Patient controlled analgesia (PCA) vs non-PCA intravenous hydromorphone titration for severe cancer pain: A multi-center, phase III trial, HMORCT09-1.

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. 12078-12078
Author(s):  
Rongbo Lin ◽  
Sunzhi Lin ◽  
Jinfeng Zhu ◽  
Shuitu Feng ◽  
Qingyi Wu ◽  
...  
Keyword(s):  
Cancer Pain ◽  
Phase Iii ◽  
Opioid Tolerance ◽  
Phase Iii Trial ◽  
Adequate Pain Relief ◽  
Median Dosage ◽  
Continuous Dose ◽  
Study Sites ◽  
Acceptable Side ◽  
Clinical Trial Information

12078 Background: The titration of opioid dosage is necessary for adequate pain relief with acceptable side effects among individuals with cancer pain. The titration process can be achieved by non-patient administration or PCA pump. The aim of this study was to evaluate the efficacy of PCA versus non-PAC titration for severe cancer pain. Methods: Patients with severe cancer pain (NRS ≥ 7/10 at rest) were randomized into PCA or non-PCA titration and stratified by opioid tolerance or intolerance. For PCA, the pump was set as no continuous dose, hydromorphone bolus dose was 10%-20% of the total equianalgesic of past 24h for opioid tolerance, or 0.5 mg for opioid intolerance. The lockout time was 15 min. For non-PCA, initial hydromorphone bolus was the same with PCA. Reassess pain at 15 min. The dose of hydromorphone was increased by 50%-100% if pain unchanged or increased, or repeated if NRS was 4-6, or continue at current dose as needed if NRS≤3. The primary endpoint was the time to successful titration (TST) - time from start to the time of pain controlled at NRS ≤ 3 in two consecutive evaluation with 15-min intervals, which was tested by K-M curve. Results: A total of 214 patients were randomized (106 in PCA, 108 in non-PCA) in 17 study sites. The most common sites of primary cancer were lung (21.03%), stomach (15.89%), colorectal (14.49%) etc. Median TSTs were 0.50h in PCA, 0.79h in non-PCA, HR 1.64 (95% CI 1.23, 2.17, P = 0.00127). In opioid tolerance, 0.50h in PCA, 1.00h in non-PCA (HR 1.92, 95% CI 1.32, 2.78, P = 0.0025). while in opioid intolerance, 0.50h in PCA and 0.50 in non-PCA (HR 1.35, 95% CI 0.88, 2.04, P = 0.162). The median dosage of hydromorphone for TST was 1.00mg (P25, P75 0.50, 2.00) in PCA, 1.50mg (P25, P75 1.00, 2.50) in non-PCA (P = 0.086). In opioid tolerance, 1.00mg (P25, P75 1.00, 2.00) in PCA, 2.00mg (P25, P75 1.00, 4.00) in non-PCA (P = 0.009). In opioid intolerance, 1.00mg (P25, P75 0.50, 2.00) in PCA and 1.00 mg (P25, P75 0.50, 2.00) non-PCA (P = 0.793). Mean patient satisfaction assessed by ESAS score was significantly superior in PCA to non-PCA (0.62±0.67 vs 1.27±0.98 for ITT, 0.66±0.66 vs 1.39±1.00 for opioid tolerance, and 0.56±0.69 vs 1.13±0.95 for opioid intolerance). Adverse events were similar in both PCA/non-PCA groups. Conclusions: PCA IV hydromorphone titration provided quicker analgesic effect, higher patients satisfaction, and a similar tolerability as compared to non-PCA administration in patients with severe cancer pain. Clinical trial information: NCT03375515 .

scholarly journals Comparing Patient-Controlled Analgesia Versus Non-PCA Hydromorphone Titration for Severe Cancer Pain: A Randomized Phase III Trial

