Venetoclax 400mg Combined with Bortezomib and Dexamethasone Is Efficacious and Feasible for Plasma Cell Dyscrasia

Abstract 【Abstract】 Objective: To investigate the efficacy and safety of BCL-2 inhibitor Venetoclax (Ven) 400mg combined with bortezomib and dexamethasone in plasma cell dyscrasia with t(11,14). Methods: The data of twenty patients with plasma cell dyscrasia with t (11;14) were retrospectively analyzed.The majority of patients received Venetoclax 400mg combined with bortezomib and dexamethasone. The baseline clinical information, treatment efficacy and adverse effects after Ven-based regimen. Results: Seventeen multiple myeloma patients, two light-chain amyloidosis and one primary plasma cell leukemia (pPCL) patients were studied. Among seventeen MM patients, the median follow-up was 9.0 (0.5-27) months and the median treatment cycles was 4 (1-12);fourteen patients have been evaluated for response rate. The overall response rate for evaluable patients (ORR) was 85.7%, among that one patient (7.1%) achieved CR, four patients (28.6%) achieved VGPR and 7 (50%) achieved PR. The median progression-free survival (PFS) was11.0 months (95%CI 2.1-19.9); the median Overall survival (OS) was 14.0 months (95%CI 6.9-21.1). Two amyloidosis patients achieved VGPR and PR respectively, while one pPCL patient achieved CR. The most common grade 3 or worse treatment-emergent adverse events were thrombocytopenia (15%), infection (10%), neutropenia (5%), diarrhea (5%) and peripheral neuropathy (5%). There was no treatment-related death. Conclusion Ven (400mg) combined with bortezomib and dexamethasone is feasible, tolerated and efficacious in plasma cell dyscrasia. 【Key words】Plasma cell dyscrasia; Venetoclax; Efficacy; Safety Disclosures No relevant conflicts of interest to declare.

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Primary Plasma Cell Leukemia: Results of a Retrospective Italian Multicentric Survey.

Blood ◽

10.1182/blood.v114.22.2885.2885 ◽

2009 ◽

Vol 114 (22) ◽

pp. 2885-2885

Author(s):

Livio Pagano ◽

Caterina Giovanna Valentini ◽

Valerio De Stefano ◽

Adriano Venditti ◽

Giuseppe Visani ◽

...

Keyword(s):

