Effect of lenalidomide (LEN) on biochemical responses and clinical benefit (CB) as a single agent in chemotherapy-naive castration-resistant prostate cancer (CRPC).

2012 ◽  
Vol 30 (5_suppl) ◽  
pp. 128-128 ◽  
Author(s):  
Chadi Nabhan ◽  
Anand Patel ◽  
Dana Villines ◽  
Kathy Tolzien ◽  
Susan K. Kelby ◽  
...  
Keyword(s):  
Adverse Events ◽  
Clinical Benefit ◽  
Single Agent ◽  
Complete Response ◽  
Median Number ◽  
Castration Resistant Prostate Cancer ◽  
Serious Adverse Events ◽  
Biochemical Responses ◽  
Grade 3 ◽  
Dose Reductions

128 Background: LEN has anti-angiogenesis and immunomodulatory properties making it ideal to investigate in CRPC. We report on a phase II study investigating LEN in chemotherapy-naïve CRPC patients (pts) Methods: Eligible pts received LEN at 25 mg daily on days 1 – 21 every 28-days until progression. Daily aspirin or coumadin were required. Responses were assessed every 2 cycles. Toxicity was assessed every cycle. Primary end point: The CB of LEN [Sum of complete response (CR), partial response (PR) and stable disease (SD)]. Secondary end points: Toxicity, time to radiographic and PSA progression (TTP and TTP-PSA), time to next treatment (TTNT), overall survival (OS), and LEN’s impact on quality of life (QOL). Results: 31 pts were enrolled; 27 response-evaluable (1 withdrew consent, 3 off per choice after adverse events). Median age is 74 (range 58-89) with 24 (77%) having Gleason ≥ 7 disease. Median PSA is 66 (2.1-918.6). Six pts (19%) had liver/lung involvement. Fourteen pts (51%) showed biochemical response with 4 (15%) having >50% PSA drop. TTP-PSA is 4 months (2-11). No radiographic responses seen but 17 pts had SD for a median of 4 months (2-16) (CB=55%). Median number of LEN cycles was 3 (2-15). With a median follow-up of 18 months (5-38), 17 patients (55%) remain alive; median OS of 18 months. Grade 3/4 hematologic toxicities were most common (neutropenia 41%, leukopenia 12%, anemia 9%, thrombocytopenia 9%). Other grade 3/4 toxicities: venothromboembolism, atrial fibrillation, and dehydration (6% each). Serious adverse events (SAEs) were witnessed in 10 pts (32%) with only 1 (3%, rash) definitely related to LEN. Others were not related or possibly related. Of 27 pts, 7 (26%) had a dose reduction and 2 (7%) required two dose reductions. Dose reductions occurred after cycle 3. QOL scales suggested no adverse impact. Median TTNT is 2 months (9 pts received chemotherapy, 10 pts went onto studies, 3 pts received hormonal therapies, 4 pts received radiation, 3 pts had no therapy yet, and 2 pts remain on LEN). Conclusions: LEN is active as monotherapy in CRPC. Biochemical responses are witnessed and clinical benefit is observed. Myelosuppression is the most common toxicity.

Effect of sorafenib on chemotherapy resistance and refractoriness in castration-resistant prostate cancer (CRPC)

2009 ◽  
Vol 27 (15_suppl) ◽  
pp. e16105-e16105
Author(s):  
C. Nabhan ◽  
K. Tolzien ◽  
T. M. Lestingi ◽  
A. Galvez ◽  
J. D. Bitran
Keyword(s):  
Clinical Benefit ◽  
Kinase Inhibitor ◽  
Chemotherapy Resistance ◽  
Complete Response ◽  
Median Number ◽  
Castration Resistant Prostate Cancer ◽  
Chemotherapy Agent ◽  
Hand Foot Syndrome ◽  
Psa Response ◽  
Grade 3