2021 ◽  
pp. 1-8
Author(s):  
Rongbo Lin ◽  
Sunzhi Lin ◽  
Shuitu Feng ◽  
Qingyi Wu ◽  
Jianqian Fu ◽  
...  
Keyword(s):  
Cancer Pain ◽  
Bolus Dose ◽  
Rating Scale ◽  
Numeric Rating Scale ◽  
Phase Iii ◽  
Patient Controlled Analgesia ◽  
Phase Iii Trial ◽  
Continuous Dose ◽  
First Occurrence ◽  
Numeric Rating

Background: Opioid titration is necessary to achieve rapid, safe pain relief. Medication can be administered via patient-controlled analgesia (PCA) or by a healthcare provider (non-PCA). We evaluated the efficacy of intravenous PCA versus non-PCA hydromorphone titration for severe cancer pain (≥7 at rest on the 11-point numeric rating scale [NRS]). Patients and Methods: Patients with severe cancer pain were randomized 1:1 to PCA or non-PCA titration, stratified by opioid-tolerant or opioid-naïve status. The PCA pump was set to no continuous dose, with a hydromorphone bolus dose 10% to 20% of the total previous 24-hour equianalgesic (for opioid-tolerant patients) or 0.5 mg (for opioid-naïve patients). For the non-PCA group, the initial hydromorphone bolus dose was identical to that in the PCA group, with the subsequent dose increased by 50% to 100% (for NRS unchanged or increased) or repeated at the current dose (for NRS 4–6). Hydromorphone delivery was initiated every 15 minutes (for NRS ≥4) or as needed (for NRS ≤3). The primary endpoint was time to successful titration (TST; time from first hydromorphone dose to first occurrence of NRS ≤3 in 2 consecutive 15-minute intervals). Results: Among 214 patients (PCA, n=106; non-PCA, n=108), median TSTs (95% CI) were 0.50 hours (0.25–0.50) and 0.79 hours (0.50–1.42) for the PCA and non-PCA groups, respectively (hazard ratio [HR], 1.64; 95% CI, 1.23–2.17; P=.001). TSTs in opioid-tolerant patients were 0.50 hours (0.25–0.75) and 1.00 hours (0.50–2.00) for the PCA and non-PCA groups, respectively (HR, 1.92; 95% CI, 1.32–2.78; P=.003); in opioid-naive patients, TST was not significantly different for the PCA versus non-PCA groups (HR, 1.35; 95% CI, 0.88–2.04; P=.162). Pain score (median NRS; interquartile range) over 24 hours was significantly lower in the PCA group (2.80; 2.15–3.22) than in the non-PCA group (3.00; 2.47–3.53; P=.020). PCA administration produces significantly higher patient satisfaction with pain control than non-PCA administration (P<.001). Conclusions: Intravenous hydromorphone titration for severe cancer pain was achieved more effectively with PCA than with non-PCA administration.

Sustainability of antiemetic responses with APF530 (sustained-release granisetron) during multiple cycles of moderately (MEC) and highly (HEC) emetogenic chemotherapy regimens: Results of a randomized phase III trial.

2013 ◽  
Vol 31 (15_suppl) ◽  
pp. 9626-9626
Author(s):  
Ralph V. Boccia ◽  
William Cooper ◽  
Erin O'Boyle
Keyword(s):  
Rescue Medication ◽  
Emetogenic Chemotherapy ◽  
Phase Iii ◽  
Sustained Delivery ◽  
Test Results ◽  
Phase Iii Trial ◽  
Multiple Cycles ◽  
To Receive ◽  
Delayed Phase ◽  
Clinical Trial Information

