Chemotherapy In Elderly Patients Research Articles

Treatment outcomes of proton beam therapy combined with retrograde intra-arterial infusion chemotherapy for locally advanced oral cancer in the elderly

The aim of this study was to evaluate the therapeutic efficacy and safety of proton beam therapy combined with retrograde intra-arterial infusion chemotherapy in elderly patients with locally advanced oral cancer. Between February 2009 and October 2019, 42 oral cancer patients aged ≥75 years were treated with this therapy. Median age was 80 years (range 75–90 years) and the median follow-up duration was 39 months (range 2–106 months). Of the 42 patients, 34 (81%) were diagnosed with stage IV cancer. The 3-year overall survival, local control, progression-free survival, and disease-specific survival rates were 56%, 69%, 32%, and 67%, respectively. Regarding acute toxicities, grade 3 neutropenia was observed in six patients (14%), anaemia in five (12%), acute kidney injury in one (2%), and oral mucositis in 18 (42%). Late toxicities of grade 3 were observed in seven patients: dysphagia in six (14%) and osteonecrosis of the jaw in one (2%). This study showed that proton beam therapy combined with retrograde intra-arterial infusion chemotherapy was effective for elderly patients with oral cancer, and toxicities were tolerable and manageable. The study findings suggest that this therapy is a potential treatment option for elderly oral cancer patients with difficulty in surgery and systemic chemotherapy.

Evaluation of the Efficacy and Safety of Chemotherapy in Elderly Patients with Multiple Myeloma under Different Frailty Scores

To compare the efficacy and safety of different chemotherapy regimens in elderly multiple myeloma (MM) patients with different Frailty scores. The clinical data of elderly patients with MM were retrospectively analyzed, including age, treatment regimen, efficacy, adverse reactions, and the Frailty score included in the activity of daily living score, the instrumental activity of daily living scale and the Charlson comorbidity index. The patients were divided into fit group, mediate fit group and frail group according to the scoring standard. The treatment efficiency and adverse reaction rates of elderly MM with different physical conditions treated by different chemotherapy regimens were analyzed. Among the 70 patients, the effective rates of the patients in fit group, the mediate fit group, and the frail group were 79.5%, 81%, and 40%, and the effective rates of the fit patients in double and triple groups were 54.5% and 89.3%, 70% and 90.9% for mediate fit patients, 42.9% and 33.3% for frail patients, the triple regimen in fit patients showed obvious advantages, and the difference showed statistically significant (P<0.05), while the efficacy for mediate patients and frail patients showed no significant difference. During the induction of bortezomib, the incidence of adverse reactions for the patients in the triple group (78.6%) was higher than 67.9% in the double group, and the difference showed no statistically significant (P>0.05).There was no significant difference in the 1-year overall survival rate of the patients and with molecular genetic abnormalities among each groups. The therapeutic effect is related to the patient's physical condition. For patients with healthy physique, the triple regimen should be used first. For patients with weak physical constitution, the chemotherapy regimen with low drug toxicity should be selected for safety.

Efficacy of prophylactic pegfilgrastim on day three of preoperative DCF chemotherapy in elderly patients with resectable esophageal cancer.

