Correlation of hypertension and proteinuria with outcomes in elderly bevacizumab (BEV)-treated patients with metastatic colorectal cancer (mCRC): Analysis of the BECOX and BECA studies.

2013 ◽  
Vol 31 (15_suppl) ◽  
pp. 3589-3589
Author(s):  
Antonieta Salud Salvia ◽  
Jaime Feliu ◽  
Maria Jose Safont ◽  
Carlos García-Girón ◽  
Jorge Aparicio ◽  
...  
Keyword(s):  
Odds Ratio ◽  
Older Patients ◽  
Overall Response Rate ◽  
Response Rate ◽  
Female Gender ◽  
Time To Progression ◽  
Factors Associated ◽  
Primary Endpoints ◽  
Ecog Ps ◽  
Clinical Trial Information

3589 Background: Studies suggest a relationship between hypertension, which is common in older patients, and outcome in BEV-treated patients with mCRC. We performed a retrospective analysis of two studies – BECA [Feliu et al BJC 2010; EudraCT 2005-002808-42] and BECOX [NCT01067053] – to determine if hypertension and proteinuria predict outcome in elderly BEV-treated patients. Methods: Patients ≥70 years received capecitabine 1250 mg/m2 bid po on days 1–14 + BEV 7.5 mg/kg on day 1 every 21 days in the BECA study; BECOX patients received capecitabine 1000 mg/m2 bid po on days 1–14 with BEV 7.5 mg/kg and oxaliplatin 130 mg/m2 on day 1 (oxaliplatin discontinued after cycle 6). Primary endpoints were overall response rate (ORR) in BECA and time to progression (TTP) in BECOX. Correlations were investigated for hypertension and proteinuria with ORR, disease control rate (DCR), overall survival (OS) and TTP. Logistic regression was performed to identify factors associated with hypertension and proteinuria. Results: 127 patients were included (BECA n=59; BECOX n=68; 61% male, median age 76 years; ECOG PS 0/1/2 45%/52%/2%). During the study 16% of patients had hypertension and 61% had proteinuria as an adverse event. Hypertension correlated with DCR, OS and TTP but not ORR; proteinuria correlated with ORR and DCR (Table). Development of proteinuria or hypertension in the first 2 cycles did not correlate with efficacy. Risk factors associated with development of hypertension were female gender (odds ratio [OR] 0.241; p=0.011) and greater no. of BEV cycles (OR 1.112; p=0.002); factors associated with proteinuria were diabetes (OR 3.869; p=0.006) and greater no. of BEV cycles (OR 1.181; p<0.0001). Conclusions: This analysis of the BECOX and BECA studies suggests that hypertension and proteinuria are associated with outcome in BEV-treated elderly patients with mCRC. Clinical trial information: NCT01067053. [Table: see text]

Lenalidomide plus dexamethasone is more effective than dexamethasone alone in patients with relapsed or refractory multiple myeloma regardless of prior thalidomide exposure

Blood ◽  
2008 ◽  
Vol 112 (12) ◽  
pp. 4445-4451 ◽  
Author(s):  
Michael Wang ◽  
Meletios A. Dimopoulos ◽  
Christine Chen ◽  
M. Teresa Cibeira ◽  
Michel Attal ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Overall Response Rate ◽  
Response Rate ◽  
Progression Free Survival ◽  
Efficacy And Safety ◽  
Time To Progression ◽  
Free Survival ◽  
Refractory Multiple Myeloma ◽  
Previously Treated ◽  
Survival Studies

