Efficacy of Risk Adapted Cyclophosphamide, Thalidomide and Dexamethasone in Systemic AL Amyloidosis.

Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 3496-3496
Author(s):  
Ashutosh D. Wechalekar ◽  
Hugh J.B. Goodman ◽  
Julian D. Gillmore ◽  
Helen J. Lachmann ◽  
Mark Offer ◽  
...  
Keyword(s):  
Heart Failure ◽  
Dose Reduction ◽  
Survival Data ◽  
Standard Dose ◽  
Single Agent ◽  
Response Rates ◽  
Complete Response ◽  
Median Number ◽  
Al Amyloidosis ◽  
Starting Dose

Abstract The prognosis for advanced AL amyloidosis (AL) with conventional treatment remains very poor and stem cell transplantation has unacceptably high mortality (TRM). Single agent thalidomide in standard doses is poorly toleranated and has low response rates in AL (Dispenzieri et al, Amyloid10:247; 2003) and few data on the role of thalidomide based combination chemotherapy in AL are available. We report experience with a risk adapted thalidomide based combination using cyclophosphamide and dexamethasone (CTD) in 43 patients with AL amyloidosis at the National Amyloidosis Centre, UK. The regime (adapted from the UK MRC Myeloma IX trial) consisted of a 21-day cycle oral cyclophosphamide 500mg once weekly, thalidomide 200mg/day (starting dose 100mg/day, increased after 4 weeks if tolerated) continuously and dexamethasone 40mg days 1–4 and 9–12. This was risk attenuated (CTDa) in the elderly (>70yrs), heart failure >NYHA grade II or significant fluid overload to a 28-day cycle of cyclophosphamide 500mg days 1, 8 and 15, thalidomide 200mg/day (starting dose 50mg/day, 4–weekly 50mg increments as tolerated), and dexamethasone 20mg day 1–4 and 15–18. A total on 43 patients (22M:21F, median age 61yrs, range 43–79) were treated; 35 received CTD and 8 received CTDa. Median number of organs involved was 2 (1–4), including renal in 62% of patients, cardiac in 60%, hepatic in 39%. Median follow-up from treatment initiation was 7mo (0.4–35) and from diagnosis 16.5mo (0.6–69). Patients received a median of 4 cycles of treatment (1–7). The number of previous treatments was none in 39%, one in 39%, two in 14% and three in 6%. Toxicities were seen in 17 (39%) of patients (CTDa 3; CDT 14) necessitating dose reduction in 11 (25%), dexamethasone omission in 6 (14%), thalidomide omission in 1 (2%) and complete regime discontinuation in 4 (9%). The main side effects were: worsening heart failure 20%, neuropathy 11%, infections 11%, sleepiness 2%, and neutropenia, renal impairment, constipation and fatigue − 4% each with no thrombotic complications or TRM. Survival data was evaluable in all patients while response was evaluable in 35 (81%).Haematologic response was defined as follows: complete response (CR) - sustained normalisation of sFLC (serum free light chains) ratio, partial response (PR) - sustained ≥50% reduction in pre-treatment clonal isotype. There was a haematologic response in 26 (74%). 12 (34%) has a CR, 14 (40%) had a PR, 9 (25%) had no response. sFLC assays were available after every cycle in 27pts; a reduction in the clonal class of ≥25% was evident within 30days in 59% and in another 33% by day 60. An appreciable regression of amyloid was evident in 15% of the responders by SAP scintigraphy. The median survival for the cohort has not been reached at 36 months. This preliminary study shows excellent efficacy of CTD in patients with advanced AL with response rates superior to conventional intermediate dose chemotherapy. The regime appears to be safe with no treatment related mortality and tolerance appears to be better than than standard dose thalidomide alone (Dispenzieri et al, Amyloid10:247; 2003) or with dexamethasone (Pallidini et al, Blood105:7;2005). However, a quarter of the patients needed dose reduction and more stringent use of risk adaptation may improve the tolerability of this regime. Risk adapted CTD may be an alternative to standard therapies as front line treatment in AL amyloidosis.

Venetoclax induces sustained complete responses in refractory/relapsed patients with cardiac AL amyloidosis.