305 Background: Preoperative neoadjuvant chemotherapy with cisplatin plus 5-FU (CF) is the standard treatment for resectable esophageal cancer (EC). Docetaxel plus CF (DCF) is also a promising preoperative treatment; however, a high frequency (5%-30%) of febrile neutropenia (FN) has been reported in patients (pts) receiving DCF, and elderly pts reportedly have a high risk of FN. The use of primary prophylactic pegfilgrastim (PG) on day 3 of DCF in resectable EC pts might prevent FN. We conducted a retrospective review to assess the efficacy of primary prophylactic PG administration on day 3 of preoperative DCF in elderly pts with resectable EC. Methods: EC pts who had received preoperative DCF between 2009 and 2021, were ≥70 years old, and had adequate organ functions and an adequate PS were eligible for this retrospective study. Pts were assigned to receive either PG-containing DCF (day3 prophylactic PG: D3PG) or standard DCF (non-prophylactic PG: NPG). Three courses of DCF (DTX [day 1]: 70 mg/m2, CDDP [day 1]: 70 mg/m2, 5-FU [continuous infusion on days 1-5]: 750 mg/m2, every 3 weeks) were planned, and antibiotic prophylaxis was mandatory on days 5-15 in each group. In the D3PG group, PG was administered subcutaneously on day 3. We retrospectively evaluated the relative dose intensity (RDI), histopathological efficacy, and adverse events (CTCAE ver5.0). Results: A total of 52 pts (D3PG, 17; NPG, 35) with a median age of 72 years were identified. The PS (0/1/2) and clinical stage (I/II/III/IVB [only supraclavicular lymph node]) were 10 (58.8%)/5 (29.1%)/2 (11.8%) and 0/1 (5.9%)/10 (58.8%)/6 (35.4%) in the D3PG group and 20 (57.1%)/15 (42.9%)/0 and 2 (5.7%)/5 (14.3%)/24 (68.6%)/4 (11.4%) in the NPG group, respectively. Three pts discontinued treatment because of toxicity (FN and nausea in D3PG and FN and diarrhea in NPG) and progression in each group, and all the pts underwent surgery. The RDIs (DTX/CDDP/5-FU) were 0.870/0.862/0.871 in the D3PG group and 0.833/0.829/0.830 in the NPG group. Five (29.4%) pts in the D3PG group and 10 (28.6%) in the NPG achieved a pCR. The common grade ≥3 adverse events (D3PG/NPG) were leukopenia (17.6%/51.4%), neutropenia (11.8%/71.4%) and FN (5.9%/20.0%). Conclusions: The use of primary prophylactic PG on day 3 of preoperative DCF improved the treatment safety treatment in elderly pts with resectable EC. No significant differences in treatment efficacy were seen between the D3PG and NPG groups despite the higher number of pts with a worse general condition or more advanced disease in the D3PG group than in the NPG group.

Benefit for single-agent adjuvant chemotherapy in elderly patients with locally advanced gastric adenocarcinoma

Current NCCN guidelines exclude the possibility of using single-agent adjuvant chemotherapy in locally advanced gastric adenocarcinoma, while allowing doublet chemotherapy. However, single-agent adjuvant chemotherapy is a valid treatment option in other gastrointestinal malignancies, preferred for elderly and/or frail patients. The current study used a nationwide oncology database to assess the benefit of single-agent adjuvant chemotherapy, specifically in the elderly population. Using the National Cancer Database (2004-2016) we identified 1953 individuals with non-metastatic gastric adenocarcinoma who underwent upfront D2 gastrectomy with pathologic stage ≥ T3 or Npos and free surgical margins, and had not received either preoperative chemotherapy or pre-/postoperative radiotherapy. We used IPTW analysis to compare overall survival between individuals receiving either single- or multi-agent adjuvant chemotherapy, or referred to observation alone. Individuals receiving single-agent chemotherapy had an overall survival benefit compared with observation alone, with an HR of 0.70 (95% CI 0.55-0.88, p < 0.001). Individuals over the age of 65 had an OS benefit with an HR of 0.61 (95% CI 0.46-0.82, p < 0.001). Comparing individuals over the age of 65 receiving single- vs. multi-agent chemotherapy, there was no overall survival difference with an HR of 0.87 (95% CI 0.64-1.18, p = 0.38). Single-agent adjuvant chemotherapy with a fluoropyrimidine in locally advanced gastric adenocarcinoma following D2 gastrectomy can improve overall survival in elderly patients. Clinicians may consider using either capecitabine or 5-FU as a treatment option in the adjuvant setting for this age group.

