Gemcitabine/cisplatin in patients with advanced bladder and impaired renal function: A retrospective analysis.

2011 ◽  
Vol 29 (7_suppl) ◽  
pp. 274-274
Author(s):  
R. Morales ◽  
C. Serrano ◽  
J. Bellmunt ◽  
B. Mellado ◽  
M. Guix ◽  
...  
Keyword(s):  
Bladder Cancer ◽  
Renal Function ◽  
Impaired Renal Function ◽  
Locally Advanced ◽  
Progression Free Survival ◽  
Complete Response ◽  
Median Number ◽  
Weekly Schedule ◽  
Unfit Patients ◽  
Grade 3

274 Background: A four-weekly regimen of gemcitabine and cisplatin (GEMCIS) has similar activity and is less toxic than MVAC in advanced bladder cancer. However, full-dose cisplatin in unfit patients with impaired renal function is contraindicated and other carboplatin-based schedules have been developed. We have previously reported the feasibility of GEMCIS in a biweekly schedule in unfit patients with renal impairment. Here we report a multicenter retrospective study of this biweekly regimen in patients with impaired renal function. Methods: Between January 2004 and October 2009, 40 patients with locally advanced nonsurgically resectable or metastatic bladder cancer and impaired renal function were included. Treatment consisted of gemcitabine 2500 mg/m2 on day 1 and cisplatin 35 mg/m2 on day 1, every 14 days. Results: Median age of the patients was 73 years (range: 51-82 years). Median IK was 80% (range: 60-100%). Mean creatinine clearance was 49 ml/min (range:37-59 ml/min). Eight patients had previously received chemotherapy with gemcitabine and/or platinum based therapy. Metastatic localizations were: 17 lymph nodes, 10 pulmonary, 10 bone, 7 liver, 12 pelvic and 1 central nervous system. The median number of cycles/patient was 6 (1-13). Out of 36 patients evaluable for response, there was one complete response, 14 partial responses (ORR: 42%; 95% CI 27-58%), 11 stabilizations and 10 progressive diseases. Hematologic toxicities were grade 1 anaemia in 15 patients, grade 2 in 8; grade 3 in 2; grade 3 neutropenia in 5 patients and grade 4 in 1 patient; grade 3 plaquetopenia in 3 patients. Nonhematologic toxicities were grade 1-2 vomiting in 2 patients. Two patients showed a grade 2 hepatic toxicity. Worsening of the renal function was observed in two patients. Alopecia grade 1-2 was seen in three patients. There was one toxic death related to metabolic acidosis.The median progression-free survival is 15 weeks. The median OS from first cycle of GEMCIS is 35 weeks and 1-year OS is 43% (St error 9%). Conclusions: A two-weekly schedule of gemcitabine plus cisplatin is feasible, active, and generally well tolerated in an outpatient setting in unfit patients with poor renal reserve. No significant financial relationships to disclose.

Investigate the efficacy of immunotherapy for treatment of pancreatic adenocarcinoma (PDAC) with mismatch repair deficiency (dMMR).

2021 ◽  
Vol 39 (3_suppl) ◽  
pp. 415-415
Author(s):  
Arish Noor ◽  
Luis E. Aguirre ◽  
Kirsten Blue ◽  
Trenton Avriett ◽  
Estrella M. Carballido ◽  
...  
Keyword(s):  
Pancreatic Adenocarcinoma ◽  
Metastatic Disease ◽  
Checkpoint Inhibitors ◽  
Objective Response ◽  
Locally Advanced ◽  
Progression Free Survival ◽  
Complete Response ◽  
Median Number ◽  
Cancer Center ◽  
Duration Of Response