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. e19538-e19538 ◽  
Author(s):  
Fabien Le Bras ◽  
Jehan Dupuis ◽  
François Lemonnier ◽  
Silvia Oghina ◽  
Diane Bodez ◽  
...  
Keyword(s):  
Therapeutic Option ◽  
Influenza Infection ◽  
Single Agent ◽  
Complete Response ◽  
Median Number ◽  
Al Amyloidosis ◽  
Duration Of Treatment ◽  
Systemic Involvement ◽  
Academic Center ◽  
Heavily Pretreated

e19538 Background: Venetoclax (VEN) is an orally bioavailable small molecule inhibitor of the anti-apoptotic protein BCL-2 and has been shown to have efficacy against myeloma (MM), particularly in patients that harbor t(11;14). Approximately, 50% of AL amyloidosis patients will exhibit t(11;14) making VEN an attractive therapeutic option. Methods: We here report the results of a retrospective analysis of a monocentric series of refractory/relapsed (R/R) patients (pts) heavily pretreated with cardiac AL amyloidosis treated in a french academic center. VEN was given daily alone or in association with dexamethasone (DEX), with or without bortezomib (BTZ). Treatment was planned to be administered until progression. Results: Between February 2017 and January 2019, 7 consecutive R/R pts have been treated. All had received previous BTZ and daratumumab (DARA) containing regimen. Baseline characteristics were: median age: 72.7 years (range 40-84), Mayo Clinic stage: stage I in 2 pts, stage II in 3 and stage IIIA in 2. All patients but one had in addition to cardiac deposit, systemic involvement including kidney, joint, neurologic, gastro-intestinal tract, lymph node and muscle. All but one pts were refractory to their last treatment consisting of DARA-DEX with or without IMID. The t(11;14) translocation was present in 5 pts, absent in 1 and undetermined in 1 pts. Two pts had concomitant MM at diagnosis. Median number of previous line treatments was 4 (3-5). Five patients received VEN- BTZ- DEX as described in MM (PMID: 28847998), 1 with DEX and 1 as monotherapy. Five pts received 400 mg/d, one 200 mg/d and one 100 mg/d. Median duration of treatment was 76 days (30-713). All patients but one are still on treatment. One patient treated with 400 mg/d had a dose reduction to 100 mg/d due to grade 2 diarrhea. Four patients received at least 2 cycles and were evaluable for response. One 84 y old patient in stable disease after 1 cycle died due to influenza infection. 2 patients received only one cycle of treatment. Hematological complete response occurred in 2/4 (50%) patients, after 63 and 27 days. Interestingly, responses were sustained as the 2 responders were still on therapy after 76 and 713 days. This later patient, refractory to 2 previous lines had a cardiac and neurologic response. The 2 responding patients had proven t(11:14). Conclusions: On this limited series of heavily pretreated patients with R/R AL cardiac amyloidosis VEN used as a single agent or in combination can induce prolonged response and seems a promising drug with an acceptable safety profile in patients with t(11;14).

FCR-3 as Frontline Therapy for Patients with Chronic Lymphocytic Leukemia (CLL).

Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 2117-2117 ◽  
Author(s):  
Susan O’Brien ◽  
William G. Wierda ◽  
Stefan Faderl ◽  
Alessandra Ferrajoli ◽  
Carlos E. Bueso-Ramos ◽  
...  
Keyword(s):  
Somatic Hypermutation ◽  
Single Agent ◽  
Response Rates ◽  
Median Number ◽  
Lymphocytic Leukemia ◽  
Combination Regimen ◽  
Consensus Primer ◽  
Dose Dense ◽  
Wbc Count

