/1: 7/7; prior chemotherapy: 8; primary site: oropharynx (7), larynx (4), oral cavity (3). Median number of cycles 5 (1–10). With a median follow up of 5.5 months, median TTP was 6 months (95% CI, 4–8). 11 pts were evaluable for response using RECIST. Best response was CR: 2, PR: 3, SD: 6, PD: 0, with ORR 45%. There were no grade 4 toxicities in 14 evaluable pts; 2 pts had grade 3 hemorrhagic events in the first cycle (1 tumor-related and 1 due to gastric ulcer post gastrostomy tube placement), and both discontinued treatment. 3 other pts had grade 1–2 hemorrhagic events. The relationship of these events to treatment was difficult to ascertain. Other grade 3 toxicities were stomatitis, dysphagia, and fatigue (all occurred in 1 pt). Conclusions: Preliminary results show that P plus B is a novel, highly active regimen that may represent a new treatment paradigm in HNSCC. However, bleeding complications were frequent in pts with susceptibility to such events. Study accrual continues. No significant financial relationships to disclose.

scholarly journals Efficacy and Safety of Low-Dose Decitabine in Low- or Intermediate 1-Risk MDS

Blood ◽  
2018 ◽  
Vol 132 (Supplement 1) ◽  
pp. 4377-4377
Author(s):  
Zhijian Cao ◽  
Jun Ma
Keyword(s):  
Adverse Events ◽  
Median Time ◽  
Low Dose ◽  
Conflicts Of Interest ◽  
Performance Status ◽  
Median Number ◽  
Neutropenic Fever ◽  
Efficacy And Safety ◽  
Ecog Performance Status ◽  
Grade 3

Abstract OBJECTIVES: Decitabine has been approved in China for treatment with high-risk Myelodysplastic syndromes (MDS) patients (pts) in 2008. However data of decitabine on efficacy and safety of low-dose decitabine in low- or intermediate 1-risk MDS was absence. Herein,3 years datas in our centre of low- or intermediate 1-risk MDS treated with decitabine were analysed to evaluate the efficacy and safety in two subgroups. METHODS: Inclusion Criteria:Patients of age > 18; Patients with low-or intermediate 1-risk MDS. The IPSS is used to classify patients with MDS across disease subgroups. ECOG performance status ≤ 2. And normal hepatic,renal and cardiac function. Study Design: Decitabine 20mg/m2 intravenously (IV) over the course of one hour daily for 3 days. Courses were repeated every 28 days when possible. Dose reductions for grade 3 and 4 toxicities were allowed for decitabine (to 10 mg/m2 or 15 mg/m2). The primary endpoint was overall response rate (ORR). RESULTS: In total, 37 patients were enrolled and treated from September 2014 to October 2017 in our center. The median follow-up was 26 months (range, 4-49 months). The median time from diagnosis to therapy with decitabine was 3 weeks (range, 1-52 weeks). Their F/M ratio was 16/21 and the median age of the enrolled population was 58 years (range, 40-71 years). More than 70% of patients had 2 to 3 cytopenias, and 43% were transfusion dependent at enrollment. Most patients had intermediate 1-risk MDS by IPSS (n=29). Next-generation sequencing was performed in 35 patients (90%). The most frequently detected mutations included TET2 (n=15; 41%), SF3B1 (n=7; 19%), ASXL1 (n=5, 13%), RUNX1 (n= 5, 13%), and SRSF2 (n=3, 8%). The ORR after 2 cycles of decitabine was 65% (24/37),with 35% of patients (13/35) achieving a CR. Hematologic improvement was seen in 19%(7/37). The median time to best response was 3 months (range, 1-12 months). The median number of cycles received was 5 (range, 1-13 cycles). 19% of patients (7/37) became transfusion independent. The EFS and OS were 68% and 78% respectively in 1 year. The treatment was well-tolerated, with most adverse events being of grade 1 to 2, Nausea (24%), Fatigue (14%), Infection/Neutropenic fever (19%), Constipation (6%), Diarrhea (6%). Grade 3 and higher nonhematologic adverse events were rare. Grade 3 adverse events were Infection/Neutropenic fever (6%), but rare, and no grade 4 adverse events were observed. CONCLUSIONS: These data confirm that decitabine is a feasible and effective agent for low- or intermediate 1-risk MDS pts, and its need longer time to response (more than 2 cycles). Safety profile was acceptable and the most adverse events were Nausea, Fatigue, and Infection/Neutropenic fever. Disclosures No relevant conflicts of interest to declare.