415 Background: Immune checkpoint inhibitors (ICI) have been approved in solid tumors with dMMR. However, only limited data are available for PDAC with dMMR given the rarity of dMMR in PDAC. We evaluated efficacy of ICIs in PDAC with dMMR. Methods: Retrospective clinical and pathologic data were collected for patients (pts) with pancreatic adenocarcinoma from May 2017 to June 2020 at Moffitt cancer center. Results: We identified 10 pts with dMMR PDAC. The median age was 64.5 years (range: 42-86) and 4 pts were male. 4 pts had resectable disease, 3 had locally advanced and 3 had metastatic disease at initial diagnosis. MSH6 deficiency (def) was found in 2 cases, PMS2 def in 2, MLH/PMS2 def in 5, and MSH2/MSH6 in 1. 7 pts were treated with ICIs. 3 pts had locally advanced and 4 had metastatic disease when they started ICIs. 5 received Pembrolizumab (pem), 1 received ipilimumab/ nivolumab (ipi/nivo), and 1 received pem then ipi/nivo after progressive disease (PD) on pem. The median number of prior lines of chemotherapy was 1 (range 0-2). 6 pts were evaluable, and 1 had rapid disease progression after 1 dose of pem. Among 6 evaluable pts, 3 had an objective response (1: complete response and 2: partial response), and 2 had stable disease (SD). Median progression-free survival was 8.2 mo, and median overall survival was not reached with median follow-up (FU) of 6.8 mo. The median duration of response was not reached with a median FU of 22.6 mo. The pt with CR remained disease-free for up to 22 months. The pt whose treatment was switched to ipi/nivo after PD on pem achieved SD > 4mo on ipi/nivo. While on immunotherapy, one patient with ipi/nivo developed immunotherapy associated rash requiring systemic steroids, and another on pem developed hypothyroidism requiring levothyroxine. Conclusions: This series suggest ICIs can provide durable clinical efficacy in pts with dMMR PDAC.

Concomitant radical non-platinum radiochemotherapy for elderly patients with invasive bladder cancer

2009 ◽  
Vol 27 (15_suppl) ◽  
pp. e16135-e16135
Author(s):  
A. Rodica Maricela ◽  
L. N. Minea ◽  
X. Bacinschi ◽  
I. Isacu ◽  
A. Tarlea
Keyword(s):  
Bladder Cancer ◽  
Elderly Patients ◽  
Performance Status ◽  
Locally Advanced ◽  
Conformal Radiotherapy ◽  
Distant Metastases ◽  
Complete Response ◽  
Bladder Preservation ◽  
Cardiovascular Comorbidities ◽  
Grade 3

e16135 Background: Treatment of bladder cancer in elderly patients is a challenging problem because surgery is often not tolerable and the combination of extensive radiotherapy with chemotherapy is also difficult because of patients’ compliance and associated comorbidities. Our study evaluated concurrent radiochemotherapy in elderly patients with locally advanced bladder cancer (T2-T4) in terms of efficacy and tolerability. Methods: Between January 2005 and December 2007, we treated 34 patients with transitional carcinoma of the bladder, with or without nodal involvement, no distant metastases, and median age 79 years (range 66 - 89 years). Their performance status was 0–1-2 in 10–16–8 patients respectively. Cardiovascular comorbidities were the most common (15 patients). The treatment consisted in conformal radiotherapy (mean irradiation dose = 56.4 Gy) concomitant with biweekly Gemcitabine 200 mg/sqm starting on day 1 of radiotherapy. Results: Response was assessed at 4–6 weeks after the end of treatment by cystoscopy with biopsies and MRI. All the patients could end the intended radiation therapy but four of them could not tolerate all the chemotherapy. 13 patients achieved complete response, 12 patients - partial response and 9 patients stable disease. The most common toxicities were: diarrhea (grade 1–2 in 11 patients, grade 3–6 patients), cystitis (grade 1–2 in 5 patients), leucopenia (grade 1–2 in 12 patients, grade 3–4 in 2 patients), thrombocytopenia (grade 1–2 in 6 patients) and anemia (grade 1–2 in 4 patients). Three patient required hospitalization for dehydration and two for febrile neutropenia. After a median follow-up time of 17.4 months, there were 7 relapses and 5 distant metastases. One-year survival rate was 82.41% (28 patients). 6 patients died, 3 from their cancer and 3 from comorbidities. Conclusions: Chemoradiation is well enough tolerated even in elderly patients and also an efficient and organ sparing therapeutic alternative for patients over 65 years old. The treatment choice was based on patients’ preference considering better quality of life with bladder preservation. The use of age-specific therapy adjustments has shown that aggressive treatment for bladder cancer is associated with improved survival even in elderly patients. No significant financial relationships to disclose.

