Melphalan 200mg/m2 (MEL 200) and MEL 140/DT-PACE Are Equally Effective in Multiple Myeloma (MM), While the Latter Is Less Toxic.

Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 839-839 ◽  
Author(s):  
Guido Tricot ◽  
Maureen Reiner ◽  
Maurizio Zangari ◽  
Frits van Rhee ◽  
Bart Barlogie
Keyword(s):  
Febrile Neutropenia ◽  
Prior Therapy ◽  
Study Enrollment ◽  
Kaplan Meier ◽  
Rapid Responses ◽  
Preparative Regimen ◽  
Previously Treated ◽  
Baseline Characteristics ◽  
Grade 3 ◽  
Induction Cycle

Abstract MEL 200 is now generally accepted to represent the best preparative regimen for autotransplantation in MM patients. We have previously reported that DT-PACE is very effective in inducing rapid responses even in high risk myeloma (JCO 2003, 31: 73–80). The present study aimed at comparing outcome and toxicity of previously treated (≥ 2 cycles of prior therapy) MM patients, who were randomized to tandem transplants with either MEL 200 or MEL 140 plus full dose DT-PACE administered over two days (MEL/DT-PACE). The treatment in both arms consisted of one induction cycle with DT-PACE, followed by tandem transplants (randomized), one consolidation cycle with DT-PACE and 2 years of maintenance therapy with dexamethasone (20mg/d, days 1–4, every 3 weeks) plus thalidomide 100mg/day. 97 patients were enrolled; 93 collected sufficient stem cells for transplantation and were randomized to MEL 200 (N=48) or MEL140/DT-PACE (N=45). Event-free (EFS) and overall survival (OS) were analyzed using Kaplan-Meier plots. Graphs were compared with logrank statistics. Median age was 57 years. Prior to study enrollment β2M was ≥ 4mg/L in 28%; CRP ≥ 4 mg/L in 59%; LDH ≥ 250 U/L in 16%. 16% had > 12 months preceding therapy and 27% showed abnormal metaphase cytogenetics. Baseline characteristics were similar in both groups, except for a trend of more patients with β2M ≥ 4mg/: in the MEL 200 arm (p=0.09). 100% of randomized patients proceeded to the first transplant and 82% to a second; 87% in the MEL/DT-PACE and 77% in the MEL 200 arm (p=0.23). The CR rates were identical (44% and 42%, respectively). EF/OS at 3 years were 51%/71% in the MEL/DT-PACE arm and 55%/79% in the MEL 200 arm (p=.89/.73) (Figure 1). Recovery of ANC > 500μl plus platelets > 20,000/μl untransfused, was comparable after the first (p=0.21) and second transplant (p=0.17). Grade 3–5 toxicity was lower in the MEL/DT-PACE arm in terms of mucositis (p=.006) and febrile neutropenia (p=.001). We conclude that both preparative regimens, MEL 200 and 140 with the addition of DT-PACE, appear equally effective in previously treated MM patients. However, the Mel 140 resulted in a significantly lower incidence of mucositis and febrile neutropenia and may thus be preferred in patients not in excellent clinical condition prio to transplantation. Figure Figure

A Multi-Center, Open-Label Study To Evaluate the Safety and Efficacy of Pentostatin, Cytoxan, and Rituxan (PCR) in the Treatment of Previously Untreated or Treated, Stage III or IV, Low-Grade B-Cell Non-Hodgkin’s Lymphoma (NHL) or Bulky Stage II Lymphoma.

Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 1354-1354
Author(s):  
Raul R. Mena ◽  
Neil P. Christiansen ◽  
Yudhishtra Markan ◽  
Lalita Pandit
Keyword(s):  
Febrile Neutropenia ◽  
B Cell ◽  
Single Agent ◽  
Stage Ii ◽  
Stage Iii ◽  
Hematologic Toxicity ◽  
Low Grade ◽  
Purine Analog ◽  
Previously Treated ◽  
Grade 3