Plasma Cell ◽

Response Rate ◽

Conflicts Of Interest ◽

Alkylating Agents ◽

Plasma Cell Leukemia ◽

High Dose ◽

Cell Leukemia ◽

Front Line ◽

Line Therapy ◽

Primary Plasma Cell Leukemia

Abstract Abstract 2885 Poster Board II-861 Background: Epidemiological and clinical information on Primary Plasma Cell Leukemia (pPCL) are rarely reported. Aims: To evaluate in patients (pts) with pPCL the clinical features, the prognostic factors, and the efficacy of treatments. Patients and Methods: A multicenter retrospective cohort study was carried out between January 2000 and December 2008 in 26 Italian hematology divisions. A total of 128 cases of PCL were collected, and 73 of them (57%) were classified as primary (M/F 43/30). Results: The median age was 63 years (range 32-86). At diagnosis the median values of peripheral blood plasma cells and bone marrow plasma cell infiltration were 2.7 × 10 9/L (range 0.4-49.9) and 80% (range 37-100), respectively. The median values of hemoglobin, white blood cell count, and platelet counts were 9.1 g/dl (range 4.8-12.9), 13.7 × 10 9/L (range 1.3-56.7), 116 × 10 9/L (range 8-428), respectively. Extramedullary disease was present in ten cases (14%) and included testis, muscular, neuromeningeal, and cutaneous localization. At diagnosis, 64 pts (88%) had at least one CRAB sign, namely 35 pts (48%) had low hemoglobin level, 20 pts (27%) calcium ≥11 mg/dl, 32 pts (44%) creatinine ≥2 mg/dl, and 47 pts (64%) had osteolysis. In 41 pts (56%) cytogenetic study was performed, revealing an unfavourable karyotype in 17 (23%), in 13 of them del(13q-). Seventy-two pts received front-line therapy (1 died early, receiving only support treatments and steroids), that included antracycline-containing regimens in 36 pts (50%), and single alkylating agents in 17 pts (24%, 9 cyclofosfamide and 8 melphalan). In 11 of them Bortezomib (BTZ, n= 7) or Thalidomide (THAL, n= 4) were also employed. Finally, 19 pts (26%) received BTZ (4) or THAL (5) or both (10) as unique treatment. Twenty-one pts (29%) underwent autologous stem cell transplantation (SCT) as part of front-line therapy, followed by allogeneic-SCT in four cases; two additional pts underwent only allogeneic-SCT. A complete or partial remission after front-line therapy was achieved in 20 pts (27%) and 19 pts (26%) respectively (overall response rate 53%). The median overall survival (OS) was 13.1 months (range 0.5-75.8); 30.6 months (range 4.7-75.8) in responder pts and 4.2 months in non-responder ones (range 0.5-75.6, univariable hazard ratio, HR, 0.28, 95% CI 0.11-0.39). In the responder pts the median progression free survival (PFS) was 17.2 months (range 1.4-72.1). Of note, in SCT pts the median OS and PFS were 38.1 months (range 4.8-75.8) and 25.8 months (range 1.4-72.1) respectively, with a significant advantage with respect to non-transplanted pts in OS (median 9.1 months, range 0.5-75.6, HR 0.28, 95% CI 0.16-0.52) and in PFS (median 7.3 months, range 1.7-17.7, HR 0.29, 95% CI 0.04-0.44). The low number of allo-SCTs did not allow a reliable separate statistical analysis. A multivariable Cox proportional hazard regression analysis showed that OS was influenced by lack of initial response (HR 2.62, 95% CI 1.04-6.57), albumin <3 g/dl (HR 3.33, 95% CI 1.64-6.76), and SCT (HR 0.34, 95% CI 0.12-0.98). Pts with hypercalcemia at diagnosis had a shorter PFS (HR 4.0, 95% CI 1.04-15.24); the PFS was favourably influenced by SCT (HR 0.05, 95% CI 0.009-0.28). Overall, the use of BTZ and/or THAL did not influence the OS and PFS. Conclusions: pPCL is a highly aggressive lymphoprolipherative malignancy, characterized by a poor prognosis and a low response rate to conventional therapy. The use of high-dose chemotherapy followed by autologous or allogeneic-SCT is a very effective therapy leading to 66% increase in the OS and to 95% increase in PFS in respect to non-transplanted pts. Apparently, the use of novel drugs such as BTZ and THAL did not produce a further amelioration in the patient outcome. However, those latter findings should be taken with caution, given the relatively low number of treated pts. Disclosures: No relevant conflicts of interest to declare.

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Lenalidomide and Low Dose Dexamethasone As First Line Therapy for Newly Diagnosed Patients with Primary Plasma Cell Leukemia

Blood ◽

10.1182/blood.v120.21.729.729 ◽

2012 ◽

Vol 120 (21) ◽

pp. 729-729 ◽

Cited By ~ 1

Author(s):

Pellegrino Musto ◽

Vittorio Simeon ◽

Giovanni D'Arena ◽

Maria Carmen Martorelli ◽

Maria Teresa Petrucci ◽

...