e16105 Background: There is no standard for CRPC once chemotherapy fails. In studies employing docetaxel (D), 35–39% of pts did not complete therapy due to progression and only 45–50% had a PSA response. This implies that many pts develop resistance to D. Sorafenib is a multi kinase inhibitor with antiangiogenesis properties. We hypothesized that sorafenib could overcome chemotherapy resistance in these pts. Methods: Eligible pts must have progressed while on either D or mitoxantrone (M). They received sorafenib at 400 mg orally twice/daily in addition to the chemotherapy agent they were on. Sorefinib/chemotherapy combination was given for a maximum of 6 cycles followed by sorafenib monotherapy until progression. Primary end point was safety of the sorafenib/chemotherapy combination. Secondary end points included the overall clinical benefit calculated as the sum of complete response (CR), partial response (PR), and stable disease (SD), toxicity, and time to disease progression (TTP). Results: To date, 15 pts have been enrolled; 14 are evaluable. Eleven pts were on D and 4 on M. Median age was 68 (range 61–83), median PSA was 111.2 ng/ml (13.6–1703.9). Nine pts (60%) had visceral and bone disease. Median PSA-DT pre-study was 2 months (0.5–6) and median time from last chemotherapy to starting study was 4 weeks. Median number of given cycles was 6.5 (2–12). Six pts did not require dose reduction, 2 others were re-escalated to the full dose. Sorafenib was safely combined with chemotherapy with 6 pts experiencing grade 3 fatigue, 3 developing grade 3 hand/foot syndrome, and 1 experiening grade 3 diarrhea. Eleven pts (73%) had SD radiographically that lasted a median of 6.7 months. In all, 6 out of 14 pts (42%) had a PSA decline after adding sorafenib and 3 (21%) had stable PSA. Of these 9 pts (PR+SD), 2 never doubled their PSA. Two pts had PSA decline after withdrawing sorafenib. Median TTP for PSA was 3.75 months. PSA responses did not correlate with radiographic changes or clinical benefit. With a median follow-up of 8 months, 5 pts (33%) remain alive with 1 continuing on therapy without progression. Conclusions: Sorafenib overcomes chemotherapy-refractoriness and failures in CRPC. [Table: see text]

Maintenance GM-CSF in patients with castration-resistant prostate cancer (CRPC) who maximized their response to chemotherapy

2009 ◽  
Vol 27 (15_suppl) ◽  
pp. e16155-e16155
Author(s):  
J. D. Bitran ◽  
K. Tolzien ◽  
T. M. Lestingi ◽  
C. Nabhan
Keyword(s):  
Clinical Benefit ◽  
Response Duration ◽  
Complete Response ◽  
Median Number ◽  
Castration Resistant Prostate Cancer ◽  
Median Response ◽  
Gm Csf ◽  
Castration Resistant ◽  
Response To Chemotherapy ◽  
Grade 3

e16155 Background: There is no standard treatment for CRPC patients (pts) who completed chemotherapy. Time to progression (TTP) ranges from 3–6 months after stopping chemotherapy. GM-CSF (GM) is an immune-based growth factor with reported activity in CRPC. We hypothesized that GM maintenance in pts who have maximized their response to chemotherapy could delay TTP or time to next treatment (TNT). Methods: Eligible pts were those with CRPC who completed 10–12 cycles of docetaxel (D) or mitoxantrone (M) chemotherapy without progression; or those who maximized their response to chemotherapy before completing 10–12 cycles. Maximum response was defined as a <10% change in PSA repeated on two occasions with stable disease (SD) radiographically. Enrolled pts received GM at 250 ug/m2 subcutaneously for 14 days followed by 14-days of rest. GM was continued until disease progression. Primary end point was the clinical benefit defined as the sum of partial response (PR), complete response (CR) and SD. Secondary end points included toxicity, TTP, and TNT. Results: To date, 12 pts out of planned 20 have been enrolled (9 were on D and 3 on M). Median age was 78 (66–96). Median PSA at enrollment was 56.5 (0.1–566). Only 1 pt had a Gleason score < 7. Median time from initial diagnosis to GM was 70 months. Median number of chemotherapy cycles prior to GM was 9 (6–12). Eight pts (66%) had visceral and bone disease. GM was well-tolerated with no drug-related grade 3 and/or 4 toxicities. Ten pts are evaluable (1 pt withdrew consent and another did not comply). Median GM cycles received so far was 3 (2–11). With a median follow up of 11 months (2–17), 3 pts demonstrated SD and 2 had PR for an overall clinical benefit of 50%. One pt remains on study at 7 months while the median response duration for the other 4 responding pts was 7 months. Four pts never received another treatment but the median TNT in other evaluable pts was 3 months. Conclusions: GM is safe, well tolerated, and has activity in CRPC after stopping chemotherapy. Combining chemotherapy with GM should be investigated in future studies. [Table: see text]

scholarly journals Efficacy of Ruxolitinib in Patients With Chronic Neutrophilic Leukemia and Atypical Chronic Myeloid Leukemia