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.

The Tolerability of Combination Therapy with Thalidomide and 5-Azacitidine in Patients with Advanced Myelodysplastic Syndromes (MDS).

Blood ◽  
2009 ◽  
Vol 114 (22) ◽  
pp. 1749-1749 ◽  
Author(s):  
Melita K Kenealy ◽  
John F Seymour ◽  
Cowan Linda ◽  
Alvin Milner ◽  
Pratyush Giri ◽  
...  
Keyword(s):  
Board Of Directors ◽  
Myelodysplastic Syndromes ◽  
Research Funding ◽  
Standard Dose ◽  
Performance Status ◽  
Single Agent ◽  
Median Number ◽  
Respiratory Disorder ◽  
Advisory Committees ◽  
Impaired Performance

Abstract Abstract 1749 Poster Board I-775 Introduction Both thalidomide (Thal) and 5-azacitidine (Vidaza; AZA) have single-agent activity in patients (pts) with myelodysplastic syndromes (MDS), but there is limited experience with the combination. The addition of Thal to AZA may improve efficacy, but tolerability of the combination may be limited by side-effects. Patients and Methods This analysis included all evaluable pts on the Ph I/II Australasian Leukaemia and Lymphoma group (ALLG) MDS3 study of Thal and AZA. Pts were eligible if they had any FAB subtype of MDS; those with RA and RARS also required clinically significant cytopenias. Pts were excluded if they had previously received Thal or its derivatives or any demethylating agent. All pts were treated with Thal 50mg/d for the first 28d increasing to 100mg/d for a max of 12 Mo treatment and AZA 75mg/m2/d x7d every 28d until progression or prohibitive toxicity. The protocol specified dose delays or reductions for treatment-related toxicities. Results A total of 80 pts have been enrolled, with 41 treated between 7/08 – 7/09 currently evaluable. Median age is 68.5y (42-81) with 66% male. FAB MDS category was RA 15%, RARS 10%, RAEB 46%, RAEB-t 10% and CMML 17% with IPSS low 12%, intermed-1 37%, intermed-2 34% and high 12%. Median baseline Hb 88g/L (71-127), ANC 1.91×10 9/L (0.06-87.65) and platelets 75 ×10 9/L (10-399). Median time post diagnosis was 9 Mo. Seventeen pts (41%) remain on treatment with AZA alone (n=3) or both agents (n=14) with a median follow-up of 208d (60-297d). For those still on Thal and AZA median exposure to Thal is 209d (60-297d), with a median 7 cycles of AZA (2-9). For those 27 ceased Thal median exposure was 49d (17-220d) and of 24 ceasing AZA, median number cycles was 2 (1-8). Of 27 pts ceasing one (n=3) or both (n=24) agents; 7 withdrew consent, 3 at investigator decision, 4 for toxicity, 6 progressive disease, 1 lack of efficacy, 2 death (1 respiratory failure in setting of PD and WCC>300, 1 sepsis) and 4 unknown. There were 3 additional deaths within 28d of ceasing study therapy (all with PD); 2 due to sepsis and 1 intracranial haemorrhage. No pt experienced peripheral neuropathy Gr3 or worse. During cycle 1 of the first 40 consecutive patients on treatment, there were 18 episodes of Gr3+ non-haematologic toxicity in 13 patients; this was more likely in those with ECOG 2 (67% v 26%, p=0.053), age>65y (39% v 19%, p=0.175) and baseline ANC'0.5 (75% v 21%, p=0.008). Most of these events were infection related (a recognised risk of underlying MDS and of AZA alone); others occurred on only one occasion each (syncope, postop hemorrhage, respiratory disorder, renal failure, abdominal pain, pain, thrombosis and hypokalemia). Conclusions The combination of Thal 50-100mg/d and standard dose AZA is feasible without unexpected toxicity. Infections are common in the first cycle, particularly in pts with baseline neutropenia or impaired performance status. An updated toxicity analysis will be presented. Disclosures Kenealy: Celgene Pty Ltd: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding. Seymour:Celgene Pty Ltd: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding. Mills:Celgene Pty Ltd: Honoraria, Membership on an entity's Board of Directors or advisory committees. Szer:Celgene Pty Ltd: Honoraria, Speakers Bureau.