Keyword(s):

Plasma Cell ◽

Low Dose ◽

Response Rate ◽

Plasma Cell Leukemia ◽

Hematological Toxicity ◽

Cell Leukemia ◽

First Line ◽

First Line Therapy ◽

Primary Plasma Cell Leukemia ◽

Grade 3

Abstract Abstract 729 Introduction: The prognosis of primary plasma cell leukemia (PPCL) remains poor. The “novel agents” have recently shown promising results in PPCL patients in case reports or small retrospective series. Here we describe the first prospective, multicenter, phase II clinical trial of PPCL, where lenalidomide in combination with low dose dexamethasone (Ld) was tested as initial therapy in newly diagnosed patients fulfilling the IMWG diagnostic criteria of PPCL. Patients and methods: Ld regimen consisted of lenalidomide 25 mg/d for 21 days and oral dexamethasone 40 mg on days 1, 8, 15, and 22 for each 28-day cycle. After 4 cycles, responding patients not eligible for stem cell transplantation (SCT) continued until 8 cycles of full-dose Ld, followed by a maintenance dose of single agent lenalidomide equal to 10 mg/d on days 1–21 of each 28-day cycle. Patients responding after 4 cycles and eligible for SCT proceeded according to the treatment centre's transplant policy. Patients not responding after 4 cycles or progressing during this treatment were considered off-study. Appropriate dose reductions (in particular for patients with reduced renal function at baseline), double contraception methods and anti-thrombotic/anti-infective prophylaxis were recommended. The primary end-point was early response rate according to IMWG uniform response criteria. Secondary end-points were PFS, OS, feasibility and efficacy of SCT, safety. Results: According to the Simon optimal two-stage adaptive design, twenty-three patients were enrolled in between March 2009 and May 2011. The male/female ratio was 1.1, and median age was 60 years (range 44–80). The median absolute number and percentage of circulating plasma cells were 4.280/μl (range 1.500–114.660) and 34% (range 21–90) respectively. Fifteen patients (65.2%) had abnormal renal function at presentation. Twenty-one patients (91.3%) were tested by FISH analysis and cytogenetic abnormalities were detected in all of them, del13q being the most frequently found (16 patients). Seventeen patients showed multiple chromosomal lesions. Involvement of chromosome 14 was observed in 18 patients, three of whom showed t(4;14). Chromosome 1q gain and del17p were detected in 10 and 7 patients, respectively. In the intention-to-treat (ITT) population, overall response rate (ORR) after at least one Ld cycle was 73.9% (17/23), with 8 patients (34.7%) achieving partial remission (PR), 5 (21.7%) very good PR (VGPR), 3 (13%) complete response (CR), and 1(4.3%) near CR (nCR) (VGPR or better: 39%). In the efficacy-evaluable (EE) population, 14 out of 15 patients who received the initially planned 4 Ld cycles (65.2% of the ITT population) responded (ORR 93.3%), achieving 5 PR (33.3%), 5 VGPR (33.3%), 1 near-CR (6.6%) and 3 CR (20%) (VGPR or better: 59.9%). The maintenance phase was reached and safely performed in 4 responding patients not eligible for SCT, 3 of whom relapsed after 2, 8 and 22 months, respectively. After Ld induction therapy, 8 patients received single (n. 4) or double (n. 4) autologous SCT (ASCT); another patient underwent a sequence of ASCT followed by non-myeloablative allogeneic SCT (AlloSCT). Six eligible patients did not receive ASCT frontline, due to initial Ld failure or adverse events; three of them underwent single ASCT (n. 2) or tandem ASCT/non-myeloablative AlloSCT (n. 1) after a bortezomib-based salvage therapy, achieving 2 CR and 1 PR. After a median follow-up of 23 months, median OS and PFS in ITT population were not reached and 22 months, respectively. All transplanted patients remained alive, although three of them relapsed and started salvage treatments; OS was 12 months in the 11 patients who did not receive ASCT (p < 0.001). The correspondent figures for PFS were 29 and 16 months, respectively (p < 0.01). Considering ITT population, multivariate analyses showed that SCT was positively correlated to both OS and PFS. There were 17 episodes of grade 3/4 non hematological toxicity, which occurred in 13 patients (5 infections, 3 renal, 3 metabolic, 2 gastro-intestinal, 2 skin, 1 fatigue, 1 thromboembolic), causing early interruption of Ld treatment in 4 patients. Grade 3/4 hematological toxicity (mainly neutropenia) occurred in 11 patients (47.8%). Conclusions: Ld may be a feasible and effective initial therapeutic option for PPCL, particularly in patients who receive ASCT after a short course of induction treatment. Disclosures: Musto: Celgene: Honoraria, Research Funding. Off Label Use: Lenalidomide as first line therapy of plasma cell leukemia. Petrucci:Celgene: Honoraria. Cascavilla:Celgene: Honoraria. Di Raimondo:Celgene: Honoraria. Caravita:Celgene: Honoraria. Morabito:Celgene: Honoraria. Offidani:Celgene: Honoraria. Bringhen:Celgene: Honoraria. Boccadoro:Celgene: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau. Palumbo:Celgene: Consultancy, Honoraria.