Neoadjuvant chemotherapy for locally advanced cervical cancer: Experience at the Instituto Oncologico Nacional SOLCA Guayaquil.

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. e15571-e15571
Author(s):  
Guillermo Paulson ◽  
Katherine Garcia ◽  
Mayra Santacruz ◽  
Ruth Ginger Engracia ◽  
Jose Francisco Mendoza
Keyword(s):  
Cervical Cancer ◽  
Neoadjuvant Chemotherapy ◽  
Invasive Cervical Cancer ◽  
Locally Advanced ◽  
Progression Free Survival ◽  
Complete Response ◽  
Median Number ◽  
Number Of Cycles ◽  
Clinical Records ◽  
Cancer Experience

e15571 Background: Cervical cancer is the most common malignancy of women in Ecuador. The main problem of concomitant chemo-radiotherapy (CRT) is the delay in starting radiation therapy, economic and logistical problems for high demand in radiotherapy. It has been neoadjuvant chemotherapy (NACT) followed by CRT the main treatment at our center in order to find an alternative to long waits before the start of radiotherapy. The aim of this study was to determine the response to NACT followed by CRT in terms progression-free survival (PFS) and overall survival (OS). Methods: diagnosed with invasive cervical cancer locally advanced stage II-III were analyzed retrospectively reviewed clinical records of pre-existing data from 2008 to 2010. Results: after meeting the criteria of exclusion, leaving 116 cases. The median age: 49 years (range: 28-82 years). The histology was 73% (85) squamous cell carcinoma, 26% (30) adenocarcinoma and 0.9% (1) not specified. Patients with stage IIB: 81.9% (95), IIIA: 10.3% (12), IIIB: 7.8% (9). Of the 116 patients 69% (80) received NACT. The main NACT was paclitaxel 175mg/m2 + Cisplatin 75mg/m2 every 3 weeks 63.8% (74), the remaining group received another protocol, the median number of cycles of NACT was 5 (1 - 8 cycles), the start of radiotherapy since the conclusion of NACT was 53 days on average (1 to 285 days) and the main regimen of CRT concomitant was cisplatin 40mg/m2 weekly 47.5% (38). In the 49 patients who underwent NACT followed by CRT, a radiological study showed, complete response (CR) 38.8% (19), 18.4% partial response (PR) (9), disease progression (DP) 12.2% (6), stable disease (SD) 8.2% (4) and the end of treatment evaluation gynecological was performed and CR was obtained in 59.2% (29). Persistent or progressive disease after treatment was 22.4% (11), recurrence was 12.2% (6), local recurrence 2.0% (1), distant metastasis 10.2% (5). OS of NACT followed by CRT was 93.9% (46) and PFS was 65.3% (32), OS after CR was 96% (25 / 1) and then 91.7% PR (24 / 2) with p: 0.439. Conclusions: NACT followed by CRT is a valid option because it improves disease-related symptoms, but OS did not improve significantly even after CR.

Retrospective review of modified dose docetaxel, cisplatin, and 5-flourouracil (DCF) for the treatment of first-line metastatic gastric carcinomas.

2013 ◽  
Vol 31 (15_suppl) ◽  
pp. e15175-e15175
Author(s):  
Nuriye Özdemir ◽  
Sercan Aksoy ◽  
Tulay Eren ◽  
Huseyin Abali ◽  
Omur Berna Oksuzoglu ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Retrospective Review ◽  
Progression Free Survival ◽  
Complete Response ◽  
Metastatic Gastric Cancer ◽  
Median Number ◽  
Hematological Toxicity ◽  
First Line ◽  
Gastric Carcinomas ◽  
Grade 3