AbstractThis analysis assessed the efficacy and safety of lenalidomide + dexamethasone in patients with relapsed or refractory multiple myeloma (MM) previously treated with thalidomide. Of 704 patients, 39% were thalidomide exposed. Thalidomide-exposed patients had more prior lines of therapy and longer duration of myeloma than thalidomide-naive patients. Lenalidomide + dexamethasone led to higher overall response rate (ORR), longer time to progression (TTP), and progression-free survival (PFS) versus placebo + dexamethasone despite prior thalidomide exposure. Among lenalidomide + dexamethasone-treated patients, ORR was higher in thalidomide-naive versus thalidomide-exposed patients (P = .04), with longer median TTP (P = .04) and PFS (P = .02). Likewise for dexamethasone alone-treated patients (P = .03 for ORR, P = .03 for TTP, P = .06 for PFS). Prior thalidomide did not affect survival in lenalidomide + dexamethasone-treated patients (36.1 vs 33.3 months, P > .05). Thalidomide-naive and thalidomide-exposed patients had similar toxicities. Lenalidomide + dexamethasone resulted in higher rates of venous thromboembolism, myelosuppression, and infections versus placebo + dexamethasone, independent of prior thalidomide exposure. Lenalido-mide + dexamethasone was superior to placebo + dexamethasone, independent of prior thalidomide exposure. Although prior thalidomide may have contributed to inferior TTP and PFS compared with thalidomide-naive patients, these parameters remained superior compared with placebo + dexamethasone; similar benefits compared with placebo + dexamethasone were not evident for thalidomide-exposed patients in terms of overall survival. Studies were registered at http://www.clinicaltrials.gov under NCT00056160 and NCT00424047.

Hope and Prognostic Disclosure

2007 ◽  
Vol 25 (35) ◽  
pp. 5636-5642 ◽  
Author(s):  
Jennifer W. Mack ◽  
Joanne Wolfe ◽  
E. Francis Cook ◽  
Holcombe E. Grier ◽  
Paul D. Cleary ◽  
...  
Keyword(s):  
Odds Ratio ◽  
Overall Response Rate ◽  
Response Rate ◽  
First Year ◽  
Physician Communication ◽  
Multivariable Model ◽  
Prognostic Information ◽  
Dana Farber Cancer Institute ◽  
The Relationship ◽  
Parental Recall

Purpose Physicians sometimes selectively convey prognostic information to support patients’ hopes. However, the relationship between prognostic disclosure and hope is not known. Patients and Methods We surveyed 194 parents of children with cancer (overall response rate, 70%) in their first year of treatment at the Dana-Farber Cancer Institute and Children's Hospital (Boston, MA), and we surveyed the children's physicians. We evaluated relationships between parental recall of prognostic disclosure by the physician and possible outcomes, including hope, trust, and emotional distress. Our main outcome was assessed by asking parents how often the way the child's oncologist communicated with them about the children's cancers made them feel hopeful. Results Nearly half of parents reported that physician communication always made them feel hopeful. Parents who reported receiving a greater number of elements of prognostic disclosure were more likely to report communication-related hope (odds ratio [OR], 1.77 per element of disclosure; P = .001), even when the likelihood of a cure was low (OR, 5.98 per element of disclosure with likelihood of a cure < 25%; P = .03). In a multivariable model, parents were more likely to report that physician communication always made them feel hopeful when they also reported receipt of more elements of prognostic disclosure (OR, 1.60; P = .03) and high-quality communication (OR, 6.58; P < .0001). Communication-related hope was inversely associated with the child's likelihood of cure (OR, 0.65; P = .005). Conclusion Although physicians sometimes limit prognostic information to preserve hope, we found no evidence that prognostic disclosure makes parents less hopeful. Instead, disclosure of prognosis by the physician can support hope, even when the prognosis is poor.

A Phase I/II Trial of Bortezomib, Low Dose Intravenous Melphalan and Dexamethasone for Patients with Relapsed Multiple Myeloma.

Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 3542-3542 ◽  
Author(s):  
Rakesh Popat ◽  
Catherine Williams ◽  
Mark Cook ◽  
Charles Craddock ◽  
Supratik Basu ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Phase I ◽  
Median Time ◽  
Low Dose ◽  
Overall Response Rate ◽  
Response Rate ◽  
Chemotherapeutic Agents ◽  
Time To Progression ◽  
Overall Response ◽  
Grade 3

Abstract Background: Bortezomib is an effective treatment for patients with relapsed multiple myeloma with an overall response rate (MR+PR+CR) of 46% and time to progression of 6.2 months (APEX study). We and others have previously demonstrated potent in-vitro synergy with chemotherapeutic agents such as melphalan and it is likely that this will translate into improved responses in the clinical setting. Methods: This was a multi-centre, non-randomised Phase I/II clinical trial for patients with relapsed multiple myeloma. Bortezomib 1.3mg/m2 was given on Days 1,4,8 and 11 of a 28 day cycle, and intravenous melphalan on Day 2 for a maximum of 8 cycles. In the Phase I component melphalan was given at 2.5, 5,7.5 and 10mg/m2 in a dose escalation scheme and the maximum tolerated dose (MTD) of 7.5mg/m2 was taken forward to an expanded Phase II component. Dexamethasone 20mg on the day of and the day after each dose of bortezomib was permitted for progressive or stable disease after 2 or 4 cycles respectively. Responses were classified by EBMT criteria. Results: To date 39 patients have been enrolled (median age 61years [range 40–77]) with a median of 3 lines of prior therapy [range 1–5] of which 26 (67%) have had one previous autologous stem cell procedure and 4 (10%) have had two. 23 (59%) have had prior exposure to thalidomide and 4 (10%) to bortezomib. 36 have now completed at least 1 cycle and are therefore evaluable for response. The overall response rate (CR+PR+MR) across all treatment levels was 75% rising to 81% (CR 11%; nCR 3%; VGPR 8%; PR 39%; MR 19%) with the addition of dexamethasone in 13 cases for suboptimal response. Rapid responses were seen with the median time to response being 1 month [range 1–6]. The median time to progression is 10.1 months and the median overall survival has not yet been reached at a median follow-up of 7.4 months. Of the patients that have had disease progression 7 (35%) had responses of longer duration than their previous therapy. The MTD was defined by unacceptable delays in administering treatment due to myelosuppresion. The toxicities have been acceptable with 13 SAEs reported of which 8 were hospitalisation due to infection. The most common grade 3–4 adverse events were: thrombocytopenia (53%), infections (25%), neutropenia (17%) and neuropathy (17%). Three grade 3 cardiac events were seen (myocardial infarction, atrial fibrillation and cardiac failure) and GCSF was administered to 13 patients as treatment and prophylaxis of grade 4 neutropenia. 13 patients were withdrawn from the study due to toxicity of which 7 were for neuropathy and 3 for delayed haematological recovery. Of note, 11 patients (28%) had pre-existing grade 1 neuropathy prior to starting therapy. Summary: The combination of bortezomib, low dose intravenous melphalan and dexamethasone appears to be highly effective in patients with relapsed multiple myeloma where a response rate of 81% is seen with 14% achieving nCR/CR. The toxicity profile associated is predictable, manageable and predominantly haematological. Recruitment is ongoing to a total of 53 patients.

Bortezomib, Low Dose Intravenous Melphalan and Dexamethasone for Patients with Relapsed Multiple Myeloma: Final Results of a Phase I/II Clinical Trial.

Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 2713-2713
Author(s):  
Rakesh Popat ◽  
Catherine Williams ◽  
Mark Cook ◽  
Charles Craddock ◽  
Supratik Basu ◽  
...  
Keyword(s):  
Clinical Trial ◽  
Multiple Myeloma ◽  
Phase I ◽  
Median Time ◽  
Low Dose ◽  
Overall Response Rate ◽  
Response Rate ◽  
Time To Progression ◽  
Overall Response ◽  
Grade 3