The clinical outcomes of combination chemotherapy in elderly patients with advanced biliary tract cancer: an exploratory analysis of JCOG1113

In the FUGA-BT trial (JCOG1113), gemcitabine plus S-1 (GS) showed non-inferiority to gemcitabine plus cisplatin (GC) in overall survival (OS) with good tolerance for patients with advanced biliary tract cancer (BTC). We performed a subgroup analysis focused on the elderly cohort of this trial. All 354 enrolled patients in JCOG1113 were classify into two groups; < 75 (non-elderly) and ≥ 75 years (elderly) group. We investigated the influence of age on the safety analysis, including the incidence of chemotherapeutic adverse events and the efficacy analysis, including OS. There were no remarkable differences in OS between the elderly (n = 60) and the non-elderly groups (n = 294). In the elderly group, median OS was 12.7 and 17.7 months for those who received GC (n = 20) and GS (n = 40), respectively. The prevalence of all-grade adverse events was similar between the elderly and the non-elderly groups. However, among the elderly group, Grade ≥ 3 hematological adverse events were more frequently observed in the GC arm than in the GS arm. The clinical outcomes of combination chemotherapy in elderly patients with advanced BTC were comparable to non-elderly patients. GS may be the more favorable treatment for elderly patients with advanced BTC.

Cisplatin Neoadjuvant Chemotherapy in an Aging Population With Muscle-Invasive Bladder Cancer.

Jun Gong, MD, gives his perspective on neoadjuvant chemotherapy in elderly patients with muscle-invasive bladder cancer.

Use of Neoadjuvant Chemotherapy in Elderly Patients With Muscle-Invasive Bladder Cancer: A Population-Based Study, 2006-2017.

Objectives/Introduction Neoadjuvant chemotherapy (NAC) prior to radical cystectomy (RC) for muscle-invasive bladder cancer (MIBC) is associated with survival benefit across patients of all ages, yet it is not offered to many elderly patients. We aimed to evaluate age-based disparity in treatment and outcomes of MIBC. Methods Using the National Cancer Database, we identified patients with MIBC from 2006 to 2017. Use of treatment modalities was compared between age groups. A second analysis compared perioperative outcomes and overall survival (OS) in elderly patients (70 years or older) undergoing RC with NAC vs no NAC. Propensity score weighting (PSW) was used for each analysis. Results In 70,911 patients, use of NAC with RC was lower in patients 70 years or older (7.2% vs 20.9%; P < .001). In patients 70 years or older undergoing RC, NAC was associated with shorter inpatient stay (8.5 vs 9.6 days; P < .001), decreased 30-day readmission (8.6% vs 10.6%; P <.001), and lower 30- and 90-day mortality (1.5% vs 3.1%; P = .01; and 4.9% vs 7.7%; P = .003, respectively). On weighted multivariate regressions, NAC predicted shorter length of stay and lower 30-and 90-day mortality. Elderly patients receiving NAC had improved OS compared with RC alone (P = .0011, 2010-2013; P < .001, 2014-2016). Conclusions Despite increased omission of NAC in patients 70 years or older, elderly patients receiving NAC and RC had improved perioperative outcomes and OS compared with those undergoing RC alone. There may be selection bias unaccounted for with our PSW; however, our results provide compelling evidence that NAC does not compromise surgical outcomes in appropriately selected elderly patients. Patients of advanced age who are candidates for RC should be offered NAC.

Serum Albumin Levels Strongly Predict Survival Outcome of Elderly Patients with Diffuse Large B-Cell Lymphoma Treated with Rituximab-Combined Chemotherapy.

Background: In the current Japanese aging society, a high number of very elderly patients (age ranged from 80 to 93) with diffuse large B-cell lymphoma (DLBCL, most frequent hematological malignancy), who require chemotherapy are encountered. However, standard chemotherapy can result in severe adverse effects in elderly patients. Although various scoring systems are available to assess frailty, they are too complicated to immediately make a therapeutic decision, and studies on indications for chemotherapy in elderly patients are few. Materials and Methods: In the present study, we retrospectively analyzed the clinical records of 56 patients with DLBCL aged 80 or older who received R-CHOP or similar chemotherapy. Association of various clinical parameters, including performance status, stage, B symptom(s), laboratory data and relative dose intensity and survival outcomes was examined. Results: Pretreatment serum albumin level was identified as the only factor that predicts overall and progression-free survivals. Conclusion: We have concluded that very elderly DLBCL patients aged 80 or older with hypoalbuminemia may be unfit for standard chemotherapy, regardless of other factors. Alternative or palliative therapy should be considered for those patients.