9626 Background: Patients receiving MEC or HEC were administered subcutaneous (SC) APF530 500 mg, a sustained delivery formulation of granisetron (10 mg). The complete antiemetic response rates (CR; no emetic episodes and no rescue medication) were non-inferior to those of palonosetron in preventing acute and delayed chemotherapy-induced nausea and vomiting (CINV) (Grous et al. ASCO 2009, #9627). We report on sustainability of CR with APF530 (10 mg) during multiple chemotherapy cycles in this study. Methods: 1428 patients scheduled to receive single doses of MEC or HEC were randomized to APF530 SC (5 or 10 mg granisetron) or 0.25 mg palonosetron intravenously (IV) prior to cycle 1 (C1). In C2-4, patients who received palonosetron in C1 were randomized to APF530 5 or 10 mg; those who received APF530 continued with their C1 APF530 dose. Treatment cycles were separated by 7-28 days. CR rates were compared between cycles using McNemar’s test. Results: No significant differences in within-cycle CR occurred between APF530 doses during acute and delayed phases in C2-4 for MEC and HEC, but a trend toward higher CR rates was seen in successive cycles. For the 2 doses, CR was sustained across all 4 cycles in 56.5-62.6% and 68.4-71.7% in acute phase, and 41.8-42.4% and 57.5-57.9% in delayed phase with MEC and HEC, respectively. Examination of CR rates in C2, C3, or C4 compared with the rate in C1 showed that CR rates were sustained and that the proportion of patients with no CR in C1 but CR in later cycles was consistently higher than that of patients with CR in C1 but no CR later. For illustration, the table shows C4 CR and C1 CR for patients who received APF530 10 mg in C1 and C4. Conclusions: CR rates achieved with APF530 during acute and delayed phases of CINV in MEC and HEC were maintained over multiple cycles. Clinical trial information: NCT00343460. [Table: see text]

Lenalidomide (LEN)-melphalan-prednisone induction followed by LEN maintenance (MPR-R) in newly diagnosed multiple myeloma (NDMM) elderly patients (Pts) with moderate renal impairment (RI): MM-015 trial post-hoc analysis.

2013 ◽  
Vol 31 (15_suppl) ◽  
pp. 8544-8544
Author(s):  
John V. Catalano ◽  
Antonio Palumbo ◽  
Katja C. Weisel ◽  
Meletios A. Dimopoulos ◽  
Michel Delforge ◽  
...  
Keyword(s):  
Phase Iii ◽  
Newly Diagnosed ◽  
Efficacy And Safety ◽  
Pivotal Phase ◽  
Phase Iii Trial ◽  
Post Hoc Analysis ◽  
Negative Prognostic Factor ◽  
Starting Dose ◽  
Post Hoc ◽  
Clinical Trial Information

8544 Background: The MM-015 pivotal phase III trial showed significant PFS benefit for MPR-R (31 mos) vs. MPR (14 mos) or MP (13 mos; both p < 0.001) followed by placebo in NDMM pts aged ≥ 65 years. As NDMM pts with RI have poor prognosis, this retrospective analysis studied the efficacy and safety of MPR-R in pts with creatinine clearance (CrCl) < 60 mL/min. Methods: LEN starting dose for induction/maintenance was 10 mg/day (D1–21 of a 28-day cycle). Dose adjustments were not recommended for pts with RI. CrCl was calculated using the Cockcroft-Gault equation. Pts with severe RI (serum Cr > 2.5 mg/dL [221 μmol/L]) were excluded from the trial. Results: Pts with CrCl < 60 mL/min (median 47, interquartile range [IQR] 38–55) were included in this analysis: 51% MPR-R, 45% MPR, and 49% MP. Median PFS was significantly higher with MPR-R (26 mos [95% CI 14–48]) vs. MPR (13 mos [95% CI 12–15]) or MP (14 mos [95% CI 12–16]; both p < 0.001). In a Cox proportional model of PFS, CrCl < 60 mL/min was not identified as a negative prognostic factor (p = 0.69). The most common Gr 4 adverse events (AEs) were hematologic and occurred predominantly during induction and are shown in the Table for pts with or without moderate RI. The number of deaths on study was similar: 10% (MPR-R), 7% (MPR), and 8% (MP); deaths associated with RI or disease progression were reported in ≤ 1% of pts with RI across the arms. Conclusions: The benefit of continuous LEN treatment with MPR-R is not compromised in NDMM pts with moderate RI, consistent with the overall trial results. CrCl and AEs should be monitored closely in this population. Clinical trial information: NCT00405756. [Table: see text]

Carfilzomib, lenalidomide, and dexamethasone (KRd) versus bortezomib, lenalidomide, and dexamethasone (VRd) for initial therapy of newly diagnosed multiple myeloma (NDMM): Results of ENDURANCE (E1A11) phase III trial.

