Pegylated liposomal doxorubicin (PLD) with bevacizumab (B) in second-line treatment of ovarian cancer (OC): Pharmacokinetics (PK), safety, and preliminary outcome results

2009 ◽  
Vol 27 (15_suppl) ◽  
pp. 5548-5548
Author(s):  
F. M. Muggia ◽  
L. Boyd ◽  
L. Liebes ◽  
A. Downey ◽  
C. Muller ◽  
...  
Keyword(s):  
Primary Endpoint ◽  
Pegylated Liposomal Doxorubicin ◽  
Progression Free Survival ◽  
Disease Status ◽  
Left Ventricular ◽  
Uncontrolled Hypertension ◽  
Left Ventricular Ejection ◽  
Parameter Estimates ◽  
Ventricular Ejection Fraction ◽  
Grade 3

5548 Background: PLD activity in platinum-resistant OC is modest. B, with its activity in platinum(Plat)-sensitive and Plat-resistant patients (pts), has not been combined with PLD. PLD intratumoral concentrations, if affected by B, might be reflected in PLD PK. This phase II study of PLD + B was started in 2007 to accrue 48 pts, unless 4 serious (> grade 3) adverse events (AEs) supervened. Methods: Improvement in progression-free survival (PFS) at 6 m from 25 to 40% at 6 m in Plat-resistant OC is primary endpoint. PK of PLD alone at 1h, d 7 and d 21 (cycle 1) vs with B (cycle 2), safety, and response rates (RECIST and CA125 criteria) were secondary endpoints. Dosing: PLD 30 mg/m2 followed by B 15 mg/kg on cycles 2–7 (with option to continue) d 1 every 3 w. Pts recurring within 6 m of platinum-based treatment for OC after < 3 prior regimens (but no PLD or B) were eligible. Exclusions: bowel obstruction, prior perforation, uncontrolled hypertension, or vascular disease. Hematologic, mucocutaneous and renal toxicities were evaluated prior to each cycle, MUGA scans every third cycle; disease status by CA125 and/or RECIST every third cycle. Results: 21 of 24 pts enrolled to date are evaluable. Median age is 65, range 52–83; most had 2 prior chemotherapy regimens. Median 6 (range 3–12) cycles were given with 6 off study with progression at 3–7 cycles. RECIST and CA125 responses are under review; in 11 pts with baseline CA125 of > 40 IU/mL, median increase was 31% by cycle 2; later falling to -57%. AEs did not exceed grade 3; hand-foot syndrome led to PLD dose reduction in 8 pts (33%); asymptomatic decreases in left ventricular ejection fraction (LVEF) >10% in 3 pts were noted, with treatment discontinuation in 1. The mean (±SEM) secondary PK parameter estimates for Cmax, AUC, and elimination half life were 4.5 ± 0.5 ug/mL, 651.7 ± 61 ug/mL x h, and 93.3 ± 19.7 h, respectively. Conclusions: Cycles 1 and 2 PLD PK do not differ. PLD + B is tolerable with PLD dose modifications. Declines in LVEF in 1 institution have uncertain causality. Midway into the trial, safety and time on study encourage completion for study primary endpoint. [Table: see text]

Phase III trial of non-pegylated liposomal doxorubicin (M) in combination with trastuzumab (T) and paclitaxel (P) in HER2+ metastatic breast cancer (MBC).

2013 ◽  
Vol 31 (15_suppl) ◽  
pp. 517-517 ◽  
Author(s):  
Lorena De La Pena ◽  
Javier Cortes ◽  
Alexey Manikhas ◽  
Laslo Roman ◽  
Vladimir Semiglazov ◽  
...  
Keyword(s):  
Nyha Class ◽  
Metastatic Breast ◽  
Pegylated Liposomal Doxorubicin ◽  
Progression Free Survival ◽  
Left Ventricular ◽  
Phase Iii ◽  
Left Ventricular Ejection ◽  
Class Iii ◽  
Ventricular Ejection Fraction ◽  
Phase Iii Trial