Abstract The combination regimen of Fludarabine, Cyclophosphamide, and Rituximab (FCR) has produced high overall response (OR) rates and complete remission (CR) rates in patients receiving this as initial treatment for CLL. Earlier studies have shown that dose-dense or dose-intensified regimens of single-agent Rituximab produced higher response rates in patients with CLL. The current regimen, FCR-3, was based on the hypothesis that increasing the amount of Rituximab in the combination might improve response rates and remission duration. Doses of chemotherapy were Fludarabine 25 mg/m2/Dx3, and Cyclophosphamide 250 mg/m2/Dx3 given monthly. Rituximab was given at 375 mg/m2 as the first dose and 500 mg/m2 for all subsequent doses. On each day of the chemotherapy a dose of Rituximab was given so 3 doses were given monthly. With the previous FCR regimen 45% of patients achieved a CR or nPR and had <5% CD19+ 5 positive cells in the marrow at the completion of 3 cycles of therapy (rapid response, RR). The median time to progression (TTP) in that group has not been reached; it was 3 years in patients who did not achieve that endpoint (p<.001). The current protocol aimed to increase that response rate from 45% to 60%. Sixty-five patients were treated. Eighty percent were men. The median age was 59 years (27–82). Rai Stage 3–4 disease was present in 25% of patients. Median WBC count was 92.4 x 103/ul (7.9–363). Median B2-microglobulin was 3.8 (1.6–10.1). Unfavorable FISH abnormalities were present in 35% of 52 evaluable patients. Somatic hypermutation status was available for 44 patients; 61% were unmutated. ZAP-70 expression analysis performed by immunostaining or flow cytometry was positive in 62% of 47 evaluable patients. Results of FCR-3 in comparison to FCR are shown in the table. 3 Cycles 6 Cycles No. RR(%) OR CR Flow<5% FCR 300 45 95 72 82 FCR-3 65 45 94 65 74 PCR negativity using consensus primer PCR was achieved in 49% of patients at the end of therapy. Median number of days between courses ranges from 29–35 per course (overall range 27–95). Eighty-five percent of patients completed 6 cycles. No patient has progressed with a median follow-up of 10 months. With limited follow-up the addition of 3 doses of Rituximab to FC chemotherapy does not appear to provide greater benefit than one dose.

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

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

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

A Phase I/II Trial of Ixazomib (Ix), Pomalidomide (POM), and Dexamethasone (DEX), in Relapsed/Refractory (R/R) Multiple Myeloma (MM) Patients: Responses in Double/Triple Refractory Myeloma and Poor Risk Cytogenetics

Blood ◽  
2016 ◽  
Vol 128 (22) ◽  
pp. 3316-3316 ◽  
Author(s):  
Amrita Krishnan ◽  
Prashant Kapoor ◽  
Joycelynne Palmer ◽  
Ni-Chun Tsai ◽  
Shaji Kumar ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
High Risk ◽  
Phase I ◽  
Research Funding ◽  
Standard Dose ◽  
Single Agent ◽  
Median Number ◽  
Maximum Tolerated Dose ◽  
Refractory Disease ◽  
Poor Risk

Abstract Triplet regimens combining an immunomodulatory agent, a proteasome inhibitor (PI), and a steroid are used to treat newly diagnosed and relapsed multiple myeloma (MM). Although ixazomib (Ix), an oral PI with single agent activity, can be combined with lenalidomide (LEN), patients (pts) with relapsed/refractory (R/R) MM are often LEN-refractory. Pomalidomide (POM) has single agent activity in LEN-refractory disease, and both POM and Ix also show activity in poor cytogenetic risk pts. Methods: Primary objectives: 1) determine the maximum tolerated dose (MTD) of Ix in combination with standard dose POM and dexamethasone (DEX), and 2) evaluate the anti-tumor activity of the triplet. The treatment regimen included two dose levels (3 mg and 4 mg) of Ix on days 1, 8, 15; POM 4 mg days 1-21; and DEX 40 mg days 1, 8, 15, 22, of a 28 day cycle. Eligibility: R/R MM after >1 prior therapy, LEN-refractory, and ≤ grade(gr) 1 peripheral neuropathy (PN). Pts were treated until progression or unacceptable toxicity. Design: Phase I study utilizing a standard 3+3 design; dose limiting toxicities (DLTs) defined during cycle 1. Results: 32 pts treated, 31 evaluable for toxicity and response. Pts received a median 4 cycles (range 1-13); median follow-up is 5.5 months (range 1.8-21.1). Six pts treated on DL1, 25 treated on DL2, the MTD/Phase II dose (P2D). Median age: 62 years (range 38-84); median time from diagnosis: 3.7 years (range 1.0-8.9); median number prior therapies: 3 (range 1-5); prior transplant: n = 23 (74%); double (LEN/Bortezomib[BOR]) or triple (LEN/BOR/Carfilzomib[CFZ]) refractory: 19 (61%). Phase I: DL1 expanded to n=6 after 1/3 pts experienced DLT (gr3 lung infection); no further DLT seen on DL 1 or 2. Adverse events (AEs) related to POM and/or Ix: ANC decrease Gr1/2 n=11 (35%), Gr3/4 n=10 (32%), platelet decrease Gr1/2 n=9 (29%), lymphocyte decrease Gr1/2 n=8 (26%), Gr3/4 n=11 (35%), PN Gr1/2 n=9 (29%), no Gr3/4. Response: Phase I and II, n=31 pts treated. ORR: 45% (6 VGPR, 8 PR); Clinical Benefit Rate (CBR): 81% (6 VGPR, 8 PR, 3 MR, 8 SD). In the pts with high risk cytogenetics (7[23%] 1q, 3[10%] 17p, 2[6%] t(4;14)) an ORR of 58% (3 VGPR, 4 PR) was seen, and the CBR was 83%. In the double or triple refractory pts, an ORR of 26% and CBR of 79% (1 VGPR, 4 PR, 3 MR, 7 SD) were observed. Conclusions: Ix/POM/DEX is a well-tolerated oral combination therapy, and responses were seen even at DL1 and in high risk patients, including those with poor-risk cytogenetics or advanced refractory disease. Disclosures Kapoor: Celgene: Research Funding; Amgen: Research Funding; Takeda: Research Funding. Kumar:Millennium: Consultancy, Research Funding; AbbVie: Research Funding; Glycomimetics: Consultancy; Sanofi: Consultancy, Research Funding; Noxxon Pharma: Consultancy, Research Funding; Celgene: Consultancy, Research Funding; BMS: Consultancy; Kesios: Consultancy; Onyx: Consultancy, Research Funding; Skyline: Honoraria, Membership on an entity's Board of Directors or advisory committees; Janssen: Consultancy, Research Funding; Array BioPharma: Consultancy, Research Funding. Lonial:Novartis: Consultancy; BMS: Consultancy; Janssen: Consultancy; Merck: Consultancy; Celgene: Consultancy; Onyx: Consultancy; Novartis: Consultancy; BMS: Consultancy; Celgene: Consultancy; Millenium: Consultancy; Janssen: Consultancy; Onyx: Consultancy. Nathwani:Carevive Systems, Inc.: Research Funding. Forman:Mustang Therpapeutics: Other: Construct licensed by City of Hope. Berdeja:Abbvie, Acetylon, Amgen, Bluebird, BMS, Calithera, Celgene, Constellation, Curis, Epizyme, Janssen, Karyopharm, Kesios, Novartis, Onyx, Takeda, Tragara: Research Funding.