2020 ◽  
Vol 38 (18_suppl) ◽  
pp. LBA3-LBA3 ◽  
Author(s):  
Shaji Kumar ◽  
Susanna J. Jacobus ◽  
Adam D. Cohen ◽  
Matthias Weiss ◽  
Natalie Scott Callander ◽  
...  
Keyword(s):  
Progression Free Survival ◽  
Initial Therapy ◽  
Phase Iii ◽  
Phase Ii Trials ◽  
Phase 3 ◽  
Phase Iii Trial ◽  
Free Survival ◽  
Induction Regimen ◽  
To Receive ◽  
Clinical Trial Information

LBA3 Background: Bortezomib (btz) combined with lenalidomide (len) and dexamethasone (dex) (VRd) is a standard initial therapy for NDMM. Carfilzomib (cfz), a next-generation proteasome inhibitor, in combination with len-dex (KRd) has shown higher efficacy in phase II trials. This randomized phase III trial was designed to examine if KRd improves progression free survival (PFS) compared to VRd in NDMM (current results), and whether indefinite maintenance with len improves OS compared with two-year maintenance (to be analyzed once data matures). Methods: Patients (Pts) with NDMM, were randomized to receive VRd or KRd in a 1:1 fashion for 36 weeks followed by a second randomization (1:1) to indefinite versus two years of len maintenance. Pts without del17p, t (14;16), t(14;20), plasma cell leukemia or high-risk GEP70 profile, were enrolled. VRd arm included btz 1.3 mg/m2 on days(d) 1, 4, 8, and 11 (d 1, 8 for cycles 9-12), len 25 mg d 1-14, and dex 40 mg d 1, 2, 4, 5, 8, 9, 11, 12 of a 3-week (wk) cycle for 12 cycles, while pts in the KRd arm received cfz 36 mg/m2 d 1, 2, 8, 9, 15, 16 with len 25 mg daily on d 1-21 and dex 40 mg wkly, in 4 wk cycles for 9 cycles. Maintenance included len 15mg d 1-21 every 4 wks. The study was designed to detect a hazard ratio (HR)=0.75 with 80% power at 1-sided 2.5% alpha and 399 PFS events (progression or death regardless of intervening therapy). Results: The study accrued 1087 pts (VRd=542, KRd=545). The median age was 65y. Treatment, efficacy, and toxicity data are in the table. At the second of 3 planned interim analyses, with PFS HR=1.04 (95% CI, 0.8 to 1.3, p=0.74), futility was met. Median PFS was VRd=34.4m and KRd=34.6m; no differences were seen based on age (<65 or ≥65), presence or absence of t(4;14) or ISS stage. The three-year OS (95% CI) was similar: VRd 84% (80 to 88) and KRd 86% (82 to 89). Conclusions: In this randomized phase 3 trial, KRd did not improve PFS compared with VRd in NDMM. A significantly higher rate of cardio-pulmonary and renal toxicity was observed with KRd, while neuropathy rates were higher with VRd. VRd remains the standard triplet induction regimen in standard and intermediate risk NDMM, and a suitable backbone for 4 drug combinations. Clinical trial information: NCT01863550 . [Table: see text]

Recovery of complete antiemetic response with APF530 during treatment with moderately (MEC) and highly (HEC) emetogenic chemotherapy regimens in patients who failed palonosetron.