517 Background: M in combination with T has shown promising activity and cardiac safety in MBC patients (pts). We conducted a randomized Phase III trial of first-line M plus T and P (MTP) versus T plus P (TP) in HER2+ MBC pts. Methods: Pts with HER2+ (by FISH) MBC ≥ 18 years and ECOG 0-1, who had received no prior chemotherapy for metastatic disease, were eligible. Left ventricular ejection fraction should be within normal institutional limits. Prior (neo-) adjuvant anthracyclines, T or P were permitted, if completed >1 year before the start of the study. Pts received M 50 mg/m2 q3w for 6 cycles, T 4 mg/kg loading dose followed by 2 mg/kg qw, and P 80 mg/m2qw, or T+P at the same doses until progression or toxicity. Primary outcome was progression-free survival (PFS). Enrollment of 332 pts would provide 80% power with a 5% significance to detect an improvement in PFS with MTP, assuming a median PFS of 8 months in TP and a hazard ratio (HR) of 0.70. Results: 363 pts enrolled (MTP 181, TP 183), 360 received treatment. The two groups were well balanced for demographics, pretreatment characteristics and extent of disease. One third of the pts had prior exposure to anthracyclines, but almost none to trastuzumab (1% and 2% in MTP and TP arms, respectively). Six cycles of M could be given to 72% of the pts. With a median follow-up of 31 months, median PFS was 16.1 and 14.5 months with MTP and TP, respectively (HR 0.84, P=0.174). In pts with ER and PR-negative tumors, PFS was 20.7 and 14.0 months, respectively (HR, 0.68; 95% CI 0.47–0.99). Median overall survival (OS) was 33.6 and 28.9 months, respectively (HR, 0.79, P=0.083). In ER and PR-negative tumors, OS was 38.2 and 27.9 months, respectively (HR, 0.63; 95% CI 0.42–0.93). The incidence of NYHA Class III/IV congestive heart failure was 3% with MTP and there were 2 cardiac deaths with TP. The frequency of adverse events was higher with MTP, especially myelosuppression, stomatitis and gastrointestinal intolerance. Conclusions: The trial failed to demonstrate a significant clinical improvement with the addition of M to TP. The clinical benefit observed in an exploratory analysis in the ER and PR-negative population deserves consideration for further clinical trials. Clinical trial information: NCT00294996.

Phase I trial of pegylated liposomal doxorubicin and lapatinib in the treatment of metastatic breast cancer (MBC): Final results.

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. 610-610
Author(s):  
Mary E. Cianfrocca ◽  
Virginia G. Kaklamani ◽  
Steven T. Rosen ◽  
Jamie H. Von Roenn ◽  
Alfred Rademaker ◽  
...  
Keyword(s):  
Phase I ◽  
Liposomal Doxorubicin ◽  
Cardiac Toxicity ◽  
Metastatic Breast ◽  
Pegylated Liposomal Doxorubicin ◽  
Left Ventricular ◽  
Primary Objective ◽  
Left Ventricular Ejection ◽  
Ventricular Ejection Fraction ◽  
Grade 3

610 Background: Liposomal formulations including pegylated liposomal doxorubicin (PLD) were developed to improve the therapeutic index of anthracyclines (A). Lapatinib (L) is a selective, highly competitive inhibitor of ErbB1 and ErbB2 tyrosine kinases. Conventional doxorubicin plus trastuzumab was effective but with unacceptable cardiac toxicity. PLD plus L may be effective with less cardiac risk. Methods: This is a phase I, dose-escalation trial of PLD 20, 30, 45 and 60 mg/m2 IV every 4 weeks (maximum of 8 doses) and L, 1500 mg po daily until progression in patients (pts) with MBC. ErbB2 positivity was not required. Prior chemotherapy, endocrine therapy and trastuzumab were allowed. A subsequent amendment allowed prior L. Prior A use was limited to 240 mg/m2 of doxorubicin or 600 mg/m2 of epirubicin. Concomitant CYP3A4 inducers/ inhibitors were not allowed. A left ventricular ejection fraction (LVEF) of > 50% was required. The primary objective was to evaluate the safety (particularly cardiac), tolerability and feasibility of PLD and L. Results: 23 pts (PLD: 20 mg/m2 - 4 pts; 30 mg/m2 - 3 pts; 45 mg/m2 – 13 pts; 60 mg/m2- 3 pts) have been treated; total of 73 treatment cycles. Dose-limiting toxicity (DLT) was not reached. One pt had an LVEF drop to < 50% after 4 cycles accompanied by a pericardial effusion due to progressive disease. Treatment-related grade III/IV adverse events included: 4 pts with hand-foot-syndrome (HFS), 2 pts each with leukopenia, infection, and skin changes, 1 pt each with pain, fatigue, diarrhea, mucositis, hypoalbuminemia, anemia, cough, pleural effusion, and edema. Grade 3 HFS occurred in 2 of 3 pts in the 60 mg/m2 cohort. Response data in 21 evaluable pts: 4 PR, 5 SD, and 12 PD. Preliminary pharmacokinetic (PK) analyses (7 pts) indicate L has no effect on PLD (45 mg/m2) concentrations, but L concentrations were approximately 2-fold higher the day of PLD dosing. Conclusions: In 23 pts treated, PLD plus L was well tolerated with manageable toxicities and no treatment-related cardiac toxicity. DLT was not reached however grade 3 HFS occurred in 2 of 3 pts in the 60 mg/m2 cohort. Preliminary PK analyses demonstrate no effect of L on PLD, but an effect of PLD on L the day of PLD dosing.