Abstract The decision to treat indolent B-cell NHL is often based on progression of the disease. Most regimens have utilized fludarabine as the purine analog but the myelosuppression and immunosuppression of fludarabine combinations frequently results in severe infections. Combination therapy with pentostatin (P), a purine analog, cyclophosphamide (C), a DNA alkylator, and rituximab (R), an anti-CD20 monoclonal antibody, based on the single-agent activities, documented synergy, and non-overlapping toxicity profiles, may represent a promising approach in the treatment of these patients. To further investigate the efficacy of the PCR regimen for the treatment of indolent NHL, we conducted a phase II study. Patients diagnosed of bulky stage II, stage III/IV low-grade NHL (REAL classification), previously untreated or treated, were eligible. All patients were treated with intravenous infusions of P (4 mg/m2), C (600 mg/m2), and R (375 mg/m2) on day 1 of a 21-day cycle for at least 8 cycles. 2 additional cycles were given for patients with PR or SD after cycle 8 or patients with CR/CRu first evident at cycle 8. Clinical evaluation was performed after cycles 2, 4, 6, 8, and 10 if necessary. Dose modification for hematologic toxicity may be increased to the previous higher level when a hematologic toxicity returned to normal. Two 25% dose reductions or one 50% dose reduction were allowed for nonhematologic toxicity. One hundred patients with indolent NHL, 68 previously untreated, 26 previously treated, and 6 with unknown treatment history, were enrolled in the study. The median age was 61 years (range 29–84) and 63.4% were ECOG PS 0, 36.6% PS1. A total of 550 cycles were given, with a median of 6 cycles per patient. 8 patients were not evaluated for response due to withdrawal of consent (n=1), unacceptable toxicities (n=3), and missing data (n=4). 92 patients received at least two cycles of treatment and were evaluated for response. The highest response rate (RR) achieved was 68%, with 10 (10%) CR, 12 (12%) CRu, 46 (46%) PR, 23 (23%) SD, and 1 (1%) disease progression. Stratified according to previous treatment status, patients with previously untreated NHL had an RR of 47% (CR, CRu 17%) while that of the previously treated was 17% (CR 7%). 14 (14.0%) patients discontinued treatment due to toxicities. Grade 3/ 4 hematological adverse events documented included 10 grade 4 and 16 grade 3 neutropenia. Infectious complications were noted in 8 patients including 3 grade 3 febrile neutropenia, 2 grade 4 febrile neutropenia, and 3 grade 3 infections. A total of 4 deaths were recorded, including 1 due to acute myocardial infarction, 1 suspected cardiac event and 2 unknown causes. This immunochemotherapeutic regimen is active in patients with indolent NHL. The study is currently on-going and updated results will be presented.

Efficacy and safety of bevacizumab in nonsquamous non-small cell lung cancer with brain metastases.

2013 ◽  
Vol 31 (15_suppl) ◽  
pp. e19134-e19134
Author(s):  
Masao Ichiki ◽  
Tsukasa Yoshida ◽  
Masayuki Nakamura ◽  
Tomomi Kumano ◽  
Tomoaki Hoshino
Keyword(s):  
Brain Metastases ◽  
Response Rate ◽  
Concurrent Chemotherapy ◽  
Bleeding Events ◽  
Mutation Status ◽  
Prior Therapy ◽  
Mri Scans ◽  
Previously Treated ◽  
Grade 3 ◽  
Extracranial Metastases

e19134 Background: Patients (pts) with brain metastases were excluded from bevacizumab (Bev) therapy due to a case of fatal cerebral hemorrhage in 1997. However, several trials showed the safety of Bev in pts with inactive (previously treated or asymptomatic) brain metastases, and Bev therapy was recently permitted as practical care for brain metastases in Japan. Methods: We retrospectively identified pts treated with Bev for inactive brain metastases from NSCLC. CT or MRI scans performed at least 6 weeks after Bev therapy were assessed for response. Results: There were 17 pts. All pts had adenocarcinoma. Median age was 66 (range 57-74), male/female= 8/9, PS0/1/2= 3/10/4, 1st-/2nd-/3rd-/4th-line chemotherapy with Bev = 8/4/4/1, EGFR mutation status; mutated/wild type/unknown=8/7/2; concurrent chemotherapy with Bev: amrubicin (1), pemtrexed (2), cisplatin (carboplatin) + pemetrexed (10), carboplatin + paclitaxel (3), cisplatin + gemcitabine (1); prior chemotherapy: gefitinib (6), erlotinib (3), docetaxel (1), carboplatin + paclitaxel (2), cisplatin + pemetrexed (2), pemetrexed (1); prior therapy for brain metastases: surgery (1), surgery + WBRT (2),WBRT (8), SRS (4), none (2). In 14 pts with evaluable target brain metastases, the response rate for intracranial metastases was 78.6% (95% CI, 49.2-95.4%), and in 15 pts with evaluable target lesions except brain metastases, the response rate for extracranial metastases was 40.0% (95% CI, 16.3-67.7%). Serious toxicities (grade 3/4): hypertension (2/0), proteinuria (0/-). There were 2 bleeding events: one was grade 1 intracraninal hemorrhage, the other was grade 1 bronchopulumonary hemorrhage. Conclusions: Chemotherapy+Bev is effective for pts with inactive brain metastases and is a well-tolerated regimen with a favorable toxicity profile. The updated data including PFS and OS will be presented at the Annual Meeting.

