Phase II trial of imatinib mesylate (I) in combination with docetaxel (D) in the treatment of patients (pts) with recurrent or persistent epithelial ovarian carcinoma (EOC)

2009 ◽  
Vol 27 (15_suppl) ◽  
pp. e16552-e16552
Author(s):  
L. Usha ◽  
M. L. Larson ◽  
N. Kazmi ◽  
T. O'Brien ◽  
L. A. Winkelman ◽  
...  
Keyword(s):  
Disease Progression ◽  
Cancer Progression ◽  
Tumor Response ◽  
Kinase Inhibitor ◽  
Performance Status ◽  
Single Agent ◽  
Chemotherapeutic Agents ◽  
Hematological Toxicity ◽  
Platinum Compound ◽  
Grade 3

e16552 Background: D has a known single-agent activity in advanced EOC with the response rate of at least 10%. I is a multi-targeted tyrosine kinase inhibitor shown in preclinical studies to decrease interstitial pressure in the tumor and facilitate influx of chemotherapeutic agents into the tumor. Methods: A single-institution trial was conducted in pts with advanced EOC in 2005–2007. The primary endpoint of the study was to determine a tumor response to the study combination. Pts were required to have received 1 or 2 prior chemotherapeutic regimens including a platinum compound and have performance status 0–2. Pts were to receive D 60 mg/m2 IV every 3 weeks and I 400 mg/day by mouth continuously. Planned target accrual for the first stage of the study was 15 pts with the preset minimum of 3 responses to proceed to the second stage. Tumor response was evaluated by RECIST criteria after every 3 cycles of D. Treatment was continued until disease progression or unacceptable toxicity. Results: Study was terminated early due to lack of response and significant toxicities. A total of 10 pts were enrolled. The age range of the pts was 55–79 with the mean age = 64. Five pts were evaluable for response and in all of them, cancer progression was observed after 3 cycles of combination therapy (0 responses). Five pts were taken off the study after 1 cycle of treatment either due to serious adverse events (SAEs) or disease progression. Among grade 3 and 4 SAE's observed in the study were 4 cases of hematological toxicity, 1 case of rash, 1 case of dizziness, and 1 case of deep venous thrombosis. The median progression-free survival for pts on the study was 7.5 weeks. Conclusions: Although the sample size of this study was small, the combination of I and D at the above doses appears ineffective in the population of moderately-pretreated women with advanced EOC. The majority of grade 3 and 4 SAE's were due to myelosuppression likely caused by D rather than I. No significant financial relationships to disclose.

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.

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 pilot study of apatinib reversing paclitaxel resistance in heavily pretreated advanced gastric cancer (AGC).

2017 ◽  
Vol 35 (4_suppl) ◽  
pp. 89-89
Author(s):  
Rongbo Lin ◽  
Shen Zhao ◽  
Hui Li ◽  
Jie Liu ◽  
Nanfeng Fan
Keyword(s):  
Disease Progression ◽  
Promising Result ◽  
Performance Status ◽  
Early Death ◽  
Progression Free Survival ◽  
Chemotherapeutic Agents ◽  
Paclitaxel Resistance ◽  
Heavily Pretreated ◽  
Grade 3

89 Background: In vitro or vivo, apatinib can reverse ABC-mediated multidrug resistance not only by inhibiting their transport function, but also by downregulating ABC expression. Methods: The patients with advanced gastric adenocarcinoma were resistant to paclitaxel-containing regimen (disease progression during or within 3 months after chemotherapy) and had measurable lesions received apatinib 850 mg, po, qd combined with paclitaxel alone (80 mg/m2 d1, d8, and d15, repeated 4-weekly) or POF (reported in 2007, 2008, 2009, 2010 ASCO, paclitaxel 135 mg/m2, oxaliplatin 85 mg/m2, and leucovorin 400 mg/m2, d1; 5-FU 2400 mg/m2 for 46h, repeat 2-weekly). The choice of regimen was left to clinician discretion in term of performance status and whether the agent that will be given has been resistant. Results: From 14th August 2015 to 1st March 2016, seven patients were eligible. The median age was 49 years (range, 43 to 67 years), 5 were males and 2 were females. The prior chemotherapeutic agents were summarized in table. Four patients had disease progression during apatinib. Two PRs, four SDs (unconfirmed), and one early death were observed. At a median follow-up of 238 days, the median progression-free survival was 124 days, the median survival was 194 days (range, 33 to 398+ days). Grade 3 to 4 neutropenia, anaemia, hypertension, fatigue, stomatitis was one patient respectively. No treatment-related death occurred. Conclusions: This study showed promising result that apatinib reverses paclitaxel resistance in heavily pretreated AGC. Clinical trial information: NCT02697838. [Table: see text]