Paclitaxel (P), pegylated liposomal doxorubicin (PLD) and trastuzumab as 1st-line chemotherapy (chemo) in HER2/neu-positive (+) metastatic breast cancer (MBC)

2006 ◽  
Vol 24 (18_suppl) ◽  
pp. 10663-10663 ◽  
Author(s):  
A. Karabelis ◽  
C. Kosmas ◽  
N. Mylonakis ◽  
G. Tsakonas ◽  
K. Evgenidi ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Metastatic Breast ◽  
Pegylated Liposomal Doxorubicin ◽  
Parent Drug ◽  
Response Duration ◽  
Left Ventricular ◽  
Left Ventricular Ejection ◽  
Ventricular Ejection Fraction ◽  
Her 2 ◽  
Grade 3

10663 Background: Addition of trastuzumab (Herceptin, H) to successive neoadjuvant taxane+anthracycline-based chemo in patients (pts) with HER-2 (+) breast cancer significantly increases the pathological complete response (CR) rates. PLD has considerably less cardiotoxicity compared to parent drug. The aim of the study was to evaluate the activity and safety of combining H with PLD and P as 1st-line chemo in HER-2 (+) MBC pts. Methods: Inclusion criteria were: histologically confirmed MBC or relapsed after adjuvant chemo, ≥1 measurable lesion, adequate organ function, ECOG-PS 0–1, left ventricular ejection fraction (LVEF) by MUGA ≥55% (reevaluated after cycles 3 and 6). HER-2 positivity was determined by IHC and confirmed with CISH. Chemo was administered as follows: H 6mg/kg (8mg/kg-1st cycle) infused over 90min, PLD 35mg/m2 over 1hr, and P 175mg/m2 over 3hrs on day 1, with prophylactic G-CSF, recycled every 3 weeks. In responders, H was administered as consolidation (6mg/kg/3wks) until disease progression. Results: From 10/2003–10/2005, 19 female HER-2 positive MBC pts were enrolled. Median age: 68 (range, 42–78). Metastatic sites were: lung 6, liver 1, bone 3, lymph nodes 11, soft tissue 5 [median: 2 (range, 1–4)]. Pts received a median of 6 (range, 1–8) for a total of 102 cycles. PLD was started at 35 mg/m2, but in pts with grade 3 hand-foot syndrome (HFS) dose was reduced by 25% (6 pts), or the drug was omitted for 1 cycle (1 pt). 17 pts completed 3–6 cycles and were evaluable for response, all treated patients were evaluable for toxicity. Response rates (RR) were 71%; CR 41%, PR 30%, SD 29%, with no PD. Two pts rendered operable had pCR. Toxicities were: HFS; grade 4: 1, grade 3: 6 (overall 37%), grade 3–4 neutropenia: 4, grade 3 anemia: 1, grade 3–4 mucositis: 2, and grade 2 alopecia: 19. Neither significant LVEF decline, nor symptomatic cardiac event was observed. It is too early to provide data on response duration, TTP, and OS, and these will be available at the meeting. Conclusions: H+P+PLD as 1st-line chemo in HER-2(+) MBC pts is a very active and well tolerated regimen with no significant morbidity/mortality. HFS was the most relevant toxicity. The study is ongoing. No significant financial relationships to disclose.