Efficacy Evaluation of Azacytidine Combined with Chemotherapy in Elderly Patients with Acute Myeloid Leukemia

Efficacy Evaluation of Azacytidine Combined with Chemotherapy in Elderly Patients with Acute Myeloid Leukemia

1374P A randomized phase III study to compare efficacy and safety between combination therapy and monotherapy as first-line chemotherapy in elderly patients with advanced gastric cancer (KCSG ST13-10)

1374P A randomized phase III study to compare efficacy and safety between combination therapy and monotherapy as first-line chemotherapy in elderly patients with advanced gastric cancer (KCSG ST13-10)

Survival and complications of cytoreductive surgery and hyperthermic intraperitoneal chemotherapy in elderly patients: a systematic review and meta-analysis.

Peritoneal cancer is an uncommon form of terminal malignancy with substantial morbidity and mortality. While both young and elderly population groups with peritoneal cancer are treated by joint cytoreductive surgery and hyperthermic intraperitoneal chemotherapy, studies suggest that they might have a differential prognostic outcome in terms of postoperative morbidity and mortality. To date, only one review has attempted to evaluate the comparative impact of postoperative complications and overall mortality in these age groups. However, a recent publication of several high-quality cohort trials needs an update of the existing consensus. To compare the impact of cytoreductive surgery and hyperthermic intraperitoneal chemotherapy on postoperative complications and overall mortality in younger and elderly population groups. A systematic search of the academic literature was performed according to the PRISMA guidelines across five databases: Web of Science, EMBASE, CENTRAL, Scopus, and MEDLINE. A random-effect meta-analysis was conducted to evaluate the comparative outcomes between the impact of cytoreductive surgery and hyperthermic intraperitoneal chemotherapy on postoperative complications and overall mortality in younger and elderly population groups. From 963 studies, 16 eligible studies that evaluated the comparative outcomes of morbidity and mortality between 3067 young and 878 elderly patients undergoing cytoreductive surgery and hyperthermic intraperitoneal chemotherapy were included. A meta-analysis revealed higher risks of postoperative complications (Odds ratio: 1.18, 95% C.I: 0.90 to 1.55) and overall mortality (3.28, 1.93 to 5.5) for elderly patients as compared to the younger patients undergoing cytoreductive surgery and hyperthermic intraperitoneal chemotherapy. There were no differences in risks of the onset of anastomotic leakage (1.0, 0.47 to 2.14) and duration of hospital stay (Hedge's g: 0.02, -0.08 to 0.14) between elderly and younger patients undergoing cytoreductive surgery and hyperthermic intraperitoneal chemotherapy. The study provides updated evidence regarding poor postoperative morbidity and mortality outcomes in elderly patients as compared to younger patients undergoing cytoreductive surgery and hyperthermic intraperitoneal chemotherapy and may help clinicians to better stratify the risks associated with the conventional management of peritoneal carcinomatosis in elderly population groups.

Clinical impact of pembrolizumab combined with chemotherapy in elderly patients with advanced non-small-cell lung cancer