e15175 Background: Docetaxel, cisplatin, and 5FU (DCF) has been shown to be an effective regimen for metastatic gastric carcinomas. However, treatment-related adverse events is quite high with original dose DCF. We evaluated the outcomes of the metastatic gastric carcinomas who treated with modified dose DCF (mDCF) in our institution. Methods: A single institution retrospective review of patients with metastatic gastric cancer treated with three weekly mDCF from 1/2006 to 1/2013 was evaluated. Over this time period a standard order-set was in place in which cisplatin 60 mg/m2, 5FU 600 mg/m2 and docetaxel 60 mg/m2 was given three weekly. Tumor response was calculated retrospectively using RECIST criteria. Results: One hundred and ninety-one patients were included the study. The median age was 55 years (23 to 76), 74% were male, and 82% were chemo-naive. Eighty percent of the patients were metastatic at the time of diagnosis. The median number of cycles administered was 6 (2-10). Hematological toxicity was mild with grade 3/4 granulocytopenia in 25% of the patients, grade 3/4 thrombocytopenia in 4% of the patients, and grade 3/4 anemia in 9% of the patients. Neutropenic infection occurred in 9 (%5) patients. Grade 3/4 nausea/vomiting was reported by 10% of the patients, and diarrhea by 7%. A total of 19 (10%) patients had dose delays or dose reductions related to toxicity. Six (3%) patients had complete response and 43 (23%) patients had partial response. Stable disease were occurred in 83 (45%) patients and 56 (23%) progressive disease. Ninety percent of the patients have died with median follow-up of 8 months. Progression-free survival was 7 months (95% CI 6 to 7.8 m) and overall survival was 10 months (95% CI 8.7 to 11.2 m). Conclusions: mDCF has mild hematological toxicity and overall excellent tolerance in first line metastatic gastric cancer patients. Response rate and the survival of these patients with a minimal toxicity are comparable with the original dose DCF.

REGN2810: A fully human anti-PD-1 monoclonal antibody, for patients with unresectable locally advanced or metastatic cutaneous squamous cell carcinoma (CSCC)—Initial safety and efficacy from expansion cohorts (ECs) of phase I study.

2017 ◽  
Vol 35 (15_suppl) ◽  
pp. 9503-9503 ◽  
Author(s):  
Kyriakos P. Papadopoulos ◽  
Taofeek Kunle Owonikoko ◽  
Melissa Lynne Johnson ◽  
Irene Brana ◽  
Marta Gil-Martin ◽  
...  
Keyword(s):  
Phase 1 ◽  
Locally Advanced ◽  
Standard Of Care ◽  
Initial Response ◽  
Complete Response ◽  
Median Number ◽  
Whole Exome ◽  
Tumor Measurements ◽  
Prior Systemic Therapy ◽  
Grade 3

9503 Background: There is no established standard of care for unresectable locally advanced or metastatic CSCC. UV-induced DNA damage causes hypermutation in most CSCCs. Therefore, these tumors may be responsive to PD-1 checkpoint blockade. In the dose escalation portion of the phase 1 study of REGN2810, a durable (19 + months) radiologic complete response was observed in a patient (pt) with metastatic CSCC (ASCO 2015, #3024). Methods: ECs enrolled pts with distantly metastatic (EC 7) and locally advanced (EC 8) CSCC. All patients received 3 mg/kg REGN2810 by intravenous infusion over 30 minutes every 2 weeks for up to 48 weeks. Research biopsies were performed at baseline and Day 29 (and at progression, if possible). Tumor measurements were performed every 8 weeks according to RECIST 1.1 to determine overall response rate (ORR). Data cutoff date was 31 Jan 2017. Results: 26 pts were enrolled (10 in EC 7 and 16 in EC 8): median age, 72.5 y (range, 56-88y); median PS 1 (range, 0 – 1); 21M:5F; median number of prior systemic therapy regimens, 1 (range, 0 – 2). Median exposure to REGN2810 was 7 doses (range, 1-22). The most common treatment-related adverse event of any grade was fatigue (19.2%). Each of the following ≥ Grade 3 related AEs occurred once: AST elevation, ALT elevation, arthralgia, and rash. ORR (PR + CR, including unconfirmed) and disease control rate (ORR+SD) were 52% (12/23; 4uPR, 5 PR, 2CR, 1 uCR) and 70% (16/23, including 4SD), respectively. Three patients are not yet evaluable. Median PFS and OS have not been reached, and only one patient has experienced PD during REGN2810 treatment after initial response. Correlative studies are in process, including PD-L1 status and whole exome tumor DNA sequencing. Conclusions: REGN2810 is well tolerated and produces antitumor activity in patients with advanced CSCC. A pivotal trial of REGN2810 for patients with advanced CSCC is enrolling patients (NCT02760498). Clinical trial information: NCT02383212.