Expanded analyses of napoli-1: Phase 3 study of MM-398 (nal-IRI), with or without 5-fluorouracil and leucovorin, versus 5-fluorouracil and leucovorin, in metastatic pancreatic cancer (mPAC) previously treated with gemcitabine-based therapy.

2015 ◽  
Vol 33 (3_suppl) ◽  
pp. 234-234 ◽  
Author(s):  
Li-Tzong Chen ◽  
Daniel D. Von Hoff ◽  
Chung-Pin Li ◽  
Andrea Wang-Gillam ◽  
Gyorgy Bodoky ◽  
...  
Keyword(s):  
Sensitivity Analyses ◽  
Open Label ◽  
Phase 3 ◽  
Open Label Study ◽  
Prior Therapy ◽  
Previously Treated ◽  
Grade 3 ◽  
Intent To Treat ◽  
To Receive ◽  
Clinical Trial Information

234 Background: MM-398 is a nanoliposomal encapsulation of irinotecan. OS in the ITT population was significantly longer with MM-398+5FU/LV over 5FU/LV alone, and the most frequent grade 3+ AEs included neutropenia, fatigue, and GI effects (diarrhea and vomiting). Expanded, pre-specified analyses of the Phase 3 study are presented. Methods: Patients (n=417) with mPAC previously treated with gemcitabine-based therapy, were randomized 1:1:1 in an open-label study to receive: (A) MM-398 (120 mg/m2 IV over 90 min) q3w; (B) 5FU (2,000 mg/m2 over 24 h) plus racemic leucovorin (LV) (200 mg/m2 over 30 min) x 4w followed by 2w rest; or (C) combination of MM-398 (80 mg/m2 IV over 90 min) prior to 5FU (2,400 mg/m2 over 46 h) and racemic LV (400 mg/m2 over 30 min) q2w. The primary endpoint was OS. The Intent To Treat (ITT) population included all randomized patients; the Per Protocol (PP) population included patients who received at least 80% of the target dose in the first 6 weeks and did not violate any inclusion/exclusion criteria. Results: Analysis of the PP populations confirmed the favorable OS, which was also reflected by the PFS, ORR and CA19-9 levels, of the combination MM-398+5FU/LV arm over the control 5FU/LV arm. The MM-398 monotherapy arm did not show a statistically significant improvement in OS compared with the control arm. Analysis of subgroups, based on pretreatment characteristics including stage at diagnosis, time since initial histological diagnosis, prior lines of therapy, time since last prior therapy, and CA19-9 levels, consistently favored OS for the MM-398+5FU/LV arm over the 5FU/LV arm. Conclusions: Expanded analysis of the PP population and sensitivity analyses support the favorability of MM-398+5FU/LV over 5FU/LV, with a manageable safety profile. Clinical trial information: NCT01494506. [Table: see text]

Panitumumab (Pmab) versus cetuximab (Cmab)/irinotecan (Iri) therapy among patients with KRAS wild-type (wt) metastatic colorectal cancer (MCRC).