2020 ◽  
Vol 38 (10) ◽  
pp. 1006-1018 ◽  
Author(s):  
Kim-Hien T. Dao ◽  
Jason Gotlib ◽  
Michael M.N. Deininger ◽  
Stephen T. Oh ◽  
Jorge E. Cortes ◽  
...  
Keyword(s):  
Chronic Myeloid Leukemia ◽  
Adverse Events ◽  
Myeloid Leukemia ◽  
Response Rate ◽  
Symptom Assessment ◽  
Complete Response ◽  
Serious Adverse Events ◽  
Chronic Neutrophilic Leukemia ◽  
Atypical Chronic Myeloid Leukemia ◽  
Grade 3

PURPOSE Colony-stimulating factor-3 receptor ( CSF3R)-T618I is a recurrent activating mutation in chronic neutrophilic leukemia (CNL) and to a lesser extent in atypical chronic myeloid leukemia (aCML) resulting in constitutive JAK-STAT signaling. We sought to evaluate safety and efficacy of the JAK1/2 inhibitor ruxolitinib in patients with CNL and aCML, irrespective of CSF3R mutation status. METHODS We conducted a phase II study of ruxolitinib in 44 patients (21 CNL and 23 aCML). The primary end point was overall hematologic response rate (ORR) by the end of 6 continuous 28-day cycles for the first 25 patients enrolled. We considered a response as either partial (PR) or complete response (CR). We expanded accrual to 44 patients to increase our ability to evaluate secondary end points, including grade ≥ 3 adverse events, spleen volume, symptom assessment, genetic correlates of response, and 2-year survival. RESULTS ORR was 32% for the first 25 enrolled patients (8 PR [7 CNL and 1 aCML]). In the larger cohort of 44 patients, 35% had a response (11 PR [9 CNL and 2 aCML] and 4 CR [CNL]), and 50% had oncogenic CSF3R mutations. The mean absolute allele burden reduction of CSF3R-T618I after 6 cycles was greatest in the CR group, compared with the PR and no response groups. The most common cause of death is due to disease progression. Grade ≥ 3 anemia and thrombocytopenia were observed in 34% and 14% of patients, respectively. No serious adverse events attributed to ruxolitinib were observed. CONCLUSION Ruxolitinib was well tolerated and demonstrated an estimated response rate of 32%. Patients with a diagnosis of CNL and/or harboring CSF3R-T618I were most likely to respond.

A Pilot Study of Genasense® (Oblimersen Sodium, Bcl-2 Antisense Oligonucleotide), Fludarabine and Rituximab in Previously Treated and Untreated Subjects with Chronic Lymphocytic Leukemia.

Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 4827-4827 ◽  
Author(s):  
Asher Alban Chanan-Khan ◽  
Blanche Mavromatis ◽  
Kanti R. Rai ◽  
Philomena Casey ◽  
Steven Novick ◽  
...  
Keyword(s):  
Adverse Events ◽  
Lymphocyte Count ◽  
Alkylating Agents ◽  
Single Agent ◽  
Tumor Lysis Syndrome ◽  
Lymphocytic Leukemia ◽  
Serious Adverse Events ◽  
Reduced Dose ◽  
Previously Treated ◽  
Grade 3