Cemiplimab (REGN2810): A fully human anti-PD-1 monoclonal antibody for patients with unresectable locally advanced or metastatic cutaneous squamous cell carcinoma (CSCC)—Initial safety and efficacy from expansion cohorts (ECs) of phase I study.

2018 ◽  
Vol 36 (5_suppl) ◽  
pp. 195-195 ◽  
Author(s):  
Kyriakos P Papadopoulos ◽  
Taofeek Kunle Owonikoko ◽  
Melissa Johnson ◽  
Irene Brana ◽  
Marta Gil Martin ◽  
...  
Keyword(s):  
Phase 1 ◽  
Locally Advanced ◽  
Standard Of Care ◽  
Initial Response ◽  
Complete Response ◽  
Median Number ◽  
Whole Exome ◽  
Tumor Measurements ◽  
Prior Systemic Therapy ◽  
Grade 3

195 Background: There is no established standard of care for unresectable locally advanced or metastatic CSCC. UV-induced DNA damage causes hypermutation in most CSCCs. Therefore, these tumors may be responsive to PD-1 checkpoint blockade. In the dose escalation portion of the phase 1 study of cemiplimab (REGN2810), a durable (19 + months) radiologic complete response was observed in a patient (pt) with metastatic CSCC (ASCO 2015, #3024). Methods: ECs enrolled pts with distantly metastatic (EC 7) and locally advanced (EC 8) CSCC. All patients received cemiplimab 3 mg/kg by intravenous infusion over 30 minutes every 2 weeks for up to 48 weeks. Research biopsies were performed at baseline and Day 29 (and at progression, if possible). Tumor measurements were performed every 8 weeks according to RECIST 1.1 to determine overall response rate (ORR). Data cutoff date was 31 Jan 2017. Results: 26 pts were enrolled (10 in EC 7 and 16 in EC 8): median age, 72.5 y (range, 56–88y); median PS 1 (range, 0–1); 21M:5F; median number of prior systemic therapy regimens, 1 (range, 0–2). Median exposure to cemiplimab was 7 doses (range, 1–22). The most common treatment-related adverse event of any grade was fatigue (19.2%). Each of the following ≥ Grade 3 related AEs occurred once: AST elevation, ALT elevation, arthralgia, and rash. ORR (PR + CR, including unconfirmed) and disease control rate (ORR+SD) were 52% (12/23; 4uPR, 5 PR, 2CR, 1 uCR) and 70% (16/23, including 4SD), respectively. Three patients are not yet evaluable. Median PFS and OS have not been reached, and only one patient has experienced PD during cemiplimab treatment after initial response. Correlative studies are in process, including PD-L1 status and whole exome tumor DNA sequencing. Conclusions: Cemiplimab is well tolerated and produces antitumor activity in patients with advanced CSCC. A pivotal trial of cemiplimab for patients with advanced CSCC is enrolling patients. Clinical trial information: NCT02383212.