Final results of a phase II study of erlotinib, docetaxel and cisplatin in patients with recurrent/metastatic head and neck cancer

2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 6013-6013 ◽  
Author(s):  
E. S. Kim ◽  
M. S. Kies ◽  
B. S. Glisson ◽  
A. Tsao ◽  
L. E. Ginsberg ◽  
...  
Keyword(s):  
Growth Factor ◽  
Head And Neck ◽  
Response Rate ◽  
Kinase Inhibitor ◽  
Performance Status ◽  
Treatment Options ◽  
Single Agent ◽  
Progression Free Survival ◽  
Egfr Signaling Pathway ◽  
Grade 3

6013 Background: Interrupting the epidermal growth factor receptor (EGFR) signaling pathway has shown promise in a variety of cancers and preclinical data has demonstrated possible synergy with platinums and taxanes. Treatment options for recurrent/metastatic HNSCC are limited. A study of cisplatin and docetaxel showed a response rate of 40% and 9.6 month median survival. Erlotinib, an EGFR tyrosine kinase inhibitor, had a 4.3% response rate as single agent in HNSCC. Because of the possible synergy and efficacy, we proposed to study the combination of cisplatin, docetaxel and erlotinib in advanced HNSCC. Methods: Patients (pts) were required to have adequate performance status, measurable disease, no prior EGFR therapy, and may have received prior induction, concomitant or adjuvant chemotherapy, but not for recurrent/metastatic disease. Sites of disease included squamous cell head and neck sites excluding nasopharynx and sinus. Treatment included docetaxel 75 mg/m2 and cisplatin 75 mg/m2 intravenously every 3 weeks and erlotinib 150 mg by mouth daily. All agents were started on day 1. Pts were treated with growth factor support. Results: The trial has completed accrual to 50 pts. 47 pts are available for analysis at this time. Median age is 56 years (range 39–72). ECOG PS is 0, 1, 2 (6, 29, 2 pts). 43 pts are evaluable for efficacy. All responses were confirmed via RECIST. Complete responses have been in observed in 4 pts, partial responses in 25 pts and 12 pts have stable disease for an overall response rate of 67% and disease control rate of 95%. After a follow-up of 19 months, median overall survival was 11 months (8.61, 22.5, 95% CI) and progression free survival was 6.01 months (4.37, 8.25). 6 pts had grade 3/4 febrile neutropenia, 4 pts had grade 3/4 dehydration, 3 pts had grade 3 diarrhea, and 2 pts had grade 3/4 GI bleeding. The most common grade 1–2 toxicities were diarrhea, nausea, and rash. Conclusions: The combination of cisplatin, docetaxel and erlotinib is well tolerated and has very encouraging activity in recurrent/metastatic HNSCC. Tissues are being collected and analyzed for correlative markers including downstream EGFR pathway markers (p-akt, mek, k-ras). Final efficacy and biomarker results will be presented at the annual meeting. No significant financial relationships to disclose.

A phase I study of dovitinib (TKI258) in Japanese patients with advanced solid tumors.