Carboplatin and Nonpegylated Liposomal Doxorubicin in Primary Advanced or Recurrent Endometrial Cancer: A Phase 2 Trial Conducted by AGO Austria

2015 ◽  
Vol 25 (2) ◽  
pp. 257-262 ◽  
Author(s):  
Birgit Volgger ◽  
Alain G. Zeimet ◽  
Alexander Reinthaller ◽  
Edgar Petru ◽  
Christian Schauer ◽  
...  
Keyword(s):  
Endometrial Cancer ◽  
Area Under The Curve ◽  
Progression Free Survival ◽  
Left Ventricular ◽  
Left Ventricular Ejection ◽  
Phase 2 ◽  
Ventricular Ejection Fraction ◽  
Free Survival ◽  
End Point ◽  
Grade 3

ObjectiveRecurrent/advanced endometrial carcinoma carries a poor prognosis. Chemotherapy usually consists of cisplatin/doxorubicin and paclitaxel or the doublet of carboplatin and paclitaxel.We report on final results of the Austrian phase 2 AGO trial of nonpegylated doxorubicin citrate and carboplatin in 39 patients with primary advanced or relapsed endometrial cancer. The main primary end point is response rate, and the main secondary end point is feasibility.MethodsThirty-nine patients received 60 mg/m2nonpegylated doxorubicin citrate and carboplatin (area under the curve, 5) every 3 weeks for 6 to 9 cycles or until progression. Best response during therapy, progression-free survival, and the toxicity profile were recorded.ResultsThirteen patients (33%) had primary advanced disease, and 26 patients (67%) had recurrent disease. Seventy-five percent of the tumors were adenocarcinomas, 15% were serous carcinomas, and 5% were clear cell and mixed müllerian carcinomas. We observed 1 complete response (3%) and 16 partial responses (41%) in the intention-to-treat population. The median progression-free survival was 7.2 months, and the median overall survival was 14.7 months. Overall, 177 cycles were administered; the mean number of cycles per patient was 4.5. Ten percent of patients received 9 cycles of chemotherapy, and 44% of patients received 6 cycles of chemotherapy. Grade 3/4 neutropenia occurred in 17%, grade 3/4 anemia in 5%, and grade 3/4 thrombopenia in 12% of the cycles. In 6% of the cycles, febrile neutropenia was noticed. Grade 3/4 nausea was seen in 5% of cycles. One patient (3%) experienced cardiac toxicity and had a reduction in the left ventricular ejection fraction to below 50%.ConclusionsThe reported combination demonstrates considerable activity and should be evaluated further.

Risk stratification in hf with mid-range LVEF: the role of cardiopulmonary exercise testing

2020 ◽  
Vol 41 (Supplement_2) ◽  
Author(s):  
B.M.L Rocha ◽  
G.J Lopes Da Cunha ◽  
P.M.D Lopes ◽  
P.N Freitas ◽  
F Gama ◽  
...  
Keyword(s):  
Risk Stratification ◽  
Exercise Testing ◽  
Primary Endpoint ◽  
Prognostic Significance ◽  
Cardiopulmonary Exercise Testing ◽  
Left Ventricular ◽  
Left Ventricular Ejection ◽  
Ventricular Ejection Fraction ◽  
Cardiopulmonary Exercise