A Phase I/II Study of the Tolerability of Lenalidomide and Low Dose Dexamethasone in Previously Treated Multiple Myeloma Patients with Impaired Renal Function: Pre1003, a Precog LLC Study

Blood ◽  
2012 ◽  
Vol 120 (21) ◽  
pp. 1856-1856
Author(s):  
Joseph R. Mikhael ◽  
Judith Manola ◽  
Amylou Constance Dueck ◽  
Suzanne R Hayman ◽  
Kurt Oettel ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Overall Survival ◽  
Renal Function ◽  
Renal Insufficiency ◽  
Impaired Renal Function ◽  
Response Rate ◽  
Progression Free Survival ◽  
Free Survival ◽  
Previously Treated ◽  
Grade 3

Abstract Abstract 1856 Background: Lenalidomide has proven to be a highly effective treatment in relapsed multiple myeloma (MM), particularly when used in combination with dexamethasone. However, over 30% of patients with myeloma have renal insufficiency and as lenalidomide is renally excreted, little information is available about its use in myeloma patients with impaired kidney function. Defining a safe and effective dose of lenalidomide in this context is critical. Objective: We undertook this study to establish the maximum tolerated dose of lenalidomide in three cohorts of patients with different levels of impaired renal function: Group A - patients with creatinine clearance (CrCl) between 30 and 60 mL/min, Group B - patients with CrCl <30 mL/min not on dialysis, and Group C - patients with CrCl < 30mL/min who are on dialysis. Secondary endpoints included response rate, progression free survival and overall survival. Methods: Eligible patients had previously treated MM with renal impairment defined as creatinine clearance < 60 mL/min measured within 21 days prior to registration. Patients previously treated with lenalidomide were required to demonstrate clinical response (any duration) or stable disease with progression-free interval of > 6 months from start of that therapy. All patients received dexamethasone 40 mg orally on days 1, 8, 15 and 22 of a 28-day cycle. Prophylactic anticoagulation consisted of either 81 mg or 325 mg per day of aspirin. Patients also received lenalidomide orally every 1 or 2 days on days 1 through 21 of a 28-day cycle, as described below (Table 1). Starting doses were as in US Product Insert. Dose escalation follows a standard 3+3 design. Results: There have been 23 patients enrolled into groups and cohorts as shown in Table 1. Median age was 73 (range 49–89) and 13 (57%) were women. ISS stage was advanced in all patients, 0 in stage 1, 4 (18%) in stage 2 and 19 (82%) in stage 3. The regimen was well tolerated. Indeed, the MTD has not been reached in any of the groups, as no DLTs have occurred to date. The most commonly reported clinical adverse events (all grades, independent of attribution) across all patients included infections, hyperglycemia, constipation, dizziness, hyponatremia, hypocalcemia and tremor. Hematological toxicities (grade 3–4) occurred in 13 out of 21 pts (62%), mostly neutropenia and thrombocytopenia. Grade 3–4 events at least possibly related to the regimen occurred in 70% and included pneumonia (26%) and otitis media (9%). Response was seen in 14 patients, resulting in an overall response rate of 61%. CR was seen in 1 patient (4%), VGPR in 2 patients (9%), PR in 11 patients (43%), and SD for 9 patients. With median follow-up of 15.5 months, median progression-free survival is 9.8 months and median overall survival is 22 months. Conclusion: Lenalidomide and dexamethasone is a safe and effective regimen in patients with multiple myeloma and renal insufficiency. It is also very well tolerated, although cytopenias are common but manageable. MTD has yet to be reached in each group, allowing for higher doses to be given than previously thought, including 25mg daily (for 21/28 days) in patients with CrCl 30–60 mL/min, 25 mg every other day (for 21/28 days) in patients with CrCl < 30 mL/min not on dialysis, and 10mg daily (for 21/28 days) in patients with CrCl < 30 mL/min on dialysis. These results will provide needed, clinically relevant dosing for lenalidomide in MM patients with renal insufficiency. Disclosures: Kaufman: Millenium: Consultancy; Onyx: Consultancy; Celgene: Consultancy; Novartis: Consultancy.