2013 ◽  
Vol 31 (15_suppl) ◽  
pp. e20569-e20569 ◽  
Author(s):  
Roberto Arevalo-Araujo ◽  
Erin O'Boyle ◽  
William Cooper ◽  
Paul Alexander Robertson
Keyword(s):  
Clinical Trial ◽  
Rescue Medication ◽  
Complete Response ◽  
Emetogenic Chemotherapy ◽  
Phase Iii ◽  
Sustained Delivery ◽  
Acute Setting ◽  
Phase Iii Trial ◽  
Using Data ◽  
Clinical Trial Information

e20569 Background: Several 5-HT3 antagonists are available to prevent chemotherapy-induced nausea and vomiting (CINV); when control is inadequate with one agent, another may be used. Using data from a randomized phase III trial (Grous et al. ASCO 2009, #9627), we examined the efficacy of APF530, a sustained delivery formulation of the 5-HT3antagonist granisetron, in patients (pts) who failed to achieve a complete response (CR; no emesis or rescue medication) with palonosetron (PALO) in preventing acute (0-24 h) and delayed (24-120 h) CINV in pts receiving MEC or HEC. Methods: 1,428 pts receiving single doses of MEC or HEC were randomized to APF530 250 mg (5 mg granisetron) subcutaneously (SC), APF530 500 mg (10 mg granisetron) SC, or PALO 0.25 mg intravenously (IV) in cycle 1 (C1). Prior to C2, pts who received PALO in C1 and remained on study were re-randomized to APF530 250 mg or 500 mg SC. CR rates in C2 were assessed for pts receiving APF530 500 mg who did not achieve CR in C1 with PALO. Results: 446 pts received PALO in C1 (208 MEC; 238 HEC). Of these, 194 (43.5%) were overall (0-120 h) failures (100/208 [48.1%] MEC; 94/238 [39.5%] HEC). Of 194 C1 PALO failures, 72 were re-randomized prior to C2 to APF530 500 mg (38 MEC; 34 HEC). Of 38 MEC PALO failures who received APF530 in C2, overall CR was 39.5% (57.9% acute; 38.2% delayed). Of 34 HEC PALO failures who received APF530 in C2, overall CR was 41.2% (58.3% acute; 45.5% delayed). In the acute phase, > 50% of MEC and HEC pts who failed PALO in C1 achieved CR to APF530 500 mg in C2. CR rate for pts receiving MEC or HEC was slightly less in the delayed vs acute setting. Conclusions: APF530 500 mg demonstrated substantial activity (ie, CR) in pts receiving MEC or HEC who had failed PALO in C1. Failure to achieve an initial CR to PALO 0.25 mg IV does not predict failure of APF530 500 mg SC in subsequent MEC or HEC cycles. Further studies are needed to confirm these observations. Clinical trial information: NCT00343460. [Table: see text]

Prior and concurrent use of abiraterone and enzalutamide with Ra-223 in an expanded access setting.

2015 ◽  
Vol 33 (7_suppl) ◽  
pp. 253-253 ◽  
Author(s):  
A. Oliver Sartor ◽  
Daniel Celestino Fernandez ◽  
Michael J. Morris ◽  
Andrei Iagaru ◽  
Alan Brown ◽  
...  
Keyword(s):  
Standard Of Care ◽  
Phase Iii ◽  
Phase Iii Trial ◽  
Early Access ◽  
Concurrent Use ◽  
The Us ◽  
Grade 3 ◽  
Access Program ◽  
Clinical Trial Information