Prospective comparison of subcutaneous to intravenous administration of bortezomib in patients with multiple myeloma: Pharmacokinetics, efficacy and toxicity

2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 8046-8046 ◽  
Author(s):  
P. Moreau ◽  
V. Coiteux ◽  
C. Hulin ◽  
T. Facon ◽  
H. van de Velde ◽  
...  
Keyword(s):  
Standard Dose ◽  
Area Under The Curve ◽  
Proteasome Inhibition ◽  
Response Rates ◽  
Median Number ◽  
Route Of Administration ◽  
Systemic Availability ◽  
Local Tolerability ◽  
Local Tolerance ◽  
Prospective Comparison

8046 Bortezomib (Bz) is a novel proteasome inhibitor that is registered for treatment of relapsed or refractory MM as an IV bolus injection. Animal toxicology studies have indicated good local tolerability and an acceptable PK profile of SC injection of Bz supporting together with preliminary clinical data the exploration of this route of administration in humans. We conducted a randomized trial to compare pharmacokinetics/pharmacodynamics (PK/PD), toxicity and efficacy of SC and IV injections of Bz, both at standard dose of 1.3 mg/m2 twice weekly for 2 wks (day 1–4-8–11), with 1 wk rest, for up to 8 cycles. From 01/06 to 10/06, 24 pts with relapsed/refractory MM were randomized to receive Bz either IV (arm A, n = 12) or SC (arm B, n = 12); Patients received a median number of 5 cycles in both groups. The local tolerance of SC injections was good. Response rates were similar in both groups (CR+VGPR/PR/MR: 3/2/1 in arm A, vs 3/2/2 patients in arm B. Grade 3 / 4 adverse events occurred in 7 cases in arm A, vs 5 in arm B, leading to study discontinuation in 5 and 3 cases, respectively. PK analysis: average plasma Cmax values were lower for SC as compared to IV (15 ng/mL at day 1, and 23 at day 11, vs 130 and 127, p < .001), but overall systemic availability as measured by plasma AUC values were comparable between SC and IV administration for both day 1 & 11 (145 and 388 ng.h/mL, vs 133 and 386, p =.7 & .98, respectively). Average Tmax values were less than 1 hour for both routes. PD analysis (20S proteasome inhibition): average area under the curve for effect (AUE) values were comparable between SC and IV administration both for day 1 & 11 (761 and 1,324 %.h, vs 1,089 and 1,110, p = .29 & .54, respectively), while average Emax values were lower for SC administration (Emax day 1 & day 11 SC, 58 and 56%, vs 72 and 69% IV, p =.003 & .01 respectively). The overall systemic availability of Bz was comparable between SC and IV administration for both day 1 and 11. Similarly, the average AUE results were comparable between SC and IV, while average Emax was lower for SC administration. Response rates were identical in the 2 groups of patients, with similar toxicity profile. Given the good local tolerance of SC injection, this route of administration could be an alternative option to IV injection. [Table: see text]

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.