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. 3088-3088
Author(s):  
Hiroya Takiuchi ◽  
Masahiro Gotoh ◽  
Motoki Yoshida ◽  
Takayuki Kii ◽  
Keishi Yamashita ◽  
...  
Keyword(s):  
Phase I ◽  
Disease Progression ◽  
Solid Tumors ◽  
Phase I Study ◽  
Kinase Inhibitor ◽  
Performance Status ◽  
Dose Range ◽  
Japanese Patients ◽  
Advanced Solid Tumors ◽  
Grade 3

3088^ Background: Dovitinib is a tyrosine kinase inhibitor with demonstrated inhibitory activity against FGFRs, VEGFRs, and PDGFRs in vivo. Based on responses observed in renal cell carcinoma, breast cancer, AML, melanoma, and multiple myeloma in clinical studies in the West, we investigated dovitinib in Japanese patients (pts). Methods: This multicenter phase I study determined the maximum tolerated dose (MTD) of dovitinib based on the occurrence of dose-limiting toxicity (DLT) in Japanese pts with advanced solid tumors. Following a 2-day pharmacokinetic (PK) run-in period, dovitinib was administered orally once daily on a 5-days-on/2-days-off schedule in 28-day cycles until disease progression or withdrawal. The planned dose range was 100-600 mg/day. A 2-parameter Bayesian logistic regression model based on the principle of escalation with overdose control was used to estimate the MTD. Results: In total, 28 pts received dovitinib: 100 mg (n = 3), 200 mg (n = 3), 300 mg (n = 7), 400 mg (n = 9), and 500 mg (n = 6). The median age was 58.5 years (range, 30-76); 16 of 28 pts (57%) were male. All pts had stage IV disease, with an ECOG performance status of 0 or 1. Pts completed a median of 3 cycles. One pt is currently ongoing in the study (peritoneal adenocarcinoma, 400-mg cohort, cycle 19), 23 discontinued due to disease progression, and 4 discontinued due to adverse events (AEs). All DLTs were grade 3: anorexia (n = 1; 300 mg), nausea/vomiting (n = 1; 400 mg), liver function disorder (n = 1; 400 mg), and increased alanine transaminase (n = 1; 500 mg). The most common grade 3/4 AEs (occurring in >10% of pts) suspected to be related to study drug were lymphopenia (18%), neutropenia (14%), abnormal hepatic function (14%), decreased white blood cell count (14%), decreased appetite (14%), and hypertension (14%). Best responses were confirmed partial response in 1 pt (4%; peritoneal adenocarcinoma, 400-mg cohort), stable disease in 9 pts (32%), and progressive disease in 10 pts (36%). No treatment-related deaths have been reported. Safety and PK parameters were comparable to those of non-Japanese pts in the global study. Conclusions: The study has completed enrollment. Dovitinib was found to be tolerable at doses up to 500 mg, which was declared as the MTD in Japanese pts.

Oxaliplatin as Single Agent or in Combination in Chronic Lymphocytic Leukaemia (CLL).

Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 4982-4982
Author(s):  
Marco Montillo ◽  
Sara Miqueleiz ◽  
Alessandra Tedeschi ◽  
Francesca Ricci ◽  
Alfredo Molteni ◽  
...  
Keyword(s):  
Disease Progression ◽  
Excision Repair ◽  
Single Agent ◽  
Tumor Lysis Syndrome ◽  
Platinum Compound ◽  
Bulky Disease ◽  
Major Toxicity ◽  
Cross Links ◽  
Binet Stage ◽  
Grade 3