Abstract Background: Bortezomib is an effective treatment for patients with relapsed multiple myeloma with an overall response rate (≥PR) of 43% and time to progression of 6.2 months (APEX study). We and others have previously demonstrated potent in-vitro synergy with chemotherapeutic agents such as melphalan and it is likely that this will translate into improved responses in the clinical setting. Methods: This was a multi-centre, non-randomised Phase I/II clinical trial for patients with relapsed multiple myeloma. Bortezomib 1.3mg/m2 was given on Days 1,4,8 and 11 of a 28 day cycle, and intravenous melphalan on Day 2 for a maximum of 8 cycles. In the Phase I component melphalan was given at 2.5, 5,7.5 and 10mg/m2 in a dose escalation scheme and the maximum tolerated dose (MTD) of 7.5mg/m2 was taken forward to an expanded Phase II component. Dexamethasone 20mg on the day of and the day after each dose of bortezomib was permitted for progressive or stable disease after 2 or 4 cycles respectively. Responses were defined by EBMT criteria. Results: 53 patients were enrolled (median age 61years [range 40–77]) with a median of 3 lines of prior therapy [range 1–5] of which 26 (67%) have had one previous autologous stem cell procedure and 4 (10%) have had two. 23 (59%) have had prior exposure to thalidomide and 4 (10%) to bortezomib. The overall response rate (≥PR) across all treatment levels (n=52) was 65% rising to 69% (CR 19%; nCR 4%; VGPR 6%; PR 40%; MR 15%) with the addition of dexamethasone in 27 cases for suboptimal response. Of the 32 patients treated at the MTD the overall response rate (≥PR) was 78% (CR 28%; nCR 6%; VGPR 6%; PR 38%; MR 9%). Rapid responses were seen with the median time to response being 1 month [range 1–6]. The median time to progression was 10 months and the median overall survival has not yet been reached at a median follow-up of 17 months. Of the patients that have had disease progression 7 (35%) had responses of longer duration than their previous therapy. The MTD was defined by unacceptable delays in administering treatment due to myelosuppresion. The toxicities have been acceptable with 13 SAEs reported of which 8 were hospitalisation due to infection. The most common grade 3–4 adverse events were: thrombocytopenia (53%), infections (25%), neutropenia (17%) and neuropathy (17%). Three grade 3 cardiac events were seen (myocardial infarction, atrial fibrillation and cardiac failure) and GCSF was administered to 13 patients as treatment and prophylaxis of grade 4 neutropenia. 19 patients were withdrawn from the study due to toxicity of which 7 were for neuropathy and 3 for delayed haematological recovery. Of note, 11 patients (28%) had pre-existing grade 1 neuropathy prior to starting therapy. Summary: The combination of bortezomib, low dose intravenous melphalan and dexamethasone appears to be highly effective in patients with relapsed multiple myeloma with a response rate (≥PR) at the MTD of 78% including 34% nCR/CR. The toxicity profile is predominantly haematological.

Favorable Outcome In Patients with Poor Prognosis Acute Myeloid Leukemia (AML) Using a 2-Day Induction Regimen Incorporating High Dose Cytarabine and Mitoxantrone.

Blood ◽  
2010 ◽  
Vol 116 (21) ◽  
pp. 1069-1069
Author(s):  
Melissa L Larson ◽  
Sheena Sahota ◽  
Margaret C Keller ◽  
Bharathi Muthusamy ◽  
Allison Zindell ◽  
...  
Keyword(s):  
Mortality Rate ◽  
Induction Therapy ◽  
Older Patients ◽  
Overall Response Rate ◽  
Response Rate ◽  
Remission Induction ◽  
High Dose ◽  
Younger Patients ◽  
Induction Regimen ◽  
High Dose Cytarabine