Abstract Bcl-2 is an anti-apoptotic protein closely linked to chemotherapy resistance and inferior survival in patients (pts) with CLL. Genasense(GNS) enhances apoptosis induced by fludarabine (F), dexamethasone, and rituximab (R) in vitro, and has limited single-agent activity in heavily pre-treated CLL pts. Down-regulation of Bcl-2 may further sensitize CLL cells to apoptosis induced by F and R without exposing subjects to the toxicity of alkylating agents. CLL and NHL pts occasionally exhibit a “cytokine release syndrome” (spiking fever, back pain, and occasional hypotension) with GNS treatment. We hypothesized that a “step dosing” approach with GNS, similar to that sometimes used for R, could ameliorate these effects and allow safe and effective combination of this agent with F and R. We are currently evaluating this combination in pts with either previously untreated (UT) or relapsed, previously treated (PT) CLL who require systemic treatment. Eligibility includes: plts ≥ 50,000/mm3; serum Cr ≤ 1.5 mg/dL; adequate organ function; negative Coombs; no history of autoimmune hemolytic anemia. In cycle 1, GNS is given by continuous intravenous infusion at 1.5 mg/kg/d days 1 to 7. R is given on a dose-escalating schema (day 4, 125 mg/m2; day 6, 250 mg/m2). F (25 mg/m2/d) is given on days 6 to 8. In subsequent 28-day cycles (up to 6), the dose of GNS is escalated to 3 mg/kg/d days 1 to7 days, with R 375 mg/m2 on day 5 and F days 5 to7. To date, 20 pts have been enrolled (17 PT and 3 UT). Characteristics included: median age, 62 yrs (range 39 to 82 yrs); Rai stage III (2 pts) and IV (6 pts). Prior to administration of either F or R, single-agent GNS treatment at the initial reduced dose in Cycle 1 resulted in a median decrease in lymphocytes of 15% (among all patients regardless of decline in lymphocyte count) (Baseline: 48.3 cells x 103/ml; day 4: 40.1 cells x 103/ml). For the 13 pts who experienced a decline in lymphocyte count in cycle 1 prior to F and R, the median percentage change was 17%, with 4 pts having a &gt; 25% decrease. Three PT pts discontinued from study treatment prior to completing 6 cycles, 2 due to disease progression, and 1 with Grade 3 thrombocytopenia that was unresolved after 4 weeks. Among the 20 pts treated to date (9 ongoing), the most common grade 3 or higher adverse events have been neutropenia, pyrexia and thrombocytopenia. Serious adverse events have been noted in only 6 of 20 pts (all PT pts) and have included 2 pts with fever (1 neutropenic), 2 R infusion reactions, 1 lymph node abscess and 1 tumor lysis syndrome (with sepsis). Conclusions: 20 pts have been treated with combination GNS, F and R. Single-agent activity with GNS has been observed at a reduced dose of 1.5 mg/kg/d in cycle 1. The “step dosing” approach appears to be a well-tolerated, alternative approach to the administration of GNS. Further details of safety and efficacy will be presented.

High-Dose Cyclophosphamide: An Effective Non-Transplant Salvage Option in Relapsed/Refractory Multiple Myeloma.

Blood ◽  
2009 ◽  
Vol 114 (22) ◽  
pp. 4947-4947
Author(s):  
Sikander Ailawadhi ◽  
Michael Keng ◽  
Eddie Thara ◽  
Andrew Hendifar ◽  
Tanya Price ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Adverse Events ◽  
Median Time ◽  
Clinical Benefit ◽  
Single Agent ◽  
Staging System ◽  
Median Number ◽  
High Dose ◽  
Advanced Stage ◽  
Stage Disease