Abstract Patients who failed fludarabine (FLU) or showing a relapse after several lines of chemo or immuno therapy have poor chance to obtain further response to treatment. Oxaliplatin (OX) is a third generation platinum compound with a 1,2 diaminocyclohexamine carrier ligand, it has a different activity and side effect profile from cisplatin. In order to test the activity of OX in CLL we administered first this agent as monotherapy in relapsed patients. OX covalently binds DNA, inducing DNA intra and inter-strand cross-links. FLU has been shown to have a biochemical modulating effect on others antineoplastic agents. Moreover, FLU and Ara-C act synergistically to inhibit excision repair of DNA cross-links. This evidence provides a rationale to test the combination of OX, FLU and Ara-C in patients with advanced CLL. The first cohort of patients received OX 140 mg/m2, as single agent. The second cohort of patients received OX, at increasing dose 17.5 (1st course), 25 (2nd course), 35 mg/m2 (from 3rd course up to the 6th course), days 1–4; Fludarabine 25 mg/m2, days 2 and 3; Ara-C 1 g/m2, days 2 and 3. Courses were given every 4 weeks for a total of 6 courses; all patients received G-CSF 5μcg/m2. Prophylaxis against tumor lysis syndrome, PCP and DNA virus were provided. Seven patients (M=4;F=3; Median age = 62 years; Binet stage B =3, Binet stage C= 4) who received a median of 3 previous (range 2–5) lines of treatment, two of them resistant to FLU, have been treated with OX as single agent. Patients receiving at least 1 course were evaluable for toxicity. Four patients completed the entire program of treatment, 2 patients received 4 courses of OX and they didn’t continued treatment because of persistant neutropenia from the previous course. The last patient stopped OX after the second course because of disease progression. The major toxicity was hematologic. Grade 3–4 neutropenia and thrombocytopenia were experienced in 5 and 6 patients respectively. There were no treatment related deaths. One patient showed a disease progression, 2 patients showed PR while 4 remained with stable disease. No response was observed in patients who had failed FLU. In the second cohort 4 patients (M=3: F=1; Median age=61 years) have been treated with the combination of FLU, OX and Ara-C. Three patients presented abdominal bulky disease resistant to the last treatment. Three patients were FLU resistant. Three patients received the entire program while the fourth patient stopped treatment after three courses because of a hepatic toxicity while on partial response. The major toxicity was hematologic and appeared OX-dose dependent. Grade 3/4 neutropenia was experienced by 1/4, 2/4 and 4/4 patients treated at 17.5, 25 and 35 mg/m2 OX levels respectively. Grade 3–4 thrombocytopenia was experienced by 2/4, 3/4 and 4/4 patients treated at 17.5, 25 and 35 mg/m2 OX levels respectively. No treatment related deaths were observed. One patient reached CR, and 3 patients a PR. Considering the three patients with bulky disease, disappearance of the abdominal involvement in one patient and reduction > 50% in the other two patients were recorded. The usefulness of OX given as single agent is limited in patients with advanced CLL, at the contrary these preliminary results of the combination OX, FLU and Ara-C appeared very promising. Further accrual of patients to be treated with the combination using OX at 35 mg/m2, days 1–4, is warranted.

Fulvestrant (F) plus sorafenib (S) as salvage therapy for hormone receptor positive (HR+) metastatic breast cancer (MBC) failing prior aromatase inhibitor (AI) treatment.

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. e11042-e11042
Author(s):  
Kristine H. Lethert ◽  
Deirdre J. Nauman ◽  
Yolanda Prado ◽  
Mark Seligman ◽  
Kasra Karamlou ◽  
...  
Keyword(s):  
Growth Factor ◽  
Disease Progression ◽  
Kinase Inhibitor ◽  
Single Agent ◽  
Growth Factor Receptor ◽  
Metastatic Breast ◽  
Median Number ◽  
Toxicity Assessment ◽  
Vegf Inhibitor ◽  
Grade 3

e11042 Background: Upon MBC progression with AI treatment; F, an estrogen receptor (ER) antagonist, is often used. Furthermore, vascular endothelial growth factor (VEGF) remains a potential target in MBC. S is a multi-kinase inhibitor of VEGF, Raf, platelet-derived growth factor receptor beta, Flt-3, and c-KIT. Prior studies of S show activity with chemotherapy and as a single agent. Combination therapy with an anti-estrogen and a VEGF inhibitor may be more effective than either agent alone. This pilot study combines F + S for HR+ MBC. Methods: Upon disease progression with an AI, 8 pts were treated with F. Concurrent S was administered starting day 1 until disease progression or unacceptable toxicity. Assessment of tumor status with computed tomography and/or bone scan was performed at baseline and every 2 cycles until disease progression. Results: Median age = 58; 75 % <65. ER and PR + = 6 pts; ER + and PR - = 2 pts. 6 pts were treated with adjuvant chemotherapy and endocrine therapy, with subsequent AI for MBC. 2 pts were metastatic at presentation and treated with prior AI. Median number of days on treatment = 220; median number of cycles = 7. 75% had grade 2/3 HFS; 50% required S dose modification. However, HFS and rash/desquamation were the only grade 3 toxicities (3 pts) with no additional grade 3/4 toxicities or dose modifications for other toxicities. Other grade 2 toxicities: neutropenia, myalgias, arthralgias, fatigue, pruritis. Only 1 pt discontinued the study at investigator’s decision for grade 3 HFS. There were no deaths on study. The remaining 7 pts continued F + S until disease progression with stable disease over a range of 2 to 22 cycles. Median time to progression was 7.3 months. Conclusions: Upon progression with an AI, treatment with F + S may provide advantage for some HR+ MBC pts beyond treatment with F alone. Future studies involving S in MBC should focus on identifying the population that will benefit the most in exchange for toxicities associated with S. [Table: see text]