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

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

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

A phase II clinical trial of ganetespib (STA-9090) in previously treated patients with advanced esophagogastric cancers.

2013 ◽  
Vol 31 (15_suppl) ◽  
pp. 4090-4090 ◽  
Author(s):  
Eunice Lee Kwak ◽  
Lipika Goyal ◽  
Thomas Adam Abrams ◽  
Amanda Carpenter ◽  
Brian M. Wolpin ◽  
...  
Keyword(s):  
Clinical Trial ◽  
Cancer Progression ◽  
Single Agent ◽  
Heat Shock Protein 90 ◽  
Complete Response ◽  
Median Number ◽  
Oncogenic Signaling ◽  
Her2 Positive ◽  
Phase 2 Trial ◽  
Ecog Ps

4090 Background: Subsets of esophagogastric (EG) cancers harbor genetic abnormalities, including amplification of HER2 or MET, or mutations in PIK3CA, EGFR, or BRAF. These genes encode clients of the molecular chaperone heat-shock protein 90 (HSP90), and inhibition of HSP90 may promote the degradation of these oncogenic signaling proteins. Ganetespib is a novel triazolone heterocyclic inhibitor of HSP90 that is a biologically rational treatment strategy for advanced EG cancers. Methods: This was a multicenter, single-arm Phase 2 trial. Eligibility: Histologically confirmed advanced EG cancer; progression on ≤ 2 lines of systemic therapy; ECOG PS 0-1. Treatment: Ganetespib 200mg/m2IV on Days 1, 8, and 15 of a 28-day cycle. Primary endpoint: overall response rate (ORR). Results: 26/28 patients enrolled received ≥ 1 dose of drug. The characteristics of the 26 patients were: male 77%, median age 64 years old; ECOG PS 0/1 42/58%; median number of prior therapies 2; esophageal/GEJ/gastric 27/42/31%; prior platinum 92%, prior fluoropyrimidine 88%, prior taxane 38%, prior trastuzumab 15%. Median follow-up was 83 days. The most common drug-related adverse events were: diarrhea (77%), fatigue (65%), elevated ALKP (42%), and elevated AST (38%). The most common Grade 3/4 AEs included: leucopenia (12%), fatigue (12%), diarrhea (8%), and elevated ALKP (8%). 14/26 required ≥ 1 dose modification. 22/26 patients completed at least 2 cycles of ganetespib and were evaluable for response. One complete response was seen, and this patient continues on treatment as of cycle 31 (27.5 mos). Molecular characterization of this patient’s tumor revealed a KRAS mutation in codon 12. The ORR was 1/26 (4%). Two of six patients with HER2-positive disease achieved 12% and 19% tumor reduction from baseline, respectively. TTP was 48 days (1.6 mos) and OS was 83 days (2.8 mos). Conclusions: Ganetespib showed manageable toxicity. While the study was terminated early due to insufficient evidence of single agent activity, the durable CR and 2 minor responses suggest that there may be a subset of EG patients who could benefit from this drug. The molecular determinants of response, however, have yet to be fully characterized. Clinical trial information: CT01167114.

Nivolumab in renal cancer: French evaluation of use, current practices and medico economic approach.

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. e16093-e16093
Author(s):  
Francoise Grude ◽  
Gildas Appéré ◽  
Fanny Marhuenda ◽  
Delphine Deniel Lagadec ◽  
Elouen Boughalem ◽  
...  
Keyword(s):  
Survival Data ◽  
Renal Carcinoma ◽  
Real Life ◽  
Progression Free Survival ◽  
Complete Response ◽  
Median Number ◽  
Real Life Setting ◽  
Medico Economic ◽  
Ecog Ps ◽  
Grade Iii