Abstract Abstract 4947 Background Recent advances in the treatment of multiple myeloma (MM) have significantly improved overall survival. With MM patients living longer, there is a constant need to find better therapeutic options, especially when patients are refractory to conventional agents, and are not eligible for experimental therapeutics in clinical trials. We evaluated treatment with single-agent high-dose cyclophosphamide (HDCy) in a cohort of heavily pre-treated patients with relapsed/refractory MM. Methods All the patients were previously treated for active MM at the University of Southern California (USC), Los Angeles, CA. Cyclophosphamide was administered at 1.2 gm/m2 in D5W intravenous (IV) over 1 hour every 3 hours for a total of 4 doses. Mesna was given to prevent urinary adverse events from cyclophosphamide as 4 gm/m2 in 1000 ml D5W IV to run at 50 ml/hr for 20 hours, starting 15 minutes prior to the first dose of cyclophosphamide. Patients were given pre-medications with 5HT3 antagonists an steroids. Treatment was administered in the in-patient setting and patients were discharged after the last dose of cyclophosphamide. Treatment was repeated every 4 weeks, if well-tolerated and continued response. Growth factor support was provided to the patients, as needed. Response to treatment was assessed after each 4-week cycle according to the International Uniform Response Criteria for MM. Results Seven patients (4 females, 3 males) were treated on this regimen with a median age of 53 years (range 34-61 yrs). These patients included 3 Hispanics (43%), 2 Asians (29%), 1 Caucasian (14%) and 1 African-American (14%). MM subtype was IgG disease in 3, IgA in 2, and light-chain only in 2 patients. Advanced stage disease (>stage 1) at the time of diagnosis as per the Durie Salmon (DS) staging system was present in 71% of the patients, while 3 patients (43%) had advanced stage disease as per the International Staging System (ISS). Four patients (57%) had lytic bone disease at the time of diagnosis, while only 1 patient was a non-secretor. Five of these patients (71%) never received an autologous stem cell transplant (ASCT) as a part of their MM treatment. Median number of therapies in these patients was 5 (range 4-8), while median number of therapies prior to high-dose cyclophosphamide (HDCy) were 3 (range 2-7). Median number of cycles of HDCy administered to the patients was 2 (range 1-5). Overall Response Rate (ORR = CR+PR) was 29% (n=2) with 1 patient achieving CR and 1 patient achieving VGPR. Four patients (57%) had stable disease (SD) and 1 patient had progressive disease (PD). Thus, the overall clinical benefit (CR+PR+SD) was seen in 6 out of the 7 patients (86%). Median time to best response was 5 weeks (range 4-10 weeks). Median time to progression was 16 weeks (range 8-24 weeks). Most common adverse events were cytopenias and fatigue, but were easily manageable with supportive care on an out-patient basis. Conclusions Despite improvement in therapeutic regimens for MM, it remains an incurable disorder. There is a constant need to develop regimens for treatment of relapsed/refractory MM patients that are efficacious and well-tolerated. We report the use of single-agent HDCy in heavily pre-treated MM patients. Despite the small number of patients studied, we have noted meaningful clinical benefit with a manageable toxicity profile. This warrants further investigation into developing therapeutic regimens with high-dose cyclophosphamide. Disclosures No relevant conflicts of interest to declare.

Neoadjuvant weekly nab-paclitaxel (wA), carboplatin (Cb) plus bevacizumab (B) with or without dose-dense doxorubicin-cyclophosphamide (ddAC) plus B in ER+/HER2-negative (HR+) and triple-negative (TN) breast cancer (BrCa): A BrUOG study.

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. 1045-1045 ◽  
Author(s):  
Natalie Faye Sinclair ◽  
Maysa M. Abu-Khalaf ◽  
Tina Rizack ◽  
Kayla Rosati ◽  
Gina Chung ◽  
...  
Keyword(s):  
Clinical Stage ◽  
Pathologic Complete Response ◽  
Complete Response ◽  
Residual Cancer ◽  
Serious Adverse Events ◽  
Residual Cancer Burden ◽  
Grade 3 ◽  
Gi Bleed ◽  
Dose Dense ◽  
Dose Reductions

1045 Background: High risk BrCa patients (pts) often receive weekly paclitaxel (wP) as well as ddAC. Switching to wA(Abraxane) or adding B or Cb may enhance its efficacy, especially in TN pts. Methods: Pts with clinical stage IIA-IIIC BrCa received wA 100 mg/m2, Cb AUC 6 + B 15 mg/kg q3wks x 12 wks only (cohort 1/Yale) or followed by ddAC + B x 4 (cohort 2/Brown). Endpoints: pathologic complete response (pCR) - absence of invasive BrCa in breast + axillary nodes, residual cancer burden (RCB), clinical CR/partial response (cCR/cPR), and toxicity. Correlative studies are being performed on biopsies obtained at baseline and after run-in doses of wA or B only. Post-op pts resume B for 34 wks; other systemic therapy, including ddAC in cohort 1, is at MD discretion. Results: 55 of 60 pts (median age 47, range 25-68; 31 HR+/29 TN) are evaluable for response (see table below). Median # doses wA 11,Cb 4, ddAC 4. Dose reductions: wA 25% for neutropenia (ANC), Cb 15% for thrombocytopenia (tcp). B 7% held for hypertension. Grade 3-4 toxicities (>5%): ANC 85%, tcp 35%, anemia 25%. Serious adverse events during wA: 3 nausea/dehydration (N/D), 3 infection w/o neutropenic fever (FN), 2 GI bleed; during ddAC: 6 (21%) FN despite G-CSF, 3 N/D. Conclusions: The combination of wA, q3wk Cb + B was well tolerated, with cCR+cPR 84%. However, overall pCR was only 11% (27% in TN) after 12 wks of this regimen (cohort 1). Subsequent preop ddAC raised overall pCR to 54%, and 81% in TN, demonstrating that longer treatment duration or inclusion of anthracycline-based therapy improves responses. Results for cohort 2 compare favorably with those from I-SPY, GeparQuinto and NSABP B-40; the addition of Cb and/or B in TN is being evaluated in CALGB 40603. [Table: see text]