Phase II Study of Dasatinib In Patients with Relapsed Chronic Lymphocytic Leukemia.

Blood ◽  
2010 ◽  
Vol 116 (21) ◽  
pp. 4488-4488 ◽  
Author(s):  
Ali M Al-Ameri ◽  
Xavier Badoux ◽  
Alessandra Ferrajoli ◽  
William G. Wierda ◽  
Luis Fayad ◽  
...  
Keyword(s):  
Phase Ii ◽  
Kinase Inhibitor ◽  
Phase Ii Study ◽  
Performance Status ◽  
Objective Response ◽  
Lymphocytic Leukemia ◽  
Hematological Toxicity ◽  
Abl Kinase ◽  
Grade 3

Abstract Abstract 4488 Src-family kinases (SFK) are described to be over expressed in CLL resulting in increased BCR signaling. Aberrant activation of the SFK, Lyn, leads to defective apoptosis of CLL cells in-vitro. C-Abl kinase is also overexpressed in CLL cells compared to normal B-lymphocytes. Since dasatinib is a dual Src and c-abl kinase inhibitor with in-vitro pro-apoptotic properties in CLL cells, we investigated the activity of dasatinib in patients (pts) with CLL. We designed a phase II study of dasatinib in pts with relapsed CLL/SLL and T-PLL. Pts were eligible if they were previously treated and had indication for therapy according to NCI-working group criteria. All pts had adequate performance status, renal and liver function prior to therapy. Treatment consisted of dasatinib 50mg given orally twice daily. In case of suboptimal response the dose of dasatinib could be increased up to a maximum dose of 70mg twice daily. Dose reductions to 20mg twice daily were permitted for toxicity. Pts were assessed for treatment response according to 1996 NCI-WG criteria. Seventeen pts have been enrolled in this study. The median age was 67 years (42-83 years), 9 (52%) had Rai stage III-IV, median beta-2 microglobulin levels was 5.9 (3.0 – 11.8) mg/L. The median number of prior treatments was 4 (1 – 8). An objective response (PR) was observed in 1 patient, 13 pts had no objective response and 3 pts were not evaluable for response due to early discontinuation of therapy (0-3 days). Fourteen pts remained on therapy for a median of 2 (0-19) months with 4 pts discontinuing due to disease progression and 9 pts discontinuing due to adverse events and lack of response. Hematological toxicities consisted of grade 3–4 neutropenia in 76% of the pts, grade 3–4 thrombocytopenia in 44% of pts and grade 1–2 anemia in 80%. Non-hematological toxicity consisted of grade 3–4 fatigue in 1 patient and grade 3 pleural effusions in another patient. Grade 1 and 2, toxicities included flushing 38%, headache 38%, fatigue 46% anorexia and nausea 46%, and diarrhea 23%. Several pts showed evidence of biological activity. Treatment with dasatinib lacks efficacy in pts with heavily pretreated CLL. Responses occurred in only 6% of pts and dasatinib administration was associated with a high incidence of neutropenia. Disclosures: O'Brien: Bristol-Myers Squibb: Research Funding.