253 Background: The aim of this prospective early-access program (EAP) was to monitor acute and long-term safety of Ra-223 CL2. The ALSYMPCA RA-223 phase III trial was completed prior to abiraterone (Abi) and enzalutamide (Enza) approval. Herein we provide experience with RA-223 in relationship to Abi and Enza. Methods: Symptomatic bone metastatic CRPC pts in the US who were ineligible for or had prior docetaxel were enrolled. Treatment included Ra-223 50 kBq/kg IV q4weeks for 6 cycles concomitant with standard of care medications. Analyses were conducted to assess safety and overall survival (OS) in pts with prior and concurrent Abi and Enza. Results: Of 184 treated, 120 (65%) had prior and 35 (19%) pts had concurrent Abi; 59 (32%) had prior and 25 (14%) pts had concurrent Enza. Baseline characteristics were generally balanced in the overall and across prior and concurrent groups. Pts with no concurrent Abi or Enza had a similar OS to the overall group (Abi 16m, Enza 17m, overall 17m). Due to a small number of events (7 Abi, 6 Enza), a median value was not calculated for the concurrent groups. 8 deaths occurred during treatment none were related to RA-223. The rate of Grade 3-5 AEs was similar across concurrent (Abi 37%, Enza 36%) and prior groups (Abi 43%, Enza 42%) vs overall 41%. Most frequently occurring Gr 3-4 events were anemia (Abi 17%, Enza 8%, overall 11%), thrombocytopenia (Abi 6%, overall 3%), and back pain (Enza 8%, overall 4%). Conclusions: In this EAP, Ra-223 concurrently administered with either abiraterone or enzalutamide was safe and well tolerated adding important information on concurrent use of RA-223 and hormonal agents. Clinical trial information: NCT01516762. [Table: see text]

Patient reported outcomes following palliative gastric RadiOtherapy for symptomatic advanced gastric cancer (PROG): Results from a phase 2 trial.

2017 ◽  
Vol 35 (15_suppl) ◽  
pp. e21667-e21667
Author(s):  
Jeremy Chee Seong Tey ◽  
Huili Zheng ◽  
Yu Yang Soon ◽  
Wee Yao Koh ◽  
Cheng Nang Leong ◽  
...  
Keyword(s):  
Patient Reported Outcomes ◽  
Locally Advanced ◽  
Significant Proportion ◽  
Phase Iii ◽  
Phase Iii Trial ◽  
Phase 2 Trial ◽  
Pain Subscale ◽  
Patient Reported ◽  
The Mean ◽  
Clinical Trial Information

e21667 Background: To determine the effect of gastric radiotherapy (RT) on patient reported outcomes (PROs; secondary endpoint) in the PROG trial. Methods: Patients with symptomatic locally advanced or metastatic gastric carcinoma with at least one index symptom of bleeding, pain or obstruction were treated with palliative gastric radiotherapy to a dose of 36Gy in 12 fractions (at 3Gy daily fractions). PROs were assessed using the European Organisation for Research and Treatment of Cancer Qualify of Life Questionanaire-C30 and stomach module STO22. The primary PRO hypothesis was that at least 30% of patients will achieve a > 10 point absolute improvement (considered significant) in the fatigue, nausea/vomiting and pain subscales in the C30, and dysphagia and pain subscales in the STO22 at 12 fractions and one month after radiotherapy. Assessments were performed at baseline, 12 fractions and one month post radiotherapy. Paired T test was used to compare the mean scores from baseline, and at 12 fractions and one month post completion of RT Results: Questionnaires were available from 49 of 50 patients (98%) at baseline, 36 of 45 patients (80%) at 12 fractions and 16 of 38 patients (42%) at one-month post RT. At 12 fractions, 50%, 28% and 44% of patients achieved a significant improvement in fatigue, nausea/vomiting and pain subscales in the C30 respectively. 42% and 28% of patients achieved a significant improvement in dysphagia and pain subscale in the STO22. The observed mean difference was 11 points and 4 points for pain subscale in the C30 and STO22 (P < 0.02). At one-month post RT, 63%, 31% and 50% of patients achieved a significant improvement in fatigue, nausea/vomiting and pain subscales in the C30 respectively. 44% and 19% of patients achieved a significant improvement in dysphagia and pain subscale in the STO22. There were no significant differences in the mean scores in the subscales of interest. Conclusions: Palliative gastric radiotherapy resulted in improvements in fatigue, dysphagia and pain at 12 fractions and at 1-month post radiotherapy in a significant proportion of patients. A phase III trial comparing the effects of different fractionation regimens on PROs is warranted. Clinical trial information: NCT01341756.