ObjectivesCombination therapy of immune checkpoint inhibitors and chemotherapy is considered to be one of the standard treatment options for patients with advanced non-small-cell lung cancer (NSCLC). However, the clinical significance of immune checkpoint inhibitors combined with chemotherapy in elderly patients with NSCLC has not yet been fully understood. Therefore, this study aimed to evaluate how aging affects the therapeutic impact of chemotherapy combine with immune checkpoint inhibitors in elderly patients. Materials and methodsWe retrospectively analyzed 203 patients with advanced NSCLC who were treated with the combination therapy of pembrolizumab and chemotherapy between January 2019 and December 2019 at 12 institutions in Japan. We analyzed the clinical impacts of age on the following two groups: those who received pembrolizumab with platinum and pemetrexed (pemetrexed regimen) and those who received pembrolizumab with carboplatin and nab-paclitaxel/paclitaxel (paclitaxel regimen). Progression-free and overall survival were assessed via the Kaplan-Meier method. ResultsMultivariate analysis demonstrated that progression-free and overall survival were significantly shorter in elderly patients (aged ≥75 years) with NSCLC than in non-elderly patients (aged <75 years) with NSCLC in the pemetrexed regimen group. In contrast, there were no significant differences in progression-free and overall survival between elderly patients and non-elderly patients with NSCLC in the paclitaxel regimen group. In elderly patients with NSCLC, a programmed death-ligand 1 tumor proportion score of ≥50% was significantly associated with progression-free survival, and performance status of ≥2 was significantly associated with overall survival. Low albumin level (<3.5 g/dL) was significantly associated with both progression-free and overall survival. ConclusionThe results of this retrospective study show that the pemetrexed regimen, but not the paclitaxel regimen, was related to poor clinical outcomes in elderly patients with NSCLC.

Reviewing the Outcomes of Different Treatment Approaches in Elderly Pancreatic Cancer Patients.

The incidence of pancreatic cancer is age dependent. Ninety percent of new diagnoses occur in patients older than 55 years. Despite the association with age and cancer, elderly patients are historically underrepresented in clinical trials. Thus, optimal management of elderly patients has a lack of data. The purpose of this retrospective study was to investigate the outcomes of palliative chemotherapy in elderly patients with pancreatic cancer compared with supportive care alone. Unicentric data were reviewed on all elderly patients (defined as age >65 years) with a diagnosis of pancreatic cancer from 2008 through 2019 to compare outcomes in those who received chemotherapy versus supportive care alone. The study reviewed 665 patients with a median age of 75 years (mean, 75.7 years) and average Charlson Comorbidity Score of 5.74. Of them, 291 received chemotherapy and 363 received supportive care only. Chemotherapy was associated with a median overall survival of 250 versus 93 days with supportive care (P < 0.0001). Analysis showed improved survival for all age ranges, cancer stages, and Charlson Comorbidity Scores. Elderly pancreatic cancer patients can benefit from palliative chemotherapy, and it should be considered, especially in patients with fewer medical comorbidities and better functional status.

Cisplatin-Based Neoadjuvant Chemotherapy for Elderly Patients with Muscle-Invasive Bladder Cancer: Is It Feasible?

Cisplatin-based neoadjuvant chemotherapy (C-NAC) has been the standard of care in localized muscle-invasive bladder cancer (MIBC). However, the feasibility and benefit of C-NAC in elderly patients remain uncertain since this population has always been underrepresented in pivotal trials and is often barred from chemotherapy in routine practice because of their perceived frailty. Therefore, in order to evaluate the effectiveness of C-NAC in elderly patients with MIBS, we retrospectively reviewed the medical files of patients (cT2-4, N0-3, and M0) treated at our institution and aged 75 or older at the time of the first chemotherapy cycle. From May 2012 to March 2020, 51 patients aged 75 to 90 received C-NAC. Among them, 38 patients received methotrexate, vinblastine, doxorubicin, and cisplatin (MVAC) and 13 patients received gemcitabine and cisplatin (GC). In this study, the primary endpoint was the feasibility of C-NAC, evaluated as the percentage of patients who underwent at least four chemotherapy cycles. Overall feasibility of a complete four-cycle chemotherapy course was 75% (dose-dense MVAC [dd-MVAC]: 76%; GC: 69%). Incidence of grade 3-4 adverse events was 57%, mostly driven by hematological toxicity from dd-MVAC, and the incidence of febrile neutropenia was 6%. These results indicate the feasibility of C-NAC in elderly patients without any contraindication to cisplatin. A coordinated multidisciplinary approach, including a geriatric oncologist, may help to identify patients at increased risk for chemotherapy-induced toxicity, especially in patients aged 85 or older.