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A randomized phase II clinical trial of gemcitabine, oxaliplatin, erlotinib combination chemotherapy versus gemcitabine and erlotinib in previously untreated patients with locally advanced or metastatic pancreatic cancer.

Journal of Clinical Oncology ◽

10.1200/jco.2018.36.4_suppl.344 ◽

2018 ◽

Vol 36 (4_suppl) ◽

pp. 344-344 ◽

Cited By ~ 1

Author(s):

Sung Hee Lim ◽

Jina Yun ◽

Min-Young Lee ◽

Han Jo Kim ◽

Kyoung Ha Kim ◽

...

Keyword(s):

Pancreatic Cancer ◽

Response Rate ◽

Locally Advanced ◽

Progression Free Survival ◽

Metastatic Pancreatic Cancer ◽

Overall Response ◽

Significant Difference ◽

Common Grade ◽

Secondary Endpoints ◽

Grade 3

344 Background: Erlotinib is the only targeted agent in combination with gemcitabine showing significantly improved outcomes in pancreatic cancer. Although combining platinum agent with gemcitabine has not provided clear survival benefit over gemcitabine alone, gemcitabine plus platinum resulted in improved response rate and progression-free survival (PFS). We tried to evaluate whether the addition of oxaliplatin to gemcitabine/erlotinib confers a clinical benefit to patients with locally advanced or metastatic pancreatic cancer. Methods: Chemotherapy-naïve patients with locally advanced or metastatic pancreatic cancer were randomly assigned to receive GEMOX-T (gemcitabine 1000mg/m2 IV and oxaliplatin 50mg/m2 IV on day 1, 8 plus erlotinib 100mg daily, every 3weeks) or GT (gemcitabine 1000mg/m2 IV on day 1, 8 plus erlotinib 100mg daily, every 3weeks). The primary endpoint was overall response and secondary endpoints included PFS, overall survival (OS) and toxicity. Results: Between May 2013 and April 2016, 65 patients were randomly assigned to treatment group (33 in GEMOX-T arm, 32 in GT arm). The median age of all patients was 61 years (range, 41-76) and about 80% of patients had metastatic disease. The overall response rate was 18.2 % in GEMOX-T arm and 6.2% in GT arm ( P = 0.051). The disease control rate was significantly superior in GEMOX-T arm compared to GT arm (72.7% vs. 43.8%, P = 0.019), with 1 patient in GEMOX-T group continuing the treatment with stable disease. After a median follow up of 19.7 months, there was significant difference in PFS: the median PFS were 3.9 months for GEMOX-T arm and 1.4 months for GT arm (Hazard ratio: 0.58, 95% CI 0.35-0.96, P = 0.037). However, it did not translate to improvement of OS (median OS; 6.2 m for GEMOX-T arm, 5.1 m for GT arm, P = 0.118). The most common grade ≥ 3 hematologic adverse events were neutropenia (16.9%) and anemia (13.8%). Conclusions: The addition of oxaliplatin to 1st line gemcitabine/erlotinib regimen demonstrated higher response rate and significantly improved PFS in patients with locally advanced or metastatic pancreatic cancer.

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A randomized phase II study of gemcitabine (G) alone or with pazopanib (P) in refractory soft tissue sarcoma (STS).