Abstract Background Cardiopulmonary exercise testing (CPET) is recommended in the evaluation of selected patients with Heart Failure (HF). Notwithstanding, its prognostic significance has mainly been ascertained in those with left ventricular ejection fraction (LVEF) &lt;40% (i.e., HFrEF). The main goal of our study was to assess the role of CPET in risk stratification of HF with mid-range (40–49%) LVEF (i.e., HFmrEF) compared to HFrEF. Methods We conducted a single-center retrospective study of consecutive patients with HF and LVEF &lt;50% who underwent CPET from 2003–2018. The primary composite endpoint of death, heart transplant or HF hospitalization was assessed. Results Overall, 404 HF patients (mean age 57±11 years, 78.2% male, 55.4% ischemic HF) were included, of whom 321 (79.5%) had HFrEF and 83 (20.5%) HFmrEF. Compared to the former, those with HFmrEF had a significantly higher mean peak oxygen uptake (pVO2) (20.2±6.1 vs 16.1±5.0 mL/kg/min; p&lt;0.001), lower median minute ventilation/carbon dioxide production (VE/VCO2) [35.0 (IQR: 29.1–41.2) vs 39.0 (IQR: 32.0–47.0); p=0.002) and fewer patients with exercise oscillatory ventilation (EOV) (22.0 vs 46.3%; p&lt;0.001). Over a median follow-up of 28.7 (IQR: 13.0–92.3) months, 117 (28.9%) patients died, 53 (13.1%) underwent heart transplantation, and 134 (33.2%) had at least one HF hospitalization. In both HFmrEF and HFrEF, pVO2 &lt;12 mL/kg/min, VE/VCO2 &gt;35 and EOV identified patients at higher risk for events (all p&lt;0.05). In Cox regression multivariate analysis, pVO2 was predictive of the primary endpoint in both HFmrEF and HFrEF (HR per +1 mL/kg/min: 0.81; CI: 0.72–0.92; p=0.001; and HR per +1 mL/kg/min: 0.92; CI: 0.87–0.97; p=0.004), as was EOV (HR: 4.79; CI: 1.41–16.39; p=0.012; and HR: 2.15; CI: 1.51–3.07; p&lt;0.001). VE/VCO2, on the other hand, was predictive of events in HFrEF but not in HFmrEF (HR per unit: 1.03; CI: 1.02–1.05; p&lt;0.001; and HR per unit: 0.99; CI: 0.95–1.03; p=0.512, respectively). ROC curve analysis demonstrated that a pVO2 &gt;16.7 and &gt;15.8 mL/kg/min more accurately identified patients at lower risk for the primary endpoint (NPV: 91.2 and 60.5% for HFmrEF and HFrEF, respectively; both p&lt;0.001). Conclusions CPET is a useful tool in HFmrEF. Both pVO2 and EOV independently predicted the primary endpoint in HFmrEF and HFrEF, contrasting with VE/VCO2, which remained predictive only in latter group. Our findings strengthen the prognostic role of CPET in HF with either reduced or mid-range LVEF. Funding Acknowledgement Type of funding source: None

P962Follow-up of protected high-risk percutaneous coronary intervention with microaxial Impella pump. Results from the retrospective German Impella Registry

2019 ◽  
Vol 40 (Supplement_1) ◽  
Author(s):  
S Baumann ◽  
N Werner ◽  
F Al-Rashid ◽  
A Schaefer ◽  
T Bauer ◽  
...  
Keyword(s):  
Percutaneous Coronary Intervention ◽  
High Risk ◽  
Primary Endpoint ◽  
Coronary Intervention ◽  
Left Ventricular ◽  
Ventricular Assist Devices ◽  
Left Ventricular Ejection ◽  
Ventricular Ejection Fraction ◽  
Percutaneous Coronary

Abstract Background Percutaneous coronary intervention (PCI) presents a relevant alternative to coronary bypass surgery for the treatment of patients with complex coronary artery disease and high perioperative risk. By temporary implantation of a percutaneous ventricular assist devices (pVAD) interventionalists attempt to anticipate the hemodynamic risk of those high-risk patients in a so-called protected PCI. The Impella® system presents the currently most common device for protected PCI and could show hemodynamic stability in earlier trials. Methods This study is a retrospective, observational multi-center registry of ten hospitals in Germany. We included patients undergoing protected high-risk PCI with Impella® support. The primary endpoint was defined as major adverse cardiac events (MACE) during a 180-day follow-up and consisted of all-cause mortality, myocardial infarction (MI) and stroke. Results Six of the participating hospitals performed a follow-up. In total, 157 patients (80.3% male; mean age 71.8±10.8 years) were included in the present study. Prior to PCI, median left ventricular ejection fraction was 39.0% (25.0%-50.0%) and median SYNTAX-Score I was 33.0 (24.0–40.5). The 180-day follow-up was available for 149 patients (94.9%). Eight patients (5.1%) were lost to follow-up. During the follow-up period, 34 patients (22.8%) suffered from a MACE. A total of 27 patients (18.1%) died. Nine patients (6.0%) sustained a MI, while 4 patients (2.7%) had a stroke. Kaplan-Meier curves for primary endpoint Conclusions Patients undergoing protected high-risk PCI with Impella® support show a good 180-day clinical outcome regarding rates of MACE and mortality. However, a head-to-head comparison of Impella supported patients to protected PCI with other pVADs is pending. Acknowledgement/Funding S.B., N.W., F.A.-R., J.-M.S., A.S., R.S., I.A. receive consulting fees/honoraria from Abiomed (Danvers, MA, USA).