Changes in the quality of life score following preoperative chemotherapy in elderly patients with esophageal cancer.

Various functions in elderly patients with esophageal cancer deteriorate easily and their quality of life can be adversely affected by treatment. The age groups covered in previous studies are wide, and the impact on the elderly individuals is unknown. This study examined changes in quality of life scores after preoperative chemotherapy to clarify aspects of physical, psychological, and social quality of life in elderly patients with esophageal cancer. Thirty-six patients aged over 65years, who were scheduled to undergo preoperative chemotherapy for esophageal cancer surgery, were enrolled. The survey questionnaire comprised the EORTC QLQ-C30 Japanese Language Version, EORTC QLQ-OES 18 Japanese Language Version, and G8. The surveys were conducted before chemotherapy (pre-CT) and after chemotherapy (post-CT). In the functional scale of QLQ-C 30, physical functioning decreased significantly, while emotional functioning increased significantly post-CT (p = 0.021, p = 0.030, respectively). Global health status was not changed. In QLQ-OES18, the mean symptom scale score decreased significantly for dysphagia, trouble swallowing saliva, choking, eating, reflux, and pain post-CT (p = 0.014, p = 0.034, p = 0.033, p = 0.022, p = 0.026, p = 0.016, respectively). The mean G8 score decreased significantly from 11.7 to 10.7 (p = 0.022) post-CT, but the proportion of patients with dysfunction decreased. Quality of life scores of elderly patients with esophageal cancer who received preoperative chemotherapy decreased in terms of physical function but improved in terms of esophageal cancer symptoms and mental function. Our results suggest that alleviation of symptoms contributed to the improvements in mental health.

Effect of Adjuvant Chemotherapy on Survival of Elderly Patients With Stage III Colorectal Cancer.

The aim of this study was to investigate the efficacy and safety of adjuvant chemotherapy in elderly patients with stage III colorectal cancer in a real-world setting. A total of 165 patients of ≥70 years of age with stage III colorectal cancer who underwent a curative operation between 2008 and 2020 were enrolled in this study. Among septuagenarians, the relapse-free and overall survival rates in the single-agent therapy group and the combination therapy group were significantly better than those in the group treated by surgery alone. However, no significant differences were observed in the relapse-free and overall survival rates of the single-agent therapy group and the combination therapy group. Among octogenarians in whom all regimens were single-agent therapy, adjuvant chemotherapy tended to improve the relapse-free and overall survival rates but not the time to recurrence or cancer-specific survival. Single-agent adjuvant chemotherapy may be a useful treatment option for septuagenarians with stage III colorectal cancer. However, the efficacy of adjuvant chemotherapy in octogenarians was not shown in this study.

P-74 The impact of first-line chemotherapy in elderly patients with advanced pancreatic cancer: A mono-institutional retrospective study