Abstract Abstract 1069 Background: Cytogenetic data plays an important role in assessing prognosis and determining choice of therapy for AML. Traditionally, patients with AML are treated with infusional cytarabine and an anthracycline. CR rates with this regimen have been reported at 50–60%. Evaluation of novel treatment regimens for AML should include determination of the impact of the regimen on intermediate and unfavorable cytogenetics. We present a retrospective analysis of a 2-day remission induction regimen, based on the concept of timed sequential therapy. The regimen combines high dose cytarabine, which has been shown to improve remission rates when used in induction therapy, and dose intensified anthracycline therapy, which has been shown to improve outcome in younger patients. The cycling cells are eradicated during an initial pulse of therapy, then, previously quiescent cells are targeted during the second pulse of therapy. Here we present the analysis of the study regimen and the response rates of patients with intermediate and unfavorable cytogenetic profiles. Patients and Methods: One hundred fifty five patients categorized as having intermediate or unfavorable cytogenetics were treated with timed sequential chemotherapy from 1998–2009. The treatment regimen consisted of two doses of cytarabine 2 gm/m2 IVPB given over 3 hours, administered 12 hours apart. This was followed by one dose of mitoxantrone 30 mg/m2 IVPB over 1 hour on days 1 and 5. Pre-therapy cytogenetic data was collected for each patient. Responses to therapy were determined based on IWG response criteria for AML. Results: One hundred fifty five patients with intermediate and unfavorable karyotypes received high dose cytarabine and mitoxantrone for remission induction therapy. Median age of patients was 55 years (ranged from 17–85). Sixty patients were 60 years or older. Eighty three patients (53.5%) had intermediate and 72 (46.5%) had unfavorable karyotypes. The younger patients (under 60 years of age) with intermediate cytogenetics achieved the following responses: 34 CR, 6 CRi, and 2 CRp. The overall response rate (ORR) was 80.8% for these younger patients, while the ORR for the older patients (over 60 years of age) with intermediate cytogenetics was 77.4% (15 CR, 4 CRi, 5 CRp). In the unfavorable cytogenetic category, the ORR of the younger patients (under 60 years of age) was 60.5% with 13CR, 8 CRi, and 5 CRp, while an ORR of 44.8% was shown in the older patients (over 60 years of age) with 9 CR, 1 CRi, and 3 CRp. Overall, twenty two out of seventy two (30.5%) had CR in the unfavorable group, 9 (12.5%) had CRi, and 8 (11%) had CRp for an overall response rate of 54%. The 30 day mortality rate was 3.8% (6/155). The 60 day mortality rate was 11.6%. The most common adverse events were Grade 3/4 hematologic toxicities. Conclusion: This convenient, 2-day induction regimen leads to high response rates with low treatment-related mortality in older patients and patients with unfavorable cytogenetic characteristics. Based on the tolerability and effectiveness, this regimen could potentially be useful in high risk transplant-eligible patients for remission induction. It appears that this regimen would also be appropriate for initial cytoreduction in elderly patients with AML prior to introduction of novel therapeutic strategies, such as hypomethylating agents or oral clofarabine for consolidation and maintenance. Disclosures: No relevant conflicts of interest to declare.

Randomized, multicenter, crossover phase II trial to compare exemestane (E) vs. anastrozole (A) in postmenopausal patients (pt) with advanced breast cancer (ABC) and positive hormone receptors (HR). Final efficacy analysis of GEICAM 2001–03 study

2006 ◽  
Vol 24 (18_suppl) ◽  
pp. 638-638 ◽  
Author(s):  
J. Mayordomo ◽  
A. Llombart ◽  
M. Martín ◽  
A. Antón ◽  
A. Barnadas ◽  
...  
Keyword(s):  
Hormone Receptors ◽  
Overall Response Rate ◽  
Response Rate ◽  
Phase Ii Trial ◽  
Stage Iv ◽  
Time To Progression ◽  
Efficacy Analysis ◽  
Crossover Phase ◽  
Frequent Site ◽  
Α And Β Errors