2012 ◽  
Vol 30 (4_suppl) ◽  
pp. 640-640 ◽  
Author(s):  
Hagen F. Kennecke ◽  
Leo Chen ◽  
C. D. Blanke ◽  
Winson Y. Cheung ◽  
Kimberly Schaff ◽  
...  
Keyword(s):  
Overall Survival ◽  
Performance Status ◽  
Similar Proportion ◽  
Wild Type ◽  
Prognostic Variables ◽  
Ecog Performance Status ◽  
Cancer Centers ◽  
Kaplan Meier ◽  
Previously Treated ◽  
Baseline Characteristics

640 Background: In British Columbia, use of anti-EGFR therapy for KRAS wt MCRC is limited to patients (pts) previously treated with both irinotecan and oxaliplatin. Physicians may choose either Pmab monotherapy or Cmab/Iri combination therapy. We sought to compare the characteristics and outcomes of all pts treated with Pmab/Cmab referred to 5 provincial cancer centers since July, 2009. Methods: Eligible patients received at least one dose of either Pmab (6mg/kg q2w) or Cetuximab (500mg/m2 q2w) plus Iri (180mg/m2 q2w). Baseline characteristics and systemic therapy were prospectively collected, while ECOG and metastatectomy status were retrospectively collected. Kaplan-Meier survival analysis was conducted from the first day of Pmab/Cmab. Results: Among 178 eligible pts, Pmab was chosen 3 times more often than Cmab/Iri (see table). Pts treated with Cmab/Iri were significantly younger and had better performance status than those treated with Pmab. There were no statistically significant differences in other prognostic variables, and a similar proportion received chemotherapy after Pmab vs. Cmab/Iri. Overall survival was slightly longer among patients receiving Cmab/Iri (8.3 mo), vs. Pmab (7.7 mo) (p=.03). Conclusions: Pmab was chosen more often than Cmab/Iri for similarly eligible patients. Cmab/Iri pts were younger, were more likely to have ECOG performance status 0/1 and achieved a modestly longer overall survival. Either regimen appears to be suitable for previously treated pts with KRAS wt MCRC. [Table: see text]

Ipilimumab in the real world: The U.K. expanded access programme (EAP) experience in advanced melanoma.

2013 ◽  
Vol 31 (15_suppl) ◽  
pp. 3018-3018 ◽  
Author(s):  
Saif Ahmad ◽  
Wendi Qian ◽  
Sarah Gabrielle Ellis ◽  
Muhammad Adnan Khattak ◽  
Avinash Gupta ◽  
...  
Keyword(s):  
Real World ◽  
Progression Free Survival ◽  
Advanced Melanoma ◽  
Survival Outcomes ◽  
Prior Therapy ◽  
Access Programme ◽  
Previously Treated ◽  
Registration Trial ◽  
Grade 3 ◽  
Ecog Ps

3018 Background: Since publication of the registration trial in 2010 (Hodi et al, NEJM 2010;363:711-23), real world use of ipilimumab (Ipi) in previously treated advanced melanoma patients has extended beyond the specific trial entry criteria of ECOG PS 0-1. We undertook a review of UK patients (pts) treated in the international EAP prior to European licensing of Ipi in August 2011, to compare real world survival outcomes. Methods: UK clinicians registered in the EAP provided anonymised data using pre-specified variable fields for all pts. The EAP stipulated pts should have previously treated, unresectable stage III or IV metastatic melanoma and receive Ipi 3 mg/kg, 3 weekly IV, for up to 4 cycles. Response using RECIST criteria was assessed 12 weekly. Grade ≥3 adverse events (AEs) using CTCAE v3.0 were collected. Results: To date, information on 162 pts has been received from 16 UK sites. Primary sites were: 78% cutaneous, 4% ocular, 1% mucosal, 17% unknown. 78% pts had M1c disease, 14% had brain metastases. No prior therapies ranged from 0-4, 72% pts received 1 prior therapy. Median age was 60 years, men>women (1.6:1). ECOG PS was: 38% 0, 47% 1, 14% 2, 1% 3. BRAF status was known in 38% cases and WT in 75% of these. 19% pts were on steroids at baseline. No cycles delivered was 4 in 52%, 3 in 13%, 2 in 16%, 1 in 17% pts. Most frequent reason for stopping early was clinical evidence of disease progression (71%), death (16%) or unacceptable AE (12%). 32% pts experienced a grade ≥3 AE, the most common being diarrhoea (13%) and fatigue (8%). Complete and partial responses were reported in 1% and 21% of treated pts. At median follow-up of 17 months, median progression free survival and overall survival (OS) were 2.8 and 5.7 months, 1 year OS was 30%. Comparing outcomes of various pt subgroups, the strongest prognostic factor for OS was ECOG PS at the start of treatment (p<0.0001). For pts with PS 0 or 1, median OS was 8.8 months (compared with 10 months in the registration trial). More detailed safety and efficacy data on pt subgroups will be presented. Conclusions: This review, representing the largest Ipi EAP UK dataset, reports overall poorer survival outcomes than in the registration trial, but pts with similar characteristics to the trial population lived longer.