Journal of Clinical Oncology ◽

10.1200/jco.2020.38.15_suppl.11515 ◽

2020 ◽

Vol 38 (15_suppl) ◽

pp. 11515-11515

Author(s):

Christopher W. Ryan ◽

Catherine Degnin ◽

Lee D. Cranmer ◽

Yiyi Chen ◽

Seth Pollack ◽

...

Keyword(s):

Statistical Power ◽

Response Rate ◽

Progression Free Survival ◽

Wilcoxon Test ◽

Double Blind Study ◽

Double Blind ◽

Randomized Phase Ii ◽

Common Grade ◽

Grade 3

11515 Background: Both G and P are active single-agents in the treatment of STS. We hypothesized that the anti-VEGF-R activity of P could augment the efficacy of G and conducted this study of G+P vs G+placebo (0). Methods: In this multi-center, double-blind study, eligibility included metastatic STS with receipt of 1–3 prior systemic regimens inclusive of an anthracycline. Patients (pts) were stratified by sarcoma subtype (liposarcoma (LPS) vs. other) and study site, then randomly assigned 1:1 to receive G 1000 mg/m2 IV over 30 minutes on days 1 and 8 every 21 days plus either P 800 mg PO or matching 0 daily. The primary endpoint was progression-free survival (PFS). Results: 54 pts were accrued from 2012–2019, Accrual was halted prior to the planned N of 80 due to withdrawal of funding. There were no differences in pt characteristics between the two arms including age (median = 60), sex (M/F 52/48%), histology (LPS 30%, leiomyosarcoma 26%, UPS 15%, synovial 11%, other 17%) and number of prior systemic therapies (median = 1). With a median follow-up of 19.1 months, PFS favored G+P and was significant using the Gehan-Wilcoxon test which favorably weighs earlier events (table). The response rate was 6.9% on the G+P arm and 8.0% on the G+0 arm; response rate was 22% for LPS treated with G+P. The most common grade ≥3 AEs (G+P v G+0) were: neutropenia (41% vs 40), hypertension (17% v 4), anemia (7% v 12). One patient died of hepatic failure on the G+P arm. Conclusions: This study demonstrated improved PFS with G+P as compared with G alone. Early termination limited statistical power. G+P is active in LPS, although P regulatory labeling currently limits use for LPS. Clinical trial information: NCT01532687 . [Table: see text]

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Phase II trial of gemcitabine + cisplatin + ipilimumab in patients with metastatic urothelial cancer.

Journal of Clinical Oncology ◽

10.1200/jco.2016.34.2_suppl.357 ◽

2016 ◽

Vol 34 (2_suppl) ◽

pp. 357-357 ◽

Cited By ~ 17

Author(s):

Matt D. Galsky ◽

Noah M. Hahn ◽

Costantine Albany ◽

Mark T. Fleming ◽

Alexander Starodub ◽

...

Keyword(s):