Association of immune-related adverse events (irAEs) with improved clinical outcome in sarcoma patients treated with immune checkpoint blockade (ICB).

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. 11510-11510 ◽  
Author(s):  
Evan Rosenbaum ◽  
Kenneth Seier ◽  
Ciara Marie Kelly ◽  
Hannah Kiesler ◽  
Moriah Martindale ◽  
...  
Keyword(s):  
Adverse Events ◽  
Clinical Benefit ◽  
Performance Status ◽  
Progression Free Survival ◽  
Complete Response ◽  
Immune Checkpoint Blockade ◽  
Improved Outcomes ◽  
Comparison Results ◽  
Category Comparison ◽  
Grade 3

11510 Background: IrAEs are associated with improved clinical outcomes after treatment with ICB in select epithelial malignancies. We hypothesized that sarcoma patients (pts) treated with ICB who developed an irAE would have improved outcomes compared to pts who had no irAE. Methods: Adverse events (AEs) from 3 sarcoma-specific ICB trials (nivolumab plus NKTR-214, pembrolizumab plus epacadostat, and pembrolizumab plus T-VEC) were reviewed. AEs probably or definitely related to ICB were classified as immune- or non-immune-related by the principal investigator. Endpoints of interest included best overall response (BOR) by RECIST 1.1 (complete response [CR]/partial response [PR]), durable clinical benefit (DCB; CR/PR/stable disease [SD] ≥ 16 weeks), and progression-free survival (PFS). Outcomes were stratified by the presence or absence of ≥ 1 irAE of any grade and by grade 1-2, grade 3-4, or no irAE (three-category comparison). Results: A total of 124 pts received ICB on these studies. Median pt age was 56 (range: 13-90); 53% were male; all but one pt had a performance status of ≤ 1. BOR was PR in 12 pts, SD in 41, and PD in 69. 2 pts were not evaluable. 40 pts (32%) had ≥ 1 irAE of any grade, 6 of whom had a grade 3-4 irAE. The most common irAEs (≥ 5% of pts) were rash (15%), arthralgia (11%), myalgia (9%), pruritis (8%), and hypothyroidism (6%). The proportion of pts with a CR/PR was higher in pts with than without an irAE (18% vs. 6%, respectively; P = 0.058). A significantly higher proportion of pts with an irAE had DCB compared to those without (53% and 29%, respectively; P = 0.017). The median PFS of pts with an irAE was 16.6 months compared to 10.6 in those without (P = 0.013). The proportion of pts with a grade 3-4 irAE and a CR/PR was highest (33%) compared to pts with grade 1-2 (15%) or no irAE (6%) (P = 0.048). More pts with grade 3-4 irAE achieved DCB (67%) than grade 1-2 (50%) or no irAE (29%) (P = 0.027). Median PFS was 22.6, 15, and 10.6 weeks in the grade 3-4, grade 1-2, and no irAE groups, respectively (P = 0.047). Conclusions: Approximately one-third of advanced sarcoma pts with ICB-based immunotherapy developed an irAE. As reported previously in select carcinomas, sarcoma pts with irAEs were more likely to have clinical benefit than those without irAEs. Further research is needed to understand the mechanism behind this association and to validate these findings prospectively.

scholarly journals Feasibility and Safety of 3-Weekly Carboplatin/Paclitaxel Regimen in Advanced Squamous cell Carcinoma of the Anal Canal