Clinical Benefit With Docetaxel Plus Fluorouracil and Cisplatin Compared With Cisplatin and Fluorouracil in a Phase III Trial of Advanced Gastric or Gastroesophageal Adenocarcinoma: The V-325 Study Group

2007 ◽  
Vol 25 (22) ◽  
pp. 3205-3209 ◽  
Author(s):  
Jaffer A. Ajani ◽  
Vladimir M. Moiseyenko ◽  
Sergei Tjulandin ◽  
Alejandro Majlis ◽  
Manuel Constenla ◽  
...  
Keyword(s):  
Weight Loss ◽  
Cancer Pain ◽  
Clinical Benefit ◽  
Karnofsky Performance Status ◽  
Performance Status ◽  
Life Time ◽  
Clinic Visit ◽  
Phase Iii ◽  
Phase Iii Trial ◽  
Free Survival

Purpose For patients with advanced gastric or gastroesophageal cancer (AGGEC) providing clinical benefit with improved palliation is highly desirable. However, a prospective evaluation of clinical benefit in AGGEC patients has never before been reported in a phase III setting. Patients and Methods In a multinational trial (V325), 445 patients were randomly assigned and treated with either docetaxel plus cisplatin and fluorouracil (DCF) or cisplatin and fluorouracil (CF). Clinical benefit was prospectively evaluated in this trial as a secondary end point. The primary measure for clinical benefit analysis was time to definitive worsening by one or more categories of Karnofsky performance status (KPS). Secondary clinical benefit end points included time to 5% definitive weight loss, time to definitive worsening of appetite by one grade, pain-free survival (defined as time to first appearance of pain), and time to first cancer pain-related opioid intake. Clinical benefit assessments were recorded at each clinic visit. Results Clinical benefit assessments were performed in more than 75% of patients throughout V325. DCF significantly prolonged time to definitive worsening of KPS compared with CF (median, 6.1 v 4.8 months; hazard ratio, 1.38; 95% CI, 1.08 to 1.76; log-rank P = .009). Although time to definitive weight loss and time to definitive worsening of appetite favored DCF, the results were not statistically significant. Pain-free survival and time to first cancer pain-related opioid intake were comparable. Conclusion To our knowledge, V325 is the first phase III trial to report clinical benefit in AGGEC patients. Clinical benefit was assessed beyond protocol-specific chemotherapy. The addition of D to CF not only significantly improved clinical benefit but also improved quality of life, time to progression, and overall survival compared with CF.

Optimizing chemotherapy for frail and elderly patients (pts) with advanced gastroesophageal cancer (aGOAC): The GO2 phase III trial.

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. 4006-4006 ◽  
Author(s):  
Peter S Hall ◽  
Daniel Swinson ◽  
Justin S. Waters ◽  
Jonathan Wadsley ◽  
Stephen Falk ◽  
...  
Keyword(s):  
Dose Level ◽  
Phase Iii ◽  
Optimum Dose ◽  
Baseline Assessment ◽  
Gastroesophageal Cancer ◽  
Treatment Utility ◽  
Phase Iii Trial ◽  
Dose Levels ◽  
Baseline Fitness ◽  
Clinical Trial Information