Adverse Events ◽

Response Rate ◽

Objective Response ◽

Progression Free Survival ◽

Immune Checkpoint Blockade ◽

Immunomodulatory Effects ◽

Free Survival ◽

Ctla4 Blockade ◽

Common Grade ◽

Grade 3

357 Background: Immune checkpoint blockade, with anti-PD-1/PD-L1 antibodies, has shown striking results in patients (pts) with mUC. While CTLA4 blockade has demonstrated pharmacodynamic effects in localized bladder cancer (Carthon, Clin Can Res, 2010), the role of CTLA4 blockade in mUC remains undefined. We hypothesized that chemotherapy may lead to immunogenic cell death, and other immunomodulatory effects, which could subsequently be exploited with the addition of ipilimumab. Methods: Pts with mUC received 2 cycles of gemcitabine + cisplatin (GC) alone followed by 4 cycles of GC + ipilimumab (GCIpi). The primary endpoint was % of patients alive at 1 year. Secondary endpoints included safety, objective response rate, and progression-free survival. Immune monitoring was performed at baseline, after GC alone, and after GCIpi. Results: 36 pts with mUC (median age 60; range: 33-80) were enrolled; KPS was 80%, 90% and 100% in 30%, 45%, and 25%; 58% had visceral metastases and 20% had liver metastases. Pts received a median of 5 cycles of GC (range: 1-6) and 3 doses of Ipi (range: 1-8). The most common grade 3-4 adverse events were neutropenia (36%), thrombocytopenia (19%), anemia (25%), hyponatremia (31%), thromboembolism (11%), and renal insufficiency (19%). The most common grade 3-4 immune-related adverse events were colitis (6%), hypophysitis (3%), hyperthyroidism (1%), and rash (1%). The objective response rate is shown in the Table. Median progression-free survival is 8 months (95% CI 6.2-9.8 months). Median follow-up is 10.4 months (range: 2.8-35.3 months). The primary endpoint analysis will be mature for the meeting. GC alone had no significant impact on circulating immune cell subsets; Ipi significantly expanded circulating CD4 and CD8 T cells. Conclusions: A phased schedule of GC plus immune checkpoint blockade was feasible in pts with mUC. Ipi induced immunomodulatory effects despite concurrent chemotherapy. Survival data are not yet mature. Ongoing analyses are exploring the impact of GC alone, and GCIpi, on antigen-specific T cell immunity and correlating such findings with “outlier” survival times. Clinical trial information: NCT01524991. [Table: see text]

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Response and Toxicity to the Second Course of 3 Cycles of 177Lu-PSMA Therapy Every 4 Weeks in Patients with Metastatic Castration-Resistant Prostate Cancer

Cancers ◽

10.3390/cancers13102489 ◽

2021 ◽

Vol 13 (10) ◽

pp. 2489

Author(s):

Sazan Rasul ◽

Tim Wollenweber ◽

Lucia Zisser ◽

Elisabeth Kretschmer-Chott ◽

Bernhard Grubmüller ◽

...

Keyword(s):

Response Rate ◽

Cox Regression ◽

Progression Free Survival ◽

Castration Resistant Prostate Cancer ◽

Radioligand Therapy ◽

Free Survival ◽

Castration Resistant ◽

Kaplan Meier ◽

Node Metastases ◽

Grade 3

Background: We investigated the response rate and degree of toxicity of a second course of three cycles of [177Lu]Lu-PSMA radioligand therapy (PSMA-RLT) every 4 weeks in mCRPC patients. Methods: Forty-three men (71.5 ± 6.6 years, median PSA 40.8 (0.87–1358 µg/L)) were studied. The response was based on the PSA level 4 weeks after the third cycle. The laboratory parameters before and one month after the last cycle were compared. Kaplan–Meier methods were used to estimate the progression-free survival (PFS) and overall survival (OS), and the Cox regression model was performed to find predictors of survival. Results: Twenty-six patients (60.5%) exhibited a PSA reduction (median PSA declined from 40.8 to 20.2, range 0.6–1926 µg/L, p = 0.002); 18 (42%) and 8 (19%) patients showed a PSA decline of ≥50% and ≥80%, respectively. The median OS and PFS were 136 and 31 weeks, respectively. The patients with only lymph node metastases survived longer (p = 0.02), whereas the patients with bone metastases had a shorter survival (p = 0.03). In the multivariate analysis, only the levels of PSA prior to the therapy remained significant for OS (p < 0.05, hazard ratio 2.43, 95% CI 1.01–5.87). The levels of hemoglobin (11.5 ± 1.7 g/dL vs. 11 ± 1.6 g/dL, p = 0.006) and platelets (208 ± 63 g/L vs. 185 ± 63 g/L, p = 0.002) significantly decreased one month after cycle three, though only two grade 3 anemia and one grade 3 thrombocytopenia were recorded. Conclusion: A further intensive PSMA-RLT course is well tolerated in mCRPC patients and associated with promising response rates and OS.