2021 ◽  
pp. 1-5
Author(s):  
Abraão Dornellas ◽  
Abraão Dornellas ◽  
Renata C. Bonadio ◽  
Priscila M. G. Moraes ◽  
Maria I. Braghiroli ◽  
...  
Keyword(s):  
Adverse Events ◽  
Cox Regression ◽  
Negative Impact ◽  
Multivariable Analysis ◽  
Treatment Strategies ◽  
Complete Response ◽  
Median Number ◽  
Rank Test ◽  
Hiv Positive ◽  
Serious Adverse Events

Introduction: Anal cancer is a rare disease, and there is a lack of phase 3 studies in the advanced setting. Currently, the standard treatment is based on interAACT phase 2 study using Carboplatin (C) (AUC 5, D1q28) plus Paclitaxel (P) (80 mg/m2, D1,8,15q28). This study demonstrated a median OS of 20m, a response rate of 59% and serious adverse events in 36% of patients (pts). However, this regimen requires more infusions and hospital visits than a 3-weekly CP regimen, resulting in high social and financial cost. Objective: To retrospectively access safety and efficacy of treatment with 3-weekly CP in advanced SCCA. Methods: We performed a single-center retrospective analysis of patients (pts) who received first-line treatment with 3-weekly CP for inoperable locally recurrent or metastatic SCCA between Jun/2011 and Jun/2018. Study data were collected using REDCap®. Survival analyses were estimated with the Kaplan-Meier method and compared by log-rank test. Prognostic factors were evaluated by Cox regression. Results: 47 patients were included. Median age was 57 years, 60% (n=28) were female and 21% (n=10) HIV positive.16% (n=7) had metastatic disease at diagnosis. The majority of pts (n=42) were treated with paclitaxel (P) 175 mg/m2 plus carboplatin (C) AUC 5 every 3 weeks. The median number of cycles was 4 and dose reduction by toxicity was necessary for 30% (n=14). Grade 3/4 adverse events were neutropenia 19% (n=9), anemia 4% (n=2), fatigue 4% (n=2), neuropathy 2% (n=1). Two pts had interruption due to toxicity and no treatment-related death. 64% of patients benefited from treatment, 4% with complete response. The median overall survival (OS) was 10 months(m). In a multivariable analysis, HIV-positive (HIV+) status (HR 3.1; 95%CI 1.8-8.4; p 0.001) and ECOG 2/3 (HR 3.9; 95%CI 1.2-8.1; p 0.01) showed a negative impact on OS. Median OS was 16m for HIV- vs 4m for HIV+ group; and 20m for ECOG 0/1 vs 4m for ECOG 2/3. Conclusion: The present study suggests that 3-weekly CP has similar outcomes to the InterAACT regimen. Nevertheless, pts who are HIV+ or have ECOG 2/3 had poor outcomes and other treatment strategies should be studied for these pts.

A randomized phase II trial with gemcitabine with or without pertuzumab (rhuMAb 2C4) in platinum-resistant ovarian cancer (OC): Preliminary safety data

2006 ◽  
Vol 24 (18_suppl) ◽  
pp. 13001-13001 ◽  
Author(s):  
D. Glenn ◽  
F. Ueland ◽  
A. Bicher ◽  
D. Dizon ◽  
M. Gold ◽  
...  
Keyword(s):  
Adverse Events ◽  
Controlled Trial ◽  
Single Agent ◽  
Safety Data ◽  
Study Drug ◽  
Hematological Toxicity ◽  
Serious Adverse Events ◽  
Platinum Resistant ◽  
Platinum Based Chemotherapy ◽  
Grade 3