e16093 Background: Since April 2016 (EMA approval), Nivolumab could be prescribed in advanced renal carcinoma after prior treatment. The Brittany and Pays de la Loire Cancer Observatory has collected data on their real-life indications, current management, safety, efficacy and medico-economics. Methods: All non opposing adult patients with renal carcinoma initiated nivolumab (3 mg/kg q2w) in 2016 and 2017 were included. Minimum follow-up for survival was 12 months. Sex, age, performans status PS ECOG, toxicities, response rate, Progression Free Survival (PFS) and Overall Survival (OS) have been studied. Results: 141 pts were treated by nivolumab in 2016 and 2017 with a median age of 68 years old [39-94] and with 26% aged at least 75 years. The median number of courses was 7 [1-47]. 68 pts (48%) had 1 to 6 courses, 16 pts (11%) 7 to 12 courses, 25 pts (18%) 13 to 24 courses and 32 pts (23%) more than 25 courses. 81 (58%) pts were treated in 2nd line, 34 (24%) in 3rd line, and 25 (18%) in further lines. All lines combined, Complete Response (CR) was observed for 3 pts (2%), Partial Response (PR) for 26 pts (18%), Stable Disease (SD) for 36 pts (26%) (disease control DC : 46%) and disease progression for 51 pts (36%). For 25 pts (18%), nivolumab treatment has been stopped before first medical imaging. PS ECOG was 0-1 for 88 pts (62%), 2 for 21pts (15%), 3-4 for 8 pts (6%) and unknown for 24 pts. Median OS and PFS were 18.2 months and 3.2 months, respectively. No difference on survival has been noticed according to gender, treatment line, age (cut-off 70 or 75 yo) and grade III/IV toxicity. However, OS and PFS were significantly influenced by general health (p < 0.0001). PFS for PS 0-1 pts was 6.5 months, for PS2 2.3 months and for PS3-4 0.8 months. OS was not reached for PS0-1 pts, 3.8 months for PS2 pts and 0.8 months for PS3-4 pts. OS for patients with DC (RC+RP+SD) has not reached and PFS was 14.9 months respectively. 17% of patients presented grade III/IV toxicities. Nivolumab courses during the 2 years costed 5.1 millions of euros (drug, hospitalisation and transportation). 80% of this costs were dedicated to pts who experienced DC. Conclusions: In real life setting, survival outcomes and toxicities with nivolumab in advanced renal carcinoma are comparable to literature’s data. ECOG PS≥2 pts presented shorter survival than PS0-1 pts. Interestingly, 80% of the cost incurred for these treatments benefited to pts with DC. Updated survival data will be available be shown at the meeting.

Lenalidomide and dexamethasone in the treatment of AL amyloidosis: results of a phase 2 trial

Blood ◽  
2006 ◽  
Vol 109 (2) ◽  
pp. 492-496 ◽  
Author(s):  
Vaishali Sanchorawala ◽  
Daniel G. Wright ◽  
Michael Rosenzweig ◽  
Kathleen T. Finn ◽  
Salli Fennessey ◽  
...  
Keyword(s):  
Single Agent ◽  
Complete Response ◽  
Plasma Cell Dyscrasia ◽  
Al Amyloidosis ◽  
Phase 2 ◽  
Immunoglobulin Light Chain ◽  
Treatment Regimens ◽  
Hematologic Response ◽  
Phase 2 Trial ◽  
Clinical Responses

AbstractIn immunoglobulin light chain (AL) amyloidosis, amyloid fibril deposits derived from immunoglobulin light chains produced by a clonal plasma cell dyscrasia accumulate in tissues and damage vital organs. Treatment regimens used in multiple myeloma can be effective in AL amyloidosis; however, patients with this disease often tolerate these regimens poorly because of multisystem organ dysfunction. Thalidomide and lenalidomide have both been shown to be effective in myeloma. In this report, we describe results of a phase 2 trial of the use of lenalidomide, as a single agent and in combination with dexamethasone, for the treatment of AL amyloidosis. Thirty-four patients with AL amyloidosis, most with prior therapies, were enrolled in the trial. The initial dose of lenalidomide used (25 mg/d) was poorly tolerated; however, a reduced dose of 15 mg/d was generally well tolerated. Of 24 evaluable patients, 7 (29%) achieved a hematologic complete response and 9 (38%) achieved a partial hematologic response, for an overall hematologic response rate of 67%. Hematologic responses were also associated with clinical responses. Fatigue and myelosuppression were the most common treatment-related adverse events (35%), while thromboembolic complications (9%) were the most serious. Findings from this trial indicate that lenalidomide can be effective in treating AL amyloidosis.

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