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Glembatumumab vedotin for patients with metastatic, gpNMB overexpressing, triple-negative breast cancer (“METRIC”): a randomized multicenter study

npj Breast Cancer ◽

10.1038/s41523-021-00244-6 ◽

2021 ◽

Vol 7 (1) ◽

Author(s):

Linda T. Vahdat ◽

Peter Schmid ◽

Andres Forero-Torres ◽

Kimberly Blackwell ◽

Melinda L. Telli ◽

...

Keyword(s):

Breast Cancer ◽

Triple Negative Breast Cancer ◽

Primary Endpoint ◽

Triple Negative ◽

Progression Free Survival ◽

Antibody Drug Conjugate ◽

Open Label ◽

Common Grade ◽

Open Label Phase ◽

Grade 3

AbstractThe METRIC study (NCT#0199733) explored a novel antibody–drug conjugate, glembatumumab vedotin (GV), targeting gpNMB that is overexpressed in ~40% of patients with triple-negative breast cancer (TNBC) and associated with poor prognosis. The study was a randomized, open-label, phase 2b study that evaluated progression-free survival (PFS) of GV compared with capecitabine in gpNMB-overexpressing TNBC. Patients who had previously received anthracycline and taxane-based therapy were randomized 2:1 to receive, GV (1.88 mg/kg IV q21 days) or capecitabine (2500 mg/m2 PO daily d1–14 q21 days). The primary endpoint was RECIST 1.1 PFS per independent, blinded central review. In all, 327 patients were randomized to GV (213 treated) or capecitabine (92 treated). Median PFS was 2.9 months for GV vs. 2.8 months for capecitabine. The most common grade ≥3 toxicities for GV were neutropenia, rash, and leukopenia, and for capecitabine were fatigue, diarrhea, and palmar-plantar erythrodysesthesia. The study did not meet the primary endpoint of improved PFS over capecitabine or demonstrate a relative risk/benefit improvement over capecitabine.

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Gemcitabine Plus Nab-Paclitaxel as Second-Line Chemotherapy following FOLFIRINOX in Patients with Unresectable Pancreatic Cancer: A Single-Institution, Retrospective Analysis

Chemotherapy ◽

10.1159/000517244 ◽

2021 ◽

pp. 1-7

Author(s):

Kotone Hayuka ◽

Hiroyuki Okuyama ◽

Akitsu Murakami ◽

Yoshihiro Okita ◽

Takamasa Nishiuchi ◽

...

Keyword(s):

Pancreatic Cancer ◽

Adverse Events ◽

Advanced Pancreatic Cancer ◽

Progression Free Survival ◽

Unresectable Pancreatic Cancer ◽

Line Treatment ◽

Second Line ◽

Free Survival ◽

Common Grade ◽

Grade 3

Introduction: Patients with advanced pancreatic cancer have a poor prognosis. FOLFIRINOX (FFX) and gemcitabine plus nab-paclitaxel (GnP) have been established as first-line treatment, but they have not been confirmed as second-line treatment after FFX. The aim of this study was to evaluate the safety and efficacy of GnP as second-line therapy after FFX in patients with unresectable pancreatic cancer. Methods: Twenty-five patients with unresectable pancreatic cancer were enrolled. The patients were treated with GnP after FFX between September 2015 and September 2019. Tumor response, progression-free survival (PFS), overall survival (OS), and incidence of adverse events were evaluated. Results: The response rate, disease control rate, median PFS, and median OS were 12%, 96%, 5.3 months, and 15.6 months, respectively. The common grade 3 or 4 adverse events were neutropenia (76%) and anemia (16%). Conclusions: GnP after FOLFIRINOX is expected to be one of the second-line recommendations for patients with unresectable pancreatic cancer.