A phase I clinical study of biweekly carboplatin and gemcitabine in patients with advanced solid tumors

2006 ◽  
Vol 24 (18_suppl) ◽  
pp. 12024-12024
Author(s):  
P. Kumar ◽  
M. Keshtgarpour ◽  
H. Kumar ◽  
A. Dudek
Keyword(s):  
Performance Status ◽  
Median Number ◽  
Maximum Tolerated Dose ◽  
Hematological Toxicity ◽  
Ecog Performance Status ◽  
Primary Tumors ◽  
Grade 3 ◽  
Number Of Cycles ◽  
Tumor Types ◽  
Dose Levels

12024 Background: Carboplatin (CBDCA) and gemcitabine (GEM) in combination is used commonly in lung cancer and is administered on a 21 day cycle. The purpose of this study was to determine the maximum tolerated dose (MTD) of CBDCA and GEM administered on a biweekly schedule and to assess safety and efficacy of this schedule. Methods: GEM was given intravenously (IV) over 30 minutes followed by CBDCA also given IV over 30 minutes. This combination was given on day 1 every 2 weeks. The dose levels examined are shown in the Table . A total of 26 patients were studied (18 male, 8 female) with median age of 56 (range 41–83 years); ECOG performance status of 24 patients were 0 (5), 1 (16), 2 (2), 3 (1); prior chemotherapy ranged from 0 to 4 regimens; median number of cycles administered per patient was 3 (range 1–9) with a total of 81 cycles. The primary tumors were lung (11), melanoma (4), head and neck (3), squamous cell penile/toe (2), bladder (2), kidney (1), gastric (1), esophageal (1) and ovary (1). Results: No DLTs were seen in any of these patients and the MTD was not reached. Delay in treatment was seen in total of 6 cycles due to myelosuppression and 1 cycle due to nausea and anorexia. Grade 3/4 hematological toxicity rates: anemia - 3/81 cycles (3.7%), neutropenia - 20/81 cycles (25%), and thrombocytopenia - 4/81 cycles (5%). Non-hematological toxicity was mild. The median time to progression was 40 days (range 4–133) and of 18 evaluable patients partial response or stable disease was seen in 7 (38.8%). Conclusions: Even at maximum tested dose of GEM at 2000 mg/m2 and CBDCA at AUC of 3.0, this schedule is well tolerated. Hematological toxicity such as neutropenia and thrombocytopenia was minimal. We plan to study this schedule of GEM and CBDCA in appropriate tumor types in combination with biologic agents. [Table: see text] [Table: see text]

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 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.

A phase II study of S-1 for previously treated small cell lung cancer (SCLC)

2009 ◽  
Vol 27 (15_suppl) ◽  
pp. e19074-e19074
Author(s):  
K. Kudo ◽  
F. Ohyanagi ◽  
A. Horiike ◽  
E. Miyauchi ◽  
I. Motokawa ◽  
...  
Keyword(s):  
Phase Ii ◽  
Response Rate ◽  
Performance Status ◽  
Single Agent ◽  
Progression Free Survival ◽  
Median Number ◽  
Ecog Performance Status ◽  
Treatment Regimens ◽  
Platinum Based Chemotherapy ◽  
Previously Treated