13001 Background: Pertuzumab (P), a humanized HER2 antibody, represents a new class of targeted agents called HER dimerization inhibitors (HDIs). P inhibits dimerization of HER2 with EGFR, HER3 and HER4, and subsequently inhibits signaling through MAP and PI3 kinases. Single agent P has demonstrated clinical benefit in advanced OC (ASCO 2005 abstract #5051). Methods: 40 pts with platinum-resistant OC (progressed within 6 months of receiving a platinum-based chemotherapy) were enrolled in this 1:1 randomized, double blind, placebo controlled trial of gemcitabine with or without P. Gemcitabine was administered IV on day 1 and 8 at 800 mg/m2 of a 21 day cycle. Blinded placebo or 420 mg P was administered IV on day 1. Gemcitabine was dose reduced for neutropenia or thrombocytopenia. P was not dose reduced. Results: 40 pts have been enrolled and treated with at least 1 cycle of gemcitabine in combination with blinded study drug. The median age was 58.5 (range 18–82); 26 had PS ECOG 0, 13 ECOG 1, 1 ECOG 2. The most common grade 3/4 events were neutropenia in 7 pts (17.5%), thrombocytopenia in 6 pts (15%), small bowel obstruction in 4 pts (10%), constipation in 3 pts (7.5%) and elevated ALT in 3 pts (7.4%). There was one grade 3 diarrhea, but no grade 3 or 4 rash. There were 4 serious adverse events (SAEs) attributed to study drug. These were a pleural effusion, thrombocytopenia, febrile neutropenia, and a deep vein thrombosis. Nine pts required one or two dose reductions of gemcitabine for hematological toxicity. Of 29 pts with post-baseline echo or MUGA values obtained, no pt had LVEF drop to <50%. The adverse events evaluated after 40 pts did not meet the prespecified criteria to call for an independent safety monitoring board evaluation of unblinded data. Conclusions: Preliminary safety data indicate that pertuzumab or placebo combined with gemcitabine is well tolerated with no unexpected additive toxicity. The nature and frequency of the adverse events are similar to what has been observed with either single agent gemcitabine or P. Updated data will be presented at ASCO. [Table: see text]

Subcutaneous alemtuzumab in patients with refractory/relapsed B-CLL after a fludarabine-based regimen

2006 ◽  
Vol 24 (18_suppl) ◽  
pp. 6600-6600
Author(s):  
R. Bezares ◽  
G. Stemmelin ◽  
D. Argentieri ◽  
E. Lanari ◽  
E. Guy-Garay ◽  
...  
Keyword(s):  
Interim Analysis ◽  
Residual Disease ◽  
Single Agent ◽  
Complete Response ◽  
Median Number ◽  
Duration Of Treatment ◽  
Barr Virus ◽  
Epstein Barr ◽  
Grade 3 ◽  
Cmv Disease

6600 Background: Alemtuzumab is the only immunotherapy that is effective as a single agent in patients with B-CLL who are refractory to, or who have relapsed after, fludarabine therapy. The optimized schedule for alemtuzumab that achieves maximal efficacy with manageable toxicity is still being explored. We report the first interim analysis of a new, less intensive schedule of alemtuzumab SC to patients with refractory/relapsed B-CLL. Methods: Alemtuzumab was dose escalated from 10 to 20 mg during the first week, 30 mg bid during the second and third weeks, and 30 mg once weekly during weeks 4, 6, 8, 10, 12, 16, 20, 24, 28, 34, and 40. Antiviral prophylaxis included TMP/SMX bid 3 times a week and acyclovir 200 mg tid. Results: Patients (N = 36) with refractory (19%) or relapsed (81%) B-CLL had a median age of 67 years (range, 43–86 years), 28 were male, 61%/39% had Binet stage B/C disease, and 2 had B-cell prolymphocytic transformation. The median number of prior therapies was 1 (range, 1–4). The median duration of treatment was 7 weeks (range, 2–24 weeks), with a median cumulative alemtuzumab dose of 412 mg (range, 150–1,080 mg). Thirty-two patients were evaluable for response. The overall response rate of 93%: complete response (CR), 34%; unconfirmed CR, 6%; partial response (PR), 53%. Two patients (7%) did not respond to therapy. Of the 7 refractory patients, 5 had a PR, 1 did not respond, and 1 was not yet evaluable. Median overall survival was 10 months, which correlated with response and pretreatment status. Minimal residual disease (MRD) was measured by flow cytometry in 5 patients who achieved a CR: 3 patients had <0.5% of CD5/CD19/CD23+ cells, 1 patient had <5% of CLL cells, and 1 patient had <10% CLL cells. According to WHO toxicity criteria, 5 patients experienced grade 3/4 infection; 2 patients had grade 3 granulocytopenia/thrombocytopenia; 1 patient had cytomegalovirus (CMV) reactivation without CMV disease; and 1 patient developed Epstein-Barr Virus with prolonged bone marrow hypoplasia. Conclusions: Results of this interim analysis suggest that a less intense regimen of alemtuzumab is feasible, effective, and safe for patients with refractory/relapse B-CLL after fludarabine therapy. No significant financial relationships to disclose.

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