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Lonsurf (trifluridine/tipiracil): Assessing the impact of dose related toxicities and progression free survival in (refractory) metastatic colorectal cancer

Journal of Oncology Pharmacy Practice ◽

10.1177/10781552211017973 ◽

2021 ◽

pp. 107815522110179

Author(s):

Olivia R Court

Keyword(s):

Colorectal Cancer ◽

Metastatic Colorectal Cancer ◽

Dose Reduction ◽

Progression Free Survival ◽

Electronic Patient Records ◽

Free Survival ◽

Length Of Treatment ◽

Common Grade ◽

Grade 3 ◽

The Impact

In the RECOURSE trial which lead to its accreditation, Lonsurf (trifluridine/tipiracil) was shown to extend progression free survival (PFS) by 1.8 months in metastatic colorectal cancer. This Trust audit aims to assess the average quantity of cycles of Lonsurf received by participants and the length of time it extends PFS. Similarly, to identify how many participants required a dose-reduction or experienced toxicities which necessitated supportive therapies. Quantitative data was collected retrospectively from all participants who had received ≥1 cycle of Lonsurf from The Clatterbridge Cancer Centre (CCC) from 2016 until June 2020. Participant electronic patient records were accessed to identify toxicity grading, length of treatment received, the date progression was identified, if dose reductions were applied and if supportive therapies were administered. Lonsurf extends PFS in patients with metastatic colorectal cancer at CCC by 3.0 months (95% CI: 2.73–3.27) and average treatment length was 2.4 months. However, 78 participants (41.5%) received a dose reduction due to toxicities. A total of 955 toxicities were recorded by participants; the most commonly reported toxicities irrespective of grade were fatigue (33.8%), diarrhoea (13.8%) and nausea (12.3%). The most common grade ≥3 toxicities were constipation and infection. The most frequently utilised supportive therapies were loperamide (49.6%) and domperidone (49.1%). Granulocyte colony stimulating factor (GCSF) was required by patients on 5 occasions (0.3%) in total. Lonsurf extends median PFS in patients with metastatic colorectal cancer by 3.0 months. The most common grade ≥3 toxicities which necessitated supportive therapies or a dose reduction were gastrointestinal and infection.

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Safety and efficacy of single-agent lenalidomide in patients with relapsed and refractory multiple myeloma

Blood ◽

10.1182/blood-2008-12-196238 ◽

2009 ◽

Vol 114 (4) ◽

pp. 772-778 ◽

Cited By ~ 110

Author(s):

Paul Richardson ◽

Sundar Jagannath ◽

Mohamad Hussein ◽

James Berenson ◽

Seema Singhal ◽

...

Keyword(s):

Multiple Myeloma ◽

Single Agent ◽

Progression Free Survival ◽

Prior Treatment ◽

Once Daily ◽

Free Survival ◽

Refractory Multiple Myeloma ◽

Treatment Regimens ◽

Common Grade ◽

Grade 3

Abstract Lenalidomide plus dexamethasone is effective for the treatment of relapsed and refractory multiple myeloma (MM); however, toxicities from dexamethasone can be dose limiting. We evaluated the efficacy and safety of lenalidomide monotherapy in patients with relapsed and refractory MM. Patients (N = 222) received lenalidomide 30 mg/day once daily (days 1-21 every 28 days) until disease progression or intolerance. Response, progression-free survival (PFS), overall survival (OS), time to progression (TTP), and safety were assessed. Overall, 67% of patients had received 3 or more prior treatment regimens. Partial response or better was reported in 26% of patients, with minimal response 18%. There was no difference between patients who had received 2 or fewer versus 3 or more prior treatment regimens (45% vs 44%, respectively). Median values for TTP, PFS, and OS were 5.2, 4.9, and 23.2 months, respectively. The most common grade 3 or 4 adverse events were neutropenia (60%), thrombocytopenia (39%), and anemia (20%), which proved manageable with dose reduction. Grade 3 or 4 febrile neutropenia occurred in 4% of patients. Lenalidomide monotherapy is active in relapsed and refractory MM with acceptable toxicities. These data support treatment with single-agent lenalidomide, as well as its use in steroid-sparing combination approaches. The study is registered at http://www.clinicaltrials.gov as NCT00065351.

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