e19074 Background: S-1 is a novel oral 5-fluorouracil derivative that exhibits obvious activity against various tumor types including NSCLC. However, the effects of S-1 against SCLC have not been reported. The present phase II trial assesses the efficacy and safety of S-1 in previously treated SCLC patients. Methods: Eligible patients had pathologically documented SCLC that relapsed after platinum-based chemotherapy, ECOG performance status (PS) 0–2, and adequate bone marrow, kidney and liver function. Patients with untreated or symptomatic brain metastasis were excluded. Treatment comprised the oral administration of S-1 at 40 mg/m2 twice each day for 28 days every 6 weeks. The primary end point was the objective tumor response rate (RECIST). Secondary endpoints included progression-free survival and overall survival. Results: Twenty-six evaluable patients were enrolled (Simon's two-stage optimal design; α = 0.1; β = 0.1; P0 = 0.05; P1 = 0.25) with the following characteristics: male: female, 22/4; median age, 68 (33 - 79) y; PS0–1, n = 21; PS2, n = 5. The median number of prior treatment regimens was 2 (1–3). S-1 was administered for a mean of 1.3 cycles (1 - 5). One patient (3.8%) partially responded, 10 (38.5%) had stable and 15 (57.7%) had progressive disease. The overall response rate was 3.8% and the disease control rate was 42.3%. The median time to progression was 33 days. The median survival time was 8.0 months and the 1-year survival rate was 23%. This regimen was well tolerated. The common grade 3/4 toxicities included neutropenia (7.7%), leukopenia (7.7%), anemia (7.7%), hyponatremia (7.7%), rush (7.7%), infection (7.7%), and diarrhea (3.8%). None of the patients developed febrile neutropenia and no deaths were attributed to treatment. Conclusions: S-1 is well tolerated but has low activity as a single agent in previously treated patients with SCLC. No significant financial relationships to disclose.

Phase II study of pazopanib with weekly paclitaxel in refractory urothelial cancer.

2015 ◽  
Vol 33 (7_suppl) ◽  
pp. 294-294 ◽  
Author(s):  
Sandy Srinivas ◽  
Sujata Narayanan ◽  
Lauren Christine Harshman ◽  
Russell Kent Pachynski ◽  
Anthony P. Lam ◽  
...  
Keyword(s):  
Phase Ii ◽  
Phase Ii Study ◽  
Performance Status ◽  
Progression Free Survival ◽  
Median Number ◽  
Upper Urinary Tract ◽  
Weekly Paclitaxel ◽  
Moderate Activity ◽  
Ecog Performance Status ◽  
Grade 3

294 Background: Currently, there are no standard treatments for relapsed or refractory urothelial carcinoma (UC). Discouraging results have been observed in trials evaluating established chemotherapeutics as single agents or in combination regimens. Paclitaxel has moderate activity when used alone and in combination in UC. Pazopanib is active in other solid tumors secondary to its potent anti-angiogenic effects. We report the results of a multi-center phase II study evaluating the combination of paclitaxel with pazopanib in refractory UC. Methods: Eligible patients (pts) had histologically confirmed UC, with disease that progressed on upto 2 chemotherapeutic regimens. Pazopanib (800 mg) was administered daily, with weekly paclitaxel (80mg/m2) for 3 weeks in a 28 day cycle. Treatment was continued until disease progression or unacceptable toxicity. The primary endpoint of the study was response-rate (RR) based on RECISTv 1.1 criteria. Secondary endpoints included safety, and progression free-survival (PFS). Results: From April 2010 to September 2014, 32 patients were enrolled. Median age was 67 years (29-89) and median ECOG performance status was 1 (0-2). 17 pts (54%) had UC of the upper urinary tract disease and 15(47%) had primary bladder tumors. All pts had multiple metastatic sites, including 9 (28%) with liver metastases. Median number of prior cytotoxic regimens was 2, and 50% were considered cisplatin responsive. Objective responses were observed in 58% with 3 (12%) complete responses (CR), and 12 pts (46%) with partial responses (PR). Another 9 (35%) acheived stable disease (SD). High grade toxicities included grade 3 hypertension (n=2), grade 3 fatigue (n=4), grade 3 thrombosis (n=2) and grade 4 neutropenia (n=2). Nearly half of the patients( n= 14 ) required growth factor support. Conclusions: Our phase II study combining paclitaxel and pazopanib demonstratedsignificant anti-tumor activity in relapsed/refractory UC. This combination is safe, effective and is worthy of evaluation in randomized phase 3 study. Clinical trial information: NCT01108055.

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