Adjuvant Cisplatin Plus Methotrexate Versus Methotrexate, Vinblastine, Epirubicin, and Cisplatin in Locally Advanced Bladder Cancer: Results of a Randomized, Multicenter, Phase III Trial (AUO-AB 05/95)

2005 ◽  
Vol 23 (22) ◽  
pp. 4963-4974 ◽  
Author(s):  
Jan Lehmann ◽  
Margitta Retz ◽  
Christina Wiemers ◽  
Joachim Beck ◽  
Joachim Thüroff ◽  
...  
Keyword(s):  
Bladder Cancer ◽  
Radical Cystectomy ◽  
Locally Advanced ◽  
Transitional Cell ◽  
Progression Free Survival ◽  
Phase Iii ◽  
Who Grade ◽  
Free Survival ◽  
Advanced Bladder Cancer ◽  
Grade 3

Purpose Radical cystectomy as standard treatment of muscle-invasive urothelial carcinoma of the urinary bladder cures less than 50% of patients with locally advanced bladder cancer. We compared two adjuvant combination chemotherapies in patients with stage pT3a-4a and/or pathologic node-positive transitional-cell carcinoma of the bladder after radical cystectomy. Patients and Methods A total of 327 patients were randomly assigned to either adjuvant systemic chemotherapy with three cycles of cisplatin 70 mg/qm2 on day 1 and methotrexate 40 mg/qm2 on days 8 and 15 of a 21-day cycle (CM) or three cycles of methotrexate 30 mg/qm2 on days 1, 15, and 22, vinblastine 3 mg/qm2 on days 2, 15, and 22, epirubicin 45 mg/qm2 on day 2, and cisplatin 70 mg/qm2 on day 2 of a 28-day cycle (M-VEC). Results The hazard ratio for progression-free survival as the primary end point was 1.13 (90% CI, 0.86 to 1.48) for 163 CM patients compared with 164 M-VEC patients whose right-hand limit remained below the upper bound compatible with the noninferiority hypothesis (α = .0403). The 5-year progression-free, tumor-specific, and overall survival rates (point estimates ± SE) for CM versus M-VEC were 46.3% ± 4.6% v 48.8% ± 4.5%, 52.0% ± 4.6% v 52.3% ± 4.8%, and 46.1% ± 4.3% v 45.1% ± 4.6%, respectively. WHO grade 3 and 4 leukopenia occurred in 7.0% of patients treated with CM and 22.2% of patients treated with M-VEC (P < .0001). Conclusion CM cannot be considered inferior to M-VEC with regard to progression-free survival of patients with locally advanced bladder cancer after radical cystectomy. Moreover, patients receiving adjuvant CM combination therapy experienced significantly less grade 3 and 4 leukopenia than patients treated with M-VEC.

scholarly journals ML-21 Tirabrutinib monotherapy for relapsed/refractory primary central nervous system lymphoma

2020 ◽  
Vol 2 (Supplement_3) ◽  
pp. ii18-ii18
Author(s):  
Keiichi Kobayashi ◽  
Nobuyoshi Sasaki ◽  
Kuniaki Saito ◽  
Yuki Yamagishi ◽  
Yoshie Matsumoto ◽  
...  
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Central Nervous System Lymphoma ◽  
Whole Brain Radiotherapy ◽  
Progression Free Survival ◽  
Standard Of Care ◽  
Complete Response ◽  
Cell Receptor ◽  
Median Number ◽  
Grade 3

Abstract Backgrounds & purpose: Prognosis of patients with primary central nervous system lymphoma (PCNSL) remains poor despite multiagent immunochemotherapy, and standard of care for relapsed or refractory (r/r) PCNSL has not been established. Recent progresses on molecular genetics and biology of PCNSL have led to development of novel molecular targeted therapies, especially targeting Bruton’s tyrosine kinase (BTK), located in the B-cell receptor and Toll-like receptor signaling pathways. Tirabrutinb, a second generation BTK inhibitor, was approved for r/rPCNSL in March 2020 in Japan. Methods: Patients with r/rPCNSL treated with tirabrutinib since December 2017 were eligible for this retrospective study. Tirabrutinib was given orally at doses 320–480 mg/day daily until progression or unacceptable toxicity. Results: A total of 7 patients were enrolled (6 relapses, 1 refractory), 4 males, median age was 73 (range, 54–80 years), and median KPS was 70 (70–90). Three patients had received prior whole brain radiotherapy. Median number of prior therapies was 1 (1–2). Best overall response rate was 57.1%; 42.9% with a complete response (CR/CRu), 14.3% with a partial response (PR), while there were 3 PDs (42.9%). Four patients experienced PD and estimated median progression-free survival (mPFS) was 29.6 months. All patients were alive at the data cutoff with median follow up of 21.4 months (2–30.4). Common adverse events (AEs) include grade 4 neutropenia (n=1), grade 3 lymphopenia (n=3), and hepatic dysfunction (n=1). Toxic rash was observed in four patients (grade 3 in one, grade 2 in three) leading to discontinuation of tirabrutinib in two patients, while others continued on TIR with dose reduction and steroid use. The median time to rash presentation was 28 days (12–28). Conclusions: Tirabrutinib was well tolerated with frequent minor to moderate skin rash emerging within one month and active for r/rPCNSL. Long-term efficacy and safety profile need to be determined with a larger cohort.