The combination of the HER2 antibody trastuzumab, the EGFR tyrosine kinase inhibitor gefitinib, and docetaxel as first-line therapy in patients with HER2 overexpressing stage IV breast carcinoma

2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 1057-1057
Author(s):  
G. Somlo ◽  
M. Koczywas ◽  
T. Luu ◽  
M. McNamara ◽  
V. Bedell ◽  
...  
Keyword(s):  
Performance Status ◽  
Stage Iv ◽  
Left Ventricular ◽  
Left Ventricular Ejection ◽  
Time To Progression ◽  
Ecog Performance Status ◽  
Ventricular Ejection Fraction ◽  
Grade 3 ◽  
Topo Ii ◽  
To Receive

1057 Background: Interference with both HER2 and epidermal growth factor (EGFR) dependent pathways may improve therapeutic efficacy of docetaxel (doc) in pts with HER2 overexpressing (+) BC. Methods: Patients (pts) without prior chemotherapy (Rx) exposure for stage IV HER-2 + BC were enrolled. Prior hormonal or adjuvant Rx inclusive of taxane or trastuzumab (tras) were allowed. A left ventricular ejection fraction of > 45% and ECOG performance status of ≥ 2 were required. Pts were to receive doc 75 m2, tras every 3 weeks, and gefitinib (gef) 250 mg daily. BC samples from 12 pts were analyzed by FISH for HER2 and EGFR amplification (amp), and topoisomerase II (topo II) amp or loss. IHC was to be performed to examine p-Src, p-STAT3, Ki67 and survivin expression. Results: The median age was 49 (range, 34–67) and ECOG performance status 0.5 (0–1). The first 9 patients received gef 250 mg daily; 2 pts received dox 75 mg/m2 and developed grade 3 febrile neutropenia (neu), hence, additional pts received doc at 60 mg/m2: 3 more episodes of grade 3 neu were seen. Gef was held due to grade 3 dermatitis (2 pts) and diarrhea (2 pts). Pts received a median of 6 cycles (3–10). Gef schedule then was changed, and was prescribed on days 2–14, only. Three of the next 9 pts experienced grades 3 or 4 neu, and we observed 3 cases of grade 3 gastrointestinal toxicities; pts were able to receive 11 + (range; 5–25+) cycles on this schedule (p<0.04). There were 4 complete (CR)and 6 partial R (23 % CR, 59 % overall R), and 3 pts had stable disease (SD; all R and SD confirmed); 3 pts progressed at 4, 4, and 5 mos, 1 pt was inevaluable. The median time to progression is 12 + mos. Samples from 3 pts revealed topo II amplification and one pt sample showed loss of one topo II allele; none were amplified for EGFR. Outcome will be correlated with IHC defined signal trasduction status and proliferation rates. Conclusions: The combination of doc, tras, and short course of gef is feasible, with encouraging R and SD rates and time to progression. Further exploration of simultaneous blockage of multiple signal transduction pathways is indicated in combination with chemoRx. Supported by NCI CA33572 and by a grant from AstraZeneca. No significant financial relationships to disclose.

MC044h, a phase II trial of sorafenib in patients (pts) with metastatic neuroendocrine tumors (NET): A Phase II Consortium (P2C) study

2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 4504-4504 ◽  
Author(s):  
T. J. Hobday ◽  
J. Rubin ◽  
K. Holen ◽  
J. Picus ◽  
R. Donehower ◽  
...  
Keyword(s):  
Growth Factor ◽  
Neuroendocrine Tumors ◽  
Phase Ii ◽  
Primary Endpoint ◽  
Treatment Options ◽  
Growth Factor Receptor ◽  
Progression Free Survival ◽  
Uncontrolled Hypertension ◽  
Eligibility Criteria ◽  
Grade 3