638 Background: Head-to-head comparison of a steroidal aromatase inhibitor (AI) (E) vs. a non-steroidal AI (A) with crossover at the time of progression to evaluate the sequence of administration. Principal and secondary objectives were overall response rate (ORR), clinical benefit (CB) and time to progression (TTP). Methods: Postmenopausal pt with measurable ABC and positive HR, were stratified [previous tamoxifen (tam) (yes vs. no), previous chemotherapy (ct) (yes vs. no) and stage (IIIb vs. IV)], and randomized to E (25mg/day), or A (1mg/day) until progression. As per Simon’s test, with a p1 of 25% ORR and a p0 of 10% ORR, α and β errors 0.05 and 10%, 50 pt per arm were needed. Results: 103 (51 vs. 52) pt were recruited between 2002 and 2004. Main pt characteristics: median age 70 and 73 years, 82 vs. 88% stage IV, 12 vs. 17% previous ct, 51 vs. 50% previous tam, median size of lesions of 5 vs. 4 cm, mean number of lesions of 1.4 in both arms. Most frequent site of lesions were breast (33 vs. 35%), lymph nodes (22% vs. 25%) and connective tissue (27% vs. 23%). Efficacy: For initial treatment ORR was 37% (CI95% 24–51) in arm E vs. 52% (CI95% 38–66) in arm A (p= 0.151). 47% of pt in E vs. 60% in A presented CB (p=0.202). Mean TTP for arm E was 8.1 months (m) (1.1–15.2) and for arm A was 12.1 m (6.6–17.6) (p=0.4716). 11 pt (arm E) and 12 (arm A) crossed-over after progression. Following crossover mean TTP for E was 4.4 m (3.7–5.1) and for second line A was 1.9 m (0.1–3.7) (p=0.0172). Conclusions: E and A seem to be equivalent in terms of efficacy as first treatment for postmenopausal pt with ABC and positive HR. We suggest a possible advantage of the steroidal AI, exemestane, following disease progression on the non-steroid AI anastrozole. [Table: see text]

Prospective phase II trial of a combination of gemcitabine, cisplatin and UFT as first-line treatment in patients with advanced, unresectable, non-small cell lung carcinoma

2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 18109-18109
Author(s):  
S. S. Jin ◽  
Y. Min ◽  
H. Kim ◽  
J. Ahn ◽  
Y. Jegal ◽  
...  
Keyword(s):  
Survival Time ◽  
Overall Response Rate ◽  
Advanced Nsclc ◽  
Response Rate ◽  
Performance Status ◽  
Small Cell ◽  
Time To Progression ◽  
Small Cell Lung ◽  
First Line ◽  
Grade 3

18109 Background: Most patients with advanced non-small cell lung cancer (NSCLC) receive either single agents or doublet chemotherapy. For non-elderly patients in good performance status, platinum-based double combinations represent the standard treatment. And oral UFT had the survival advantage in adjuvant setting. Therefore we performed a phase II study using the combination of gemcitabine, cisplatin and UFT as a first line therapy in patients with advanced NSCLC. Methods: Eligible patients had histologically or cytologically confirmed stage IIIB or IV NSCLC with good performance status and were chemotherapy-naive. This study was two-stage design and planned number of patients was forty-seven. Gemcitabine (1,250 mg/m2, 10 mg/kg/min on days 1 and 8) and cisplatin (75 mg/m2 on day 1) were injected intravenously and UFT (400 mg/day) was administered orally on day 1–14. Treatment repeated every 3 weeks. Primary end point was overall response rate and secondary end points were overall survival, time to progression and toxicity. Results: Thirty seven patients with advanced NSCLC were enrolled. The median age of the patients was 60 years (range: 44 to 72). The performance status (WHO) was 0 in 4, 1 in 30 and 2 in 3 patients. Twenty three patients completed six cycles. Complete response was achieved in 1 (3%) patient, partial response in 22 (59%) patients, stable disease in 9 (24%) patients. Overall response rate was 62% on intent to treat basis. Among patients who response evaluation was possible (33 patients), response rate was 70%. The median survival time was 14.5 months (95% CI 6.9, 22.3) and the 1 year survival was 35% and then median time to progression was 3.4 months(95% CI 3, 3.9). Toxicities were moderate and mostly hematological adverse events. Grade 3/4 neutropenia occurred in 37%, 5 patients with febrile neutropenia. Grade 3/4 anemia and thrombocypenia was occurred in 37% and 5%. Nonhematologic toxicities were mild. Conclusion: The combination therapy consisted of gemcitabine, cisplatin and UFT is active and well tolerable first line regimen for NSCLC patients. No significant financial relationships to disclose.