Interim safety analysis of the randomized phase III PELICAN trial evaluating pegylated liposomal doxorubicin (PLD) versus capecitabine as first-line therapy for metastatic breast cancer

2009 ◽  
Vol 27 (15_suppl) ◽  
pp. 1118-1118
Author(s):  
S. Al-Batran ◽  
S. Saupe ◽  
M. Schmidt ◽  
R. Kreienberg ◽  
B. Otremba ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Metastatic Breast Cancer ◽  
Disease Progression ◽  
Performance Status ◽  
Single Agent ◽  
Metastatic Breast ◽  
Pegylated Liposomal Doxorubicin ◽  
Phase Iii ◽  
First Line ◽  
Grade 3

1118 Background: Treatment of metastatic breast cancer (MBC) focuses on relieving symptoms and extending life. Single-agent therapy is preferred in the first-line setting to reduce the risk of toxicity and maintain quality of life. The PELICAN trial was designed to evaluate efficacy and safety of first-line PLD vs capecitabine at standard approved dosages. Methods: PELICAN is an open-label, multinational, randomized, multicenter trial. MBC Patients (pts) were randomized to receive PLD (50 mg/m2 every 28 days) or capecitabine (1250 mg/m2 BID x 14 days every 21 days) until disease progression or unacceptable toxicity. The primary endpoint was to compare time to disease progression between treatment arms. Toxicity was evaluated continuously. Results: The study is still ongoing, but no longer recruiting. So far, 210 pts (PLD, 105; capecitabine, 105) were evaluated for safety, of whom 131 pts have already completed their treatment (83 for disease progression, 19 for toxicity, 5 died, 24 for other reasons). 90% of pts had ECOG performance status 1 or 2, and 79% were postmenopausal. Mean age was 61.5 years, and 34% received prior adjuvant anthracycline. Pts received a median of 4 cycles of PLD and a median of 5 cycles of capecitabine. Over 90% of pts in both groups experienced at least one adverse event (AE). Grade 3/4 AEs were reported in 99 patients (PLD, 44; capecitabine, 55). Hand foot syndrome (HFS) was the most common AE (grade 3: PLD 35%; capecitabine 19%), followed by diarrhea (grade 3/4: PLD, 0; capecitabine, 13%) and thromboembolic events (PLD, 0%; capecitabine, 9%). Other grade 3/4 AEs affected 1 week in 16%. Conclusions: Overall, first-line monotherapy with PLD or capecitabine at approved doses was maintainable for a median of about 4 months with manageable AEs. Interim safety results of the PELICAN trial show no unanticipated toxicity. Efficacy results will be available once all patients have completed their therapy. [Table: see text]

scholarly journals Phase 2 study of the JAK kinase inhibitor ruxolitinib in patients with refractory leukemias, including postmyeloproliferative neoplasm acute myeloid leukemia

Blood ◽  
2012 ◽  
Vol 119 (20) ◽  
pp. 4614-4618 ◽  
Author(s):  
Alireza Eghtedar ◽  
Srdan Verstovsek ◽  
Zeev Estrov ◽  
Jan Burger ◽  
Jorge Cortes ◽  
...  
Keyword(s):  
Acute Myeloid Leukemia ◽  
Myeloid Leukemia ◽  
Kinase Inhibitor ◽  
Performance Status ◽  
Single Agent ◽  
Median Number ◽  
Phase 2 ◽  
Phase 2 Study ◽  
Grade 3 ◽  
Acute Myeloid

Abstract We conducted a phase 2 study of ruxolitinib in patients with relapsed/refractory leukemias. Patients with acceptable performance status (0-2), adequate organ function, and no active infection, received ruxolitinib 25 mg orally twice a day for 4 weeks (1 cycle). Response was assessed after every 2 cycles of treatment, and patients who completed 2 cycles were allowed to continue treatment until disease progression. Dose escalation to 50 mg twice daily was permitted in patients demonstrating a benefit. Thirty-eight patients, with a median age of 69 years (range, 45-88), were treated. The median number of prior therapies was 2 (range, 1-6). Twelve patients had JAK2V617F mutation. Patients received a median of 2 cycles of therapy (range, 1-22). Three of 18 patients with postmyeloproliferative neoplasm (MPN) acute myeloid leukemia (AML) showed a significant response; 2 achieved complete remission (CR) and one achieved a CR with insufficient recovery of blood counts (CRi). The responding patients with palpable spleens also had significant reductions in spleen size. Overall, ruxolitinib was very well tolerated with only 4 patients having grade 3 or higher toxicity. Ruxolitinib has modest antileukemic activity as a single agent, particularly in patients with post-MPN AML. The study was registered at www.clinicaltrials.gov as NCT00674479.

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