Outcomes with rituximab plus bendamustine (R-Benda), dexamethasone, rituximab, cyclophosphamide (DRC), and bortezomib, dexamethasone, rituximab (BDR) as primary therapy in patients with Waldenstrom macroglobulinemia (WM).

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. 7509-7509 ◽  
Author(s):  
Jithma P. Abeykoon ◽  
Saurabh Zanwar ◽  
Stephen M. Ansell ◽  
Shaji Kumar ◽  
Carrie A. Thompson ◽  
...  
Keyword(s):  
Primary Therapy ◽  
Time To Event ◽  
Waldenström Macroglobulinemia ◽  
Entire Cohort ◽  
Waldenstrom Macroglobulinemia ◽  
Kaplan Meier ◽  
Baseline Characteristics ◽  
Frontline Therapy ◽  
Grade 3

7509 Background: Waldenstrom macroglobulinemia (WM) is a rare lymphoma for which scant comparative data exist to guide frontline therapy. Herein, we compare 3 commonly used regimens in WM: R-Benda, DRC, and BDR in frontline setting. Methods: Patients (Pts) with active WM seen at Mayo Clinic between 2000 & 2018 who received R-Benda, DRC or BDR as primary therapy were included in this retrospective study. Response rates were assessed by Consensus Criteria. All time to event analyses were performed from the frontline therapy, using Kaplan-Meier method. Results: The study included 172 pts with active WM (R-Benda, n=67, DRC, n=75, BDR, n=30).The median follow-up for the entire cohort was 3.7 years (y) (95% CI 3.7-3.0). Baseline characteristics, including IPSS, and time to frontline therapy from WM diagnosis were similar across the 3 cohorts. Clinically relevant endpoints are shown in the Table. Hematologic and non-hematologic toxicities were similar across the 3 groups. Grade 3 neuropathy requiring treatment discontinuation was encountered in 13% pts treated with BDR. 56 pts received subsequent salvage therapy [(10% in R-Benda arm, 44% in DRC arm, & 53% in BDR arm]; 29% pts in the R-Benda arm and 30% pts in DRC arm received a PI-based regimen while 69% pts in the BDR arm received alkylator-rituximab based therapy. Conclusions: Outcomes (MRR, TTNT and EFS) with frontline R-Benda are superior in comparison to frontline DRC or BDR in patients with WM. Clinically relevant endpoints are not significantly different with DRC vs. BDR. The toxicity profile across the 3 groups was comparable. [Table: see text]

Once weekly selinexor, carfilzomib, and dexamethasone (SKd) in patients with relapsed/refractory multiple myeloma (MM).

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. 8530-8530 ◽  
Author(s):  
Cristina Gasparetto ◽  
Brea Lipe ◽  
Sascha Tuchman ◽  
Natalie Scott Callander ◽  
Suzanne Lentzsch ◽  
...  
Keyword(s):  
Weight Loss ◽  
Nuclear Export ◽  
Progression Free Survival ◽  
Median Number ◽  
Maximum Tolerated Dose ◽  
Nuclear Retention ◽  
Prior Therapy ◽  
Previously Treated ◽  
Phase 1B ◽  
Grade 3