Oxaliplatin plus paclitaxel for recurrent and metastatic cervical cancer (CC): New York Cancer Consortium Trial P5840

2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 5549-5549 ◽  
Author(s):  
D. Y. Kuo ◽  
S. V. Blank ◽  
B. Kobrinsky ◽  
P. Christos ◽  
T. A. Caputo ◽  
...  
Keyword(s):  
Cervical Cancer ◽  
New York ◽  
Confidence Interval ◽  
Overall Response Rate ◽  
Response Rate ◽  
Phase Ii Trial ◽  
Hematologic Toxicity ◽  
Time To Progression ◽  
Prior Chemotherapy ◽  
Experienced Grade

5549 Background: Although cisplatin (cis) is an effective radiosensitizer, its activity in patients (pts) with advanced and recurrent CC is disappointing. Oxaliplatin (O) might exhibit greater activity and be suitable for combination with paclitaxel (P). Methods: Pts with advanced and recurrent CC who had not received prior chemotherapy except radiosensitizing cis were treated with P 175 mg/m2 IV and O 130 mg/m2 IV every 21 d. Response (R), as determined by RECIST criteria and confirmed at 9 weeks (wk), and toxicity were primary outcomes. If R in = 8 patients (pts) of 18, accrual to 46 could ensue. Results: Of 17 pts enrolled, 16 were treated. Histology: 7 adeno/10 squamous.The median age was 57 (range 33–78) and 13 had had prior radiation (10 with cis). Median cycles: 3 (0–8). One CR and 4 PRs were achieved for an overall response rate of 29% (95% confidence interval: 10.3%, 56.0%). Additionally, 4 had stable disease, but this was not confirmed at 15wk. Time to progression in those responding was 21 wk (range 11–51). 7 pts are alive. 6 pts experienced grade (gr) 3/4 hematologic toxicity. Neuropathy occurred following cycle 3 in 2 pts (gr3). Additonal gr 3/4 toxicities were gastrointestinal (GI)/metabolic in 6, thrombotic in 1 and hypersensitivity in 1. There were no treatment-related deaths. Conclusions: In the stage I of our Phase II trial, O and P demonstrate a 29% response rate when used to treat advanced and recurrent CC. Toxicities of this regimen are hematologic, gastrointestinal, and neurologic. Supported by N01-CM-62204. No significant financial relationships to disclose.

A safety and schedule seeking trial of Bcl-2 inhibitor obatoclax in previously untreated older patients with acute myeloid leukemia (AML)

2009 ◽  
Vol 27 (15_suppl) ◽  
pp. 3579-3579
Author(s):  
A. Raza ◽  
N. Galili ◽  
G. Borthakur ◽  
T. H. Carter ◽  
D. F. Claxton ◽  
...  
Keyword(s):  
Older Patients ◽  
Myeloid Leukemia ◽  
Response Rate ◽  
Single Agent ◽  
Hepatic Function ◽  
Eligibility Criteria ◽  
Molecule Inhibitor ◽  
Infusion Schedule ◽  
Ecog Ps ◽  
To Receive