4006 Background: Many pts with aGOAC are elderly and/or frail. We previously compared epirubin/ oxaliplatin/ capecitabine (EOCap) vs OCap vs Cap in a pick-the-winner study and found OCap best. GO2 was designed to find the optimum dose of OCap and to explore the use of an objective baseline geriatric assessment to individualize doses for maximum Overall Treatment Utility (OTU), a composite of clinical benefit, tolerability, QL and patient value. Methods: Pts with aGOAC were eligible if unsuitable for full-dose EOCap due to age or frailty, but fit for OCap; GFR ≥ 30, bili <2x ULN. Baseline assessment included global QL; symptoms; functional scales; comorbidity; frailty. Randomization was 1:1:1 to dose Level A (Ox 130 mg/m2d1, Cap 625 mg/m2bd d1-21, q21d), B (80% Level A doses) or C (60% Level A doses). Pts with GFR 30-50 ml/min or bili 1.5-2.0 xULN received 75% of the allocated dose of Cap. At 9 wks, pts were scored for OTU. Continuation thereafter was based on clinical judgement. Non-inferiority (vs A) was assessed using PFS censored at 12 months, with boundary HR 1.34 (based on discussion with pts and clinicians), needing 284 PFS events per 2-way comparison. Baseline fitness was assessed as predictive of OTU, overall and by interaction with dose level. Results: 514 pts were randomised, 2014-17, at 61 UK centres. Clinical trial information: 44687907. Non-inferiority of PFS is confirmed for Level B vs A (HR 1.09, CI 0.89-1.32) and for Level C vs A (HR 1.10, CI 0.90-1.33). Level C pts had less toxicity and better OTU outcomes than A or B. When analysed by baseline age, frailty and PS, Level C produced the best OTU even in younger, less frail and better PS patients; no group was identified who benefit more from the higher dose levels. Conclusions: This is the largest RCT to date specifically investigating frail and/or elderly aGOAC pts, and should guide future treatment. The lowest dose tested was non-inferior in terms of PFS and produced less toxicity and better overall treatment utility.[Table: see text]

Best supportive care (BSC) with or without low-dose chemotherapy (chemo) in frail elderly patients with advanced gastroesophageal cancer (aGOAC): The uncertain randomization of the GO2 phase III trial.

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. 4051-4051 ◽  
Author(s):  
Daniel Swinson ◽  
Mohan Hingorani ◽  
Zuzana Stokes ◽  
Jo Dent ◽  
Kamalnayan Guptal ◽  
...  
Keyword(s):  
Low Dose ◽  
Statistical Significance ◽  
Best Supportive Care ◽  
Phase Iii ◽  
Phase Iii Trial ◽  
Baseline Factors ◽  
Modern Context ◽  
Low Dose Chemotherapy ◽  
Baseline Health ◽  
Clinical Trial Information

4051 Background: Before 2000, trials comparing BSC +/- chemo for aGOAC showed overall survival (OS) benefit, but in predominantly fit patients (pts). We have revisited this question in a modern context, using low-dose chemo in a frail population, with comprehensive baseline health and frailty assessment. Methods: In the GO2 trial, elderly and/or frail aGOAC pts with a “certain” indication for chemo were randomised between 3 chemo doses. In this GO2 substudy, pts with an “uncertain” indication for chemo were instead randomised to BSC ± the lowest dose chemo. Pts were eligible if clinician and pt agreed the indication for chemo was uncertain. There was no PS threshold, but eGFR ≥30 and bili < 2xULN were required. Baseline assessment included global QL, symptom & functional scales, frailty and comorbidity. Randomisation was 1:1 to BSC alone, or with oxaliplatin 78 mg/m2 d1, capecitabine 375 mg/m2 bd d1-21 (modified if eGFR 30-50 ml/min or bili 1.5-2.0 xULN), q21d. QL was reassessed after 9 and 18 wks. The primary endpoint analysis was OS, adjusted for baseline factors. The sample size for this exploratory sub-study was not pre-set, but around 60 pts were anticipated. Results: 558 pts entered GO2 at 61 centres 2014-17, of whom only 45 pts (8%) at 21 centres entered this uncertain randomisation. This would provide 80% power at p = 0.05 (2-tailed) to detect an OS HR of 0.3. OS was shorter in pts with worse baseline PS (p<0.01) or distant mets (p<0.05). OS was not significantly improved with chemo; however we cannot exclude HR >0.32. QL deteriorated less with BSC+chemo than with BSC alone. Conclusions: In this frail, poor PS population, we observed a small survival benefit with chemo but this did not reach statistical significance. Clinicians should carefully consider BSC alone as a valid treatment option for aGOAC pts with poor PS and/or frailty. Clinical trial information: 44687907. [Table: see text]

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