Patients In Standard-dose Group Research Articles

Efficacy of Low Dose Generic Antithymocyte Globulin and Cyclosporine in Idiopathic Aplastic Anemia

Background: In transplant ineligible idiopathic aplastic anemia (IAA) patients, immunosuppressant therapy (IST) with equine Anti-thymocyte globulin (eATG) and cyclosporine is a standard treatment option. In resource constraint settings, where cost is an indisputable determinant of care, haematologists perennially face challenges to come forward with economical yet effective treatment strategies to ensure wider affordability. To explore cost-effective therapeutic options for this under addressed patient population, we studied the efficacy of a lower dose of generic eATG.Methods: Transplant ineligible AA patients (age > 12 years) treated with generic eATG (Thymogam) and cyclosporine from January 2010 to December 2016 were retrospectively analysed. Efficacy of low dose generic eATG (25 mg/kg/d for 4 days) was analysed and compared with standard dose of generic eATG (40 mg/kg/d for 4 days). The choice of eATG dose was based on affordability of the patient. The patients who had completed eATG therapy and followed up at 3 months and 6 months were included in efficacy analysis. Overall response rate (ORR) [including complete response (CR) and partial response (PR)] at 3 months and 6 months were analysed.Results: Thirty-four AA patients treated with generic eATG and cyclosporine were analysed. Mean age was 23.74 years (range 13-45 years); 22 (64.7%) were males. PNH clone was present in 13 (38.2%) patients. Median duration of follow up was 21.1 months (range 3-42 months). Out of 34 patients included in the study, one patient died on day 15 of therapy due to febrile neutropenia, 32 followed up at 3 months and 30 completed 6 months follow up. ORR in the study population was 48.8% at 3 months and 60.6% at 6 months. Difference between ORR at 3 months with low dose (42.9%, CR 0, PR 6) and standard dose eATG (47.3%, CR 0, PR 9) was not significantly significant (p = 0.8). Similarly, difference in ORR at 6 months was not statistically significant between low dose (53.8%, CR 0, PR 7) and standard dose (61.1%, CR 1, PR 10) eATG (p = 0.537). Serious adverse events were observed in three patients in low dose group [non-fatal febrile neutropenia 1; seizure 1; acute kidney injury (AKI) 1] and 7 patients in standard dose group [death due to febrile neutropenia 1; non-fatal febrile neutropenia 2; intracranial bleed 1; AKI 2; flash pulmonary edema 1]. On multivariate analysis for ORR at 6 months, none of the expected variables (age, absolute neutrophil count, absolute lymphocyte count, interval between onset of symptoms to initiation of therapy) could reach statistical significance. Two patients relapsed (after 30 months and 36 months, respectively) after receiving low dose ATG and three patients relapsed after receiving standard dose ATG (after 18 months, 26 months and 38 months, respectively).Conclusion: We found that efficacy of low dose generic eATG was similar to the standard dose generic eATG. We conclude that IST with low dose generic eATG and cyclosporine is an efficacious and economical approach that can potentially enhance treatment affordability in IAA patients. However, prospective studies with larger number of patients are needed to further validate these results. DisclosuresNo relevant conflicts of interest to declare.

The dose-optimisation of lenvatinb for patients with unresectable hepatocellular carcinoma in clinical practice: A retrospective analysis of real-world evidence in China.

280 Background: Lenvatinib has become available as first-line therapy in patients with unresectable hepatocellular carcinoma (u-HCC). Although 8mg or 12mg/day is the standard starting dose according to weight, the high rate of adverse events (AEs) leading to dose reduction often limits its application. Various dosing schedules are used clinically to alleviate toxicities in practice. This study evaluated the safety and antitumor activity of two dosing strategies for lenvatinib administrations. Methods: Patients administered lenvatinib for u-HCC between April 2018 and July 2019 were enrolled. The dose-escalation strategy was conducted as follow, starting dose 4mg/day orally with biweekly escalation (As common AE always occurred within 2 weeks after administered), per 4 mg increment, to 8 or 12mg finally per body weight if no significant drug-related (no more than G2) adverse events occurred. Patients with a standard-dose strategy (8/12mg/day orally per body weight) were also included for comparison.Objective response rate(ORR) and progression-free survival (PFS) were assessed according to RECIST1.1 criteria. Dose-reduction rate was recorded and treatment-related adverse events (TRAE) was evaluated according to the CTCAE 5.0. Results: Totally 56 patients were included (37 in dose-escalation group and 19 in standard-dose group). The mean weight was 64.79±1.66 kg in dose-escalation group and 58.76±2.45 kg in standard-dose group, BCLC stage C proportion was 51.4% and 63.2%, Child-pugh B proportion was 16.2