8530 Background: Selinexor is a novel, first-in-class selective inhibitor of nuclear export (SINE), which blocks exportin 1 (XPO1), forcing the nuclear retention and activation of tumor suppressor proteins. Selinexor in combination with low dose dexamethasone (Sel-dex) was approved by the FDA, based on data from the STORM study wherein Sel-dex induced an overall response rate (ORR) of 26.2% in patients (pts) with refractory MM. We hypothesize that once weekly (QW) SKd may be an active well tolerated regimen and evaluated this combination in a dose escalation/expansion study. Methods: STOMP is a phase 1b/2 study evaluating various doses and enrolled pts with carfilzomib naive relapsed MM. Oral selinexor was dosed QW at 80 or 100 mg. Carfilzomib was dosed QW (on days 1, 8 and 15 of 28-day cycle) at 56 mg/m2 or 70 mg/m2. Dexamethasone was dosed at 40 mg QW. The primary objectives of the study are to assess the maximum tolerated dose (MTD), recommended phase 2 dose (RP2D), as well as explore the efficacy and safety of SKd. Results: As of January 2020, 18 pts were enrolled. Median age was 71 years (range: 50-76). Median number of prior regimens was 4 (range: 1-8). All pts (n = 18) were previously treated with bortezomib and lenalidomide, and 50% and 56% pts were refractory to bortezomib and lenalidomide respectively. Nine (50%) pts received prior pomalidomide treatment and 8 (44%) pts were refractory. Eleven (61%) pts received prior daratumumab treatment and 9 (50%) were refractory. The MTD was selinexor 80 mg QW, carfilzomib 56 mg/m2 QW and dexamethasone 40 mg QW. The ORR and CBR were 72% and 79% respectively with 4 complete responses, 7 very good partial responses, 2 partial responses, and 1 minimal response. Stable disease was observed in 3 pts. With a median follow-up period of 4.7 (1.8-16.3) months, median progression-free survival has not been reached. Common treatment-related adverse events (total, Grade ≥3) were thrombocytopenia (83.3%, 66.7%), nausea (66.7%, 0%), anemia (55.6%, 11.1%), fatigue (50%, 11.1%), anorexia (44%, 5.6%), weight loss (44%, 0%), and neutropenia (33.3%, 11.1%). Conclusions: Once weekly SKd demonstrated an encouraging ORR of 72% in pts with a median of 4 lines of prior therapy. The majority of responses are deep and predominantly CR and VGPR. The combination is well tolerated with no new safety signal, no Grade ≥3 nausea, vomiting, diarrhea, weight loss or anorexia. The side effects are a function of the dose and schedule and can be managed with dose modification and supportive care. Enrolment is ongoing and supports a phase 3 study of SKd. Clinical trial information: NCT02343042 .

Treatment of locally advanced or multiple basal cell carcinoma with vismodegib in real world setting.

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. e22065-e22065
Author(s):  
Janja Ocvirk ◽  
Tanja Mesti ◽  
Katja Leskovsek
Keyword(s):  
Basal Cell Carcinoma ◽  
Adverse Events ◽  
Cell Carcinoma ◽  
Real World ◽  
Locally Advanced ◽  
Muscle Cramps ◽  
Real World Setting ◽  
Previously Treated ◽  
Baseline Characteristics ◽  
Grade 3