Pancreatic cancer median age at diagnosis is 70 years old. However, elderly patients (pts) are underrepresented in randomized clinical trials (RCTs) and chemotherapy efficacy and safety data in this population are limited. Herein, we present a retrospective analysis of an elderly population treated at our institution, investigating the role of baseline clinical factors in guiding treatment decision-making. Pts aged ≥70 years old receiving first-line chemotherapy for advanced pancreatic cancer (APC) were included in the analysis. The primary end-points were progression-free survival (PFS) and overall survival (OS). The following variables were collected: gender; age (≥ 70 and < 75 years vs ≥ 75 years); baseline ECOG PS (0-1 vs 2-3); site of primary tumor (head/uncinate process vs body/tail); disease stage (locally advanced vs metastatic); baseline CA 19.9 (< vs ≥ 200); chemotherapy regimen; comorbidities (yes vs no); number of comorbidities (0-1 vs ≥ 2). Univariate and multivariate analysis for PFS and OS were performed. A total of 169 APC pts aged ≥70 years old, receiving first-line chemotherapy between March 2015 and August 2020, were included in the analysis. The median age was 76 years (70-89), ECOG PS was 0-1 in 77% of pts; 70% were metastatic; 70% of pts had a head/uncinate process primary tumor; 25% had baseline CA 19.9 ≥ 200; 9.4% of pts had no comorbidities and 50% had ≥2 comorbidities. The majority of pts received gemcitabine nab-paclitaxel (60%), other regimes included gemcitabine (28%), FOLFIRINOX (5%), capecitabine (4%), FOLFOX (2%) and FOLFIRI (1%). The overall population median PFS and OS were 6.5 (median follow-up 19.1 months) and 11 months (median follow-up 21.8 months), respectively. Out of 164 pts evaluable, 38 (23%) pts achieved a partial response and 58 (35%) a stable disease, with a disease control rate of 58%. At the multivariate analysis, ECOG PS 0-1 was independently associated with both improved PFS (p=0.005) and OS (p=0.0084). At the multivariate analysis for PFS, locally advanced stage was also significantly associated with better PFS (p=0.036). In pts with ECOG PS 0-1 vs 3-4 the median PFS was 6.7 vs 3.3 months (p=0.0004) and median OS was 11.3 vs 5.5 moths (p=0.003), respectively. Despite the retrospective nature of the analysis and the limited sample size, we observed that elderly APC pts can benefit from first-line treatment, achieving survival outcomes comparable to the ones reported for younger pts in RCTs. On the basis of our results, the baseline ECOG PS can be considered a prognostic factor for both PFS and OS. In conclusion, elderly pts should not be precluded from active treatment, and careful patient selection, mainly according to baseline ECOG PS, should guide treatment indication.

P-272 Significance of adding oxaliplatin to postoperative adjuvant chemotherapy in elderly patients with colorectal cancer

The benefit of postoperative adjuvant chemotherapy with oxaliplatin (OX) for elderly patients with colorectal cancer (CRC) remains controversial. In meta-analyses of previous clinical trials, the benefit of adding OX to fluoropyrimidine (Fp) was not observed in elderly patients aged over 70 years because they died due to causes other than CRC. However, these clinical trials did not include Japanese patients. The aim of this study was to confirm the benefit of adding OX to Fp in the adjuvant setting for Japanese elderly patients with CRC because Japan is one of the countries with the highest average life expectancy (84.3 years according to WHO data in 2019).

A Prospective, Non-Randomized, Multicenter, Phase II Study to Assess Safety and Efficacy of the Infusion of Peripheral Blood Stem Cells Obtained from HLA-Haploidentical Familial Donors (mHaploSCI) after Standard Chemotherapy in Elderly Patients with Acute Myeloid Leukemia at Intermediate or Adverse Risk

A Prospective, Non-Randomized, Multicenter, Phase II Study to Assess Safety and Efficacy of the Infusion of Peripheral Blood Stem Cells Obtained from HLA-Haploidentical Familial Donors (mHaploSCI) after Standard Chemotherapy in Elderly Patients with Acute Myeloid Leukemia at Intermediate or Adverse Risk

Hypomethylating Agents Versus Intensive Chemotherapy in Elderly Patients (Age ≥ 70) with Acute Myeloid Leukemia with High White Blood Cell Count