4504 Background: Treatment options for metastatic NET, including islet cell carcinoma (ICC) and carcinoid tumor (CT), are limited. These tumors frequently express vascular endothelial growth factor receptor-2 (VEGFR-2) and platelet derived growth factor receptor receptor-β (PDGFR-β). Sorafenib, a small-molecule inhibitor of the VEGFR-2 and PDGFR-β tyrosine kinase domains, is a rational targeted therapy to evaluate in NET. Methods: Eligibility criteria included: ECOG PS = 2, = 1 prior chemotherapy, good organ function and signed informed consent. Prior interferon and prior or concurrent octreotide at a stable dose were allowed. Pts unable to take oral medications, with uncontrolled hypertension or with symptomatic coronary artery disease were excluded. Pts received sorafenib 400 mg po BID. Primary endpoint was response by RECIST in two cohorts (ie, CT and ICC) using separate 2-stage phase II designs. Results: 93 pts were enrolled: (50 CT, 43 ICC). For pts evaluable for the primary endpoint, 4 of 41 (10%) CT pts and 4 of 41 (10%) ICC pts had a PR. There were 3 minor responses (MR = 20–29% decrease in sum of target lesion diameters) in CT pts and 9 MRs in ICC pts for PR+MR rate of 17% for CT pts and 32% for ICC pts. For pts evaluable, 6-month progression-free survival was observed in 8/20 CT and 14/23 ICC pts. Grade 3–4 toxicity occurred in 43% of pts, with skin (20%), GI (7%) and fatigue (9%) most common. Translational studies from tumor tissue will be presented. Conclusions: Sorafenib at 400 mg po BID has modest activity in metastatic neuroendocrine tumors, with frequent grade = 3 toxicity. Supported by NOI CM6225. No significant financial relationships to disclose.

Pegylated liposomal doxorubicin in combination with gemcitabine in elderly women with locally advanced or metastatic breast cancer: Safety and activity results of our clinical experience

2009 ◽  
Vol 27 (15_suppl) ◽  
pp. e12005-e12005
Author(s):  
B. Adamo ◽  
T. Franchina ◽  
N. Denaro ◽  
C. Garipoli ◽  
G. Ferraro ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Advanced Breast Cancer ◽  
Clinical Benefit ◽  
Liposomal Doxorubicin ◽  
Elderly Women ◽  
Pegylated Liposomal Doxorubicin ◽  
Left Ventricular ◽  
Advanced Breast ◽  
Left Ventricular Ejection ◽  
Grade 3

e12005 Background: Elderly breast cancer patients have an increased risk of toxicity from chemotherapy, especially from anthracycline-based regimens. Pegylated liposomal doxorubicin (PLD) has shown a better tolerability profile also in combination with gemcitabine (GEM), as evidenced in several phase II trials. The aim of this study is to retrospectively evaluate the safety and activity of this combination in chemo-naïve or pre-treated elderly patients with advanced breast cancer. Methods: From January 2006 to March 2008, 39 patients (pts) with age ≥ 65 received, at our institution, PLD 25 mg/m2 (day 1, q21) and GEM 800 mg/m2 (days 1 and 8, q21). Median age was 72 (range, 65–79). ECOG PS was 0/1/2 in 14/23/2 pts, respectively. 12 pts (31%) were chemo-naïve, 20 (51%) received prior adjuvant anthracycline-based regimens, and 7 (18%) received other chemotherapies. PLD-GEM combination was administered as first line in 35 pts (90%). Median left ventricular ejection fraction (LVEF) at baseline was 61% (range, 50%-75%). 28 patients (72%) had metastatic disease: 10 in liver, 6 in lung, 2 in skin, and 10 in multiple sites. Estrogen receptor was positive in 32 pts (82%); HER-2+ in 5 pts; 7 pts were triple negative. Results: A total of 206 cycles were administered with a mean number of cycles per patient of 5.2 (range, 3–12). Grade 3–4 neutropenia occurred in 4 (10%) and 3 patients (8%), respectively; grade 3 anemia in two pts (5%). Non-hematological toxicity was mild, with 5 cases (13%) of grade 3 mucositis, and 2 cases (5%) of grade 2 palmar-plantar erythrodysesthesia syndrome. No modifications in LVEF or toxic deaths were documented. We observed 1 CR (2.5%) and 11 PR (28.2%). Eighteen (44%) patients experienced SD for 16 weeks and an overall clinical benefit of 76.8%. Conclusions: The combination of PLD and GEM has a favorable tolerability and a safety profile with an evident clinical benefit and should represent an interesting treatment option in elderly women with advanced breast cancer. No significant financial relationships to disclose.

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