e22065 Background: Evaluation of efficacy and safety of vismodegib (V) was done in a retrospective analysis of patients (pts) with locally advanced or multiple basal cell carcinoma (laBCC or multiple BCC) and pts with Goltz-Gorlin Syndrom (G-G Syn) in routine clinical practice. Methods: Baseline characteristics, efficacy data and treatment-related adverse events were collected from 30 laBCC or multiple BCC and 6 G-G Syn pts who were treated with V. Results: In 86-month period, 36 pts were diagnosed with laBCC (18 pts), multiple BCC (12 pts) or G-G Syn (6 pts), all inappropriate for surgery or radiotherapy. Baseline characteristics: median age was 72.6 years in laBCC + multiple BCC pts group and 51.3 years in G-G Syn pts group. Sixty percent of pts in laBCC + multiple BCC group were females; majority (70%) of pts were previously treated by surgery (S) and/or radiotherapy (RT); 43% of pts had 1 lesion with predominant localization in central face (eyes, nose, lips or ears in 84% of pts), 20% had 2-3 lesions and 37% more than 3 lesions. Fifty percent of pts in G-G Syn pts group were males; all pts were previously treated with S and/or RT. The overall response rate (ORR) was 76% in laBCC + multiple BCC and 83% in G-G Syn pts group. Disease control rate (DCR) was 93% in laBCC + multiple BCC and 100% in G-G Syn pts group. Median duration of treatment (DoT) was 7.8 months (range: 1.3-29.8) in laBCC + multiple BCC group and 27.1 months (range: 4.8-86.4) in G-G Syn group. At the time of analysis in laBCC or multiple BCC group one patient died due to other reasons than cancer, in 30% of pts treatment has been interrupted during the treatment course [in most cases due to complete response or adverse events (AEs)], 40% of pts are still on treatment. In G-G Syn group treatment has been interrupted in 50% of pts (in most cases due to adverse events), 67% of pts are still on treatment. AEs of any grade were reported in 97% of pts in laBCC or multiple BCC group and 83% in G-G Syn group. Majority of AEs in laBCC or multiple BCC group were grade 1 or 2 (96%)., 4% of AEs were grade 3: muscle cramps in 3 pts, respiratory infection, vomiting and anemia in 1 patient each. Majority of AEs in G-G Syn group were also grade 1 or 2 (87%), 13% of AEs were grade 3: muscle cramps in 2 pts, weight loss and diarrhea in 1 patient each. No grade 4 or 5 AEs were reported. Conclusions: Vismodegib has shown meaningful efficacy with manageable safety profile in pts with laBCC or multiple BCC as well as in pts with G-G Syn in real world setting.

The Influence of Age on Outcomes in Patients Who Receive Autologous Stem Cell Transplantation.

Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 5463-5463
Author(s):  
Dawn M. Goodyear ◽  
Yvonne Gulliver ◽  
Peter R. Duggan
Keyword(s):  
Stem Cell ◽  
Febrile Neutropenia ◽  
Older Patients ◽  
Older Patient ◽  
Cell Dose ◽  
Hematopoietic Recovery ◽  
Transfusion Requirements ◽  
Baseline Characteristics ◽  
Grade 3 ◽  
Related Mortality

Abstract Introduction: Most randomized trials that evaluate the use of autologous stem cell transplantation (ASCT) exclude older patients due to the expectation of more complications and higher mortality. There is little prospective randomized data assessing the benefit of ASCT in older patient groups. Despite this, ASCT is frequently being offered to older patients with myeloma and NHL. The aim of this project is to compare outcomes of patients younger and older than 60 years of age who have received an ASCT. Methods: Review of a prospective database of all patients who have undergone ASCT at the St. John’s Health Sciences Centre since 2001. Outcome data collected included hematopoietic recovery and transfusion requirements, occurrence of NCI grade 3 or 4 toxicity (hematologic toxicity excluded), and transplant-related mortality. Mild (grade1–2) toxicity was not compared. The rate of febrile neutropenia was studied separately from other NCI toxicities. Results: Between November 2001 and June 2006 stem cell mobilisation was attempted in 125 patients and was successful in 113 (90%). Mobilisation failed in 5/45 (11%) of older patients and 7/80 patients under 60 (9%) (p=0.70). Transplant has not been performed in 17 patients (8 patients have cells stored for future use, 9 patients progressed or developed severe new health issues). 96 patients underwent ASCT. Four patients had a second ASCT during this period, but only data from the first transplant was included in this study. There were 33 patients age ≥ 60 and 63 patients < 60 years. Baseline characteristics are presented in Table 1. Though there was no difference in the median stem cell dose received, when patients were grouped according to the dose received (<2.5, 2.5–5.0, 5.0–10, and > 10 × 106/kg) we see that older patient were more likely to receive a lower stem cell dose (p = 0.033). Despite this, hematopoietic recovery was similar between the two groups. There was no significant difference between time to neutrophil recovery, platelet recovery, transfusion requirements, GCSF administration, and duration of hospitalization (table 2). Febrile neutropenia occurred in 75% of patients < 60 versus 81% of those ≥ 60 (p=ns). Grade 3 or 4 toxicity was experienced by 68% and 67% respectively. There was one death due to transplant related complications in the younger age group, and none in the older group. Conclusion: This study showed no difference in recovery, toxicity, or transplant-related mortality between younger and older patients after ASCT. Table 1: Baseline Characteristics < 60 years ≥ 60 years Number of patients 63 33 Male 41 18 Female 22 15 Median Age (Range) 49.6 (21–59) 64.6 (60–73) Diagnosis Non-Hodgkins Lymphoma 28 15 Multiple Myelom 24 17 Hodgkins Disease 9 1 Other 2 0 Conditioning Regimen BEAM 30 13 Melphalan 27 18 Other 6 2 Stem Cell Dose Median CD34 dose* (average, range) 5.7 (7.8, 2.7–50.9) 5.3 (5.7, 2.1–18.4) # receiving < 2.5* 0 4 2.5 – 5.0* 20 12 5.0 – 10.0* 36 14 > 10.0* 7 3 Table 2: Hematologic Recovery < 60 ≥ 60 P-Value Median days to ANC > 0.5 ×109 (range) 10 (8–12) 10 (9–12) .21 Median days to Platelets > 20 (range) 11 (7–54) 11 (8–67) .13 Median RBC Transfusions (ave, range) 0 (1.5, 0–12) 1 (1.9, 0–7) .49 Median platelet transfusions (ave, range) 1 (1.9, 0–26) 2 (1.7, 0–7) .77 Median Days of G-CSF 6 7 .25 Ave # Days in hospital from day 0 – 60 13.2 (0–60) 13.8 (0–35) .79