▪BackgroundAcute myeloid leukemia (AML) is primarily a disease of older adults, with 40-50% of patients ≥ 70 years old at diagnosis. Optimal frontline therapy for elderly AML patients remains controversial. Intensive chemotherapy (IC) is often favored in those AML patients who present with leukocytosis (P-AML), yet the evidence to support this practice as opposed to lower intensity therapy is scarce. We aimed to investigate the outcomes of older patients with P-AML based on treatment choice of intensive chemotherapy (IC) vs hypomethylating agents (HMA).MethodsWe retrospectively analyzed 983 elderly AML patients (age ≥ 70 years) treated at Moffitt Cancer Center between 1995 and 2016. Patients with prior exposure to HMA for non-AML diagnoses were excluded. We focused on P-AML patients, defined as baseline WBC ≥ 10x109/L, who received initial therapy with either: intensive chemotherapy (IC) (defined as daunorubicin/cytarabine or equivalent) or hypomethylating agents (HMA) (azacitidine (AZA) or decitabine (DEC)). Age, type of AML, history of antecedent hematologic disease, cytogenetics (per European LeukemiaNet (ELN) criteria), Eastern Cooperative Oncology Group (ECOG) performance status, Charlson comorbidity Index (CCI), complete blood counts and myeloblast percentage at time of diagnosis were obtained for each patient. Kaplan-Meier analysis was performed to calculate overall survival (OS) and the log-rank test was used to determine significance where a p-value of 0.05 was defined as significant. Fisher's exact t-test, hazard ratios (HR) and confidence interval (CI) were calculated using GraphPad Prism v7.03. Univariate and multivariate analysis for the baseline characteristics and type of therapy were performed using SPSS v24.0 to determine prognostic impact.ResultsWithin the entire cohort of older AML patients, we identified 156 who were treated with either HMA (n=41) or IC (n=115). Baseline characteristics of these patients are described in Figure 1A. Significant baseline differences in age, hemoglobin, WBC, ELN cytogenetic category, marrow blast %, and CCI score were observed between the HMA and IC groups. Most notably, the HMA group were older (median age 77 yrs vs 74 yrs, p=0.0037), had a higher incidence of poor-risk cytogenetics (36.6% vs 7%), and were more likely to have CCI score ≥ 3 (29.3% vs 8.7%).Median time of initial treatment was 4.3 months (range: 0.10-70.0 months) in the HMA group compared to 0.5 months (range: 0.33-1.90months) in the IC group. Median OS of the entire group was 7.85 mo. Median OS in the HMA-treated patients was superior to IC treated patients (13.7 mo vs. 5.1 mo, HR 0.63, 95% CI 0.443 - 0.886, p=0.0082) (Figure 1B). The 12 month survival rate was 55.0% in the HMA group and 31.0% in the IC group (p=0.0082). Fifty-two (33%) patients achieved CR/CRi. There was no difference in CR/CRi rates between HMA or IC treated cohorts (30.0% vs. 34.8%, p=0.6983). Rate of relapse upon achievement of CR/CRi was not statistically significant between HMA and IC cohort (41.7% vs. 62.5%, p=0.3181). The 30-day mortality rate was lower in the HMA group compared to the IC group (7.3% vs 24.4%, p=0.0217).Univariate analysis identified treatment type (p<0.0001), cytogenetic risk category (p <0.0001), and ECOG performance status (p<0.0001) as significant prognostic factors for OS. Multivariate analysis identified IC treatment (HR 2.01, 95% CI 1.24-3.26, p=0.005) and poor ECOG performance status (HR 4.30, 95% CI 1.182-15.659, p=0.027) as independent negative predictors of OS.ConclusionsElderly patients (age ≥ 70) with proliferative AML appear to achieve a survival advantage with HMA-based frontline therapy compared to IC, despite a disproportionately higher incidence of traditionally adverse prognostic features (poor-risk cytogenetics, high CCI score) in the HMA group. The reasons for this observation are unclear, but could relate to a higher early death rate with IC or biologic/molecular features that induce greater sensitivity to HMAs, which should be studied in future analyses. Although this study was limited by small size and retrospective nature, our findings cast doubt on the notion that intensive therapy should be the standard frontline approach in elderly patients proliferative/high WBC AML. [Display omitted] DisclosuresSallman:Celgene: Research Funding. Padron:Incyte: Honoraria, Research Funding. Komrokji:Novartis: Honoraria, Speakers Bureau; Celgene: Honoraria. Lancet:Biopath, Biosight, Boehringer Ingelheim, Celator/Jazz, Celgene, Janssen, Karyopharm Therapeutics, and Novartis: Consultancy; Pfizer: Other: Institutional research funding.