3579 Background: Obatoclax (Ob) is a small-molecule inhibitor of all Bcl-2 prosurvival proteins. In a previous study a 70 year old patient with untreated AML had a cytogenetic CR 8 days after receiving 20 mg/m2 of Ob over 24 hrs. This study evaluated the single-agent response rate in older patients with previously untreated AML. Methods: A Safety phase to evaluate escalating doses of Ob given by 3-hr infusion was performed. Based on previous results, the dose of 60 mg over 24 hrs was used for the 24-hr infusion arm of the Schedule Seeking phase, in which Ob was administered as either a 3-hr or 24-hr infusion for 3 consecutive days every 2 wks. The endpoint of the Schedule Seeking phase was CR after C2 in 16 randomized patients. Eligibility criteria included age ≥ 70, untreated AML (1 prior Rx allowed in Safety phase), ECOG PS ≤2, adequate renal and hepatic function. PK samples were collected during C1. Results: 18 patients (8 male; median age 82) were enrolled. 2/3 patients enrolled into the 1st cohort (30 mg x 3 days) of the Safety phase had DLT events (ataxia and somnolence). 3 patients enrolled into a 20 mg x 3 days cohort had no DLTs; this dose was used for Schedule Seeking patients receiving 3-hr infusions. In the Schedule Seeking phase, 7 patients were randomized to receive 20 mg by 3-hr infusion and 5 were randomized to receive 60 mg by 24-hr infusion. The most common (>25%) AEs were euphoric mood (50%), ataxia (38%), & somnolence (38%). Efficacy data after C2 show that 3 patients in the 20 mg 3-hr infusion cohort in the Safety phase and 1 at the same dose & schedule in the Schedule Seeking phase had ≥50% decrease in BM blasts after C2, which was not seen in the 60 mg 24-hr infusion cohort. There were no CRs. There was a single death by D28 (24-hr infusion). There were significant differences in PK by infusion schedule. Conclusions: MTD for Ob as a 3-hr infusion administered in older patients with AML on 3 consecutive days is 20 mg/day, and both this regimen and 60 mg as a 24-hr infusion x 3 days were well tolerated. Evidence of biological activity was seen with the 3-hr infusion schedule but not with the 24-hr infusion schedule, suggesting that efficacy may be improved with the 3-hr infusion schedule and may be related to PK differences. [Table: see text]

First-line cisplatin (P) with docetaxel (TXT) or vinorelbine (VNR) in patients with advanced non-small cell lung cancer: A randomized phase II trial of the Gruppo Oncologico Italia Meridionale

2009 ◽  
Vol 27 (15_suppl) ◽  
pp. e19042-e19042
Author(s):  
V. Gebbia ◽  
D. Galetta ◽  
V. Lorusso ◽  
M. Caruso ◽  
F. Riccardi ◽  
...  
Keyword(s):  
Advanced Nsclc ◽  
Response Rate ◽  
Phase Ii Trial ◽  
Stage Iv ◽  
Hematological Toxicity ◽  
First Line ◽  
Primary Endpoints ◽  
Randomized Phase Ii ◽  
P 75 ◽  
Ecog Ps

e19042 Background: P-based doublets are considered standard therapy for advanced NSCLC. The GOIM consider P/VNR as a reference treatment. P/TXT doublet has been reported to be active but it's not well known its real impact on QoL in comparison to P/VNR. Methods: Pts received either 6 courses of P/TXT or P/VNR with QoL and safety being the primary endpoints. Secondary endpoint included response rate, TTP, OS, and tolerability. Patients with stage IV/IIIB, age ≤70, and ECOG PS 0–1, were eligible. Sample size was calculated according to Fleming's single-stage procedure. QoL was analysed using the EORTC questionnaire, responses and toxicity according to the RECIST and NCI-CTC criteria. Pts were randomized to: TXT 75 mg/m2 over 60 min followed by P 75 mg/m2 on d1 every 21 d, or VNR 30 mg/m2 on d 1,8 and P 80 mg/m2 on d1 every 21 d. Results: From 12/06 to 3/08 86 pts were enrolled: P/TXT 42pts, M/F 32/10, IIIB/IV 8/34, squamous/not-squamous:13/29, median age 61 (r 41–70); P/VNR 44 pts, M/F 35/9, IIIB/IV 10/33, squamous/not-squamous 14/30, median age 62 (r 44/70). No statistically significant differences were observed in QoL among the two arms. Detailed analysis of side-effects showed no difference among the two regimens with the exception of G3–4 neutropenia and leukopenia with were slightly higher in the P/VNR arm (p=0.02 and p=0.0005 respectively). The use of G- CSF/darbopoietin was more frequent in pts treated with P/VNR than in the P/TXT arm (p=0019). Conclusions: Final data show an equivalence among the two arms regarding QoL and activity but with a slightly more hematological toxicity in the P/VNR arm. Both regimens are to be considered as standards in the treated of advanced NSCLC. [Table: see text]

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