Phase II randomized trial of radiotherapy (RT), cetuximab (E), and pemetrexed (Pem) with or without bevacizumab (B) in locally advanced squamous cell carcinoma of the head and neck (SCCHN).

2013 ◽  
Vol 31 (15_suppl) ◽  
pp. 6043-6043 ◽  
Author(s):  
Athanassios Argiris ◽  
James Ohr ◽  
Greg J. Kubicek ◽  
Uma Duvvuri ◽  
Dwight Earl Heron ◽  
...  
Keyword(s):  
Phase Ii ◽  
Performance Status ◽  
Locally Advanced ◽  
Stage Iv ◽  
Progression Free Survival ◽  
Median Number ◽  
Stage Iii ◽  
Community Practice ◽  
History Of ◽  
Grade 3

6043 Background: We previously developed a novel regimen by the addition of Pem to RT and E (Ann Oncol 2011;22:2482). The current study evaluated PemE in the phase II setting and assessed the addition of B, an anti-VEGF monoclonal antibody, to PemE based on promising data with Pem/B (JCO 2011;29:1140) and E/B (Ann Oncol 2013;24:200) in recurrent/metastatic SCCHN. Methods: Patients (pts) with previously untreated stage III/IV SCCHN of the oropharynx, larynx or hypopharynx, performance status (PS) 0-1, no history of bleeding, and adequate laboratory parameters were randomized after stratification for PS, stage and site to: RT 2 Gy/day to 70Gy, E 250mg/m2 weekly, after a loading dose of 400 mg/m2 1 week prior starting RT, and Pem 500mg/m2 every 21 days x 3 cycles (arm A, PemE), or the same regimen plus B 15mg/kg every 21 days x 3 cycles during RT followed by B maintenance x 8 cycles (arm B, B-PemE), with antibiotic prophylaxis. The primary endpoint was progression-free survival (PFS) with a target of 64% at 2 years; planned sample size was 80. Results: 79 pts were randomized of whom 77 were eligible and analyzable (arm A/B:36/41); oropharynx 65/larynx 12; HPV+ 38/HPV- 15/HPV unknown 24; stage IV 54/stage III 23. 31 pts were enrolled in community centers. Treatment delivery of E and Pem was similar between arms: E, median number of doses 8 (range, 5-11); Pem 3 (2-3); and B 3 (1-3). 5 deaths occurred: 3 due to progression; 1 from unknown cause; 1 pt died from hemoptysis after bronchoscopy within 4 weeks of the 8th cycle of B leading to elimination of B maintenance after the 6th pt was enrolled. 9 pts (2 HPV+) progressed. With a median follow-up of 18 months, the 2-year PFS was 81% vs 87% and the 2-year overall survival (OS) was 96% vs 86% for arm A vs B. Grade 3/4 acute toxicities for arm A vs B (N=59) : dermatitis 3/1 vs 4/1; mucositis 13/2 vs 13/0; neutropenia 7/4 vs 7/3; rash 6/1 vs 8/1; fatigue 1/0 vs 3/0; weight loss 2/0 vs 5/0. Conclusions: Both regimens are feasible in academic and community practice settings with expected toxicities. Preliminary efficacy results are very promising and better than projected, however, the addition of B does not appear to improve outcomes. Clinical trial information: NCT00703976.

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