Ramucirumab (RAM) for sorafenib intolerant patients with hepatocellular carcinoma (HCC) and elevated baseline alpha fetoprotein (AFP): Outcomes from two randomized phase 3 studies (REACH, REACH2).

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. 4073-4073 ◽  
Author(s):  
Josep M Llovet ◽  
Chia-Jui Yen ◽  
Richard S. Finn ◽  
Yoon-Koo Kang ◽  
Masatoshi Kudo ◽  
...  
Keyword(s):  
Objective Response ◽  
Proportional Hazard ◽  
Cox Proportional Hazard ◽  
Kaplan Meier ◽  
Baseline Characteristics ◽  
Grade 3 ◽  
Ecog Ps ◽  
Require Dose ◽  
Require Dose Adjustment ◽  
Clinical Trial Information

4073 Background: Oral multikinase inhibitors that have shown improvements in overall survival (OS) in HCC are associated with clinically important toxicities that commonly require dose adjustment or discontinuation (D/C) due to intolerance. REACH and REACH-2 studied RAM in patients (pts) with HCC who progressed on or were intolerant to sorafenib (SOR), and REACH-2 only enrolled pts with baseline AFP ≥400 ng/mL. In REACH-2 RAM treatment (trt) improved OS compared to placebo (P), supporting findings in REACH pts with baseline AFP ≥400 ng/mL. An exploratory analysis of outcomes by reason for D/C of SOR was performed. Methods: Pts had advanced HCC, Child-Pugh A, ECOG PS 0-1, and prior SOR. Pts were randomized to RAM 8 mg/kg or P Q2W. A pooled independent pt data analysis (stratified by study) of REACH-2 and REACH pts (AFP ≥400 mg/mL) was performed. Results are reported by reason for SOR D/C (intolerance or disease progression). OS and PFS were evaluated using Kaplan-Meier method and Cox proportional hazard model. Objective response rate (ORR), disease control rate (DCR) and safety are reported. Results: Baseline characteristics in the pooled population were generally balanced between trt arms in each subgroup. Median durations of prior SOR were 2.5 mo for SOR intolerant (n = 70) and 4.0 mo for SOR progressors (n = 472). Median OS (RAM v P) was 10.2 v 6.7 mo for SOR intolerant and 8.0 v 4.7 mo for SOR progressors (Table). Rates of D/C due to trt-related adverse events (AEs) (Table) (7% in each subgroup), and Grade ≥3 AEs (most frequently hypertension) were consistent with those observed in each study. Conclusions: Acknowledging limitations of sample size, the RAM trt benefit in SOR intolerant pts was consistent with that in the ITT population. RAM was well tolerated in SOR intolerant pts with low rates of D/C due to related-AEs. Clinical trial information: NCT01140347, NCT02435433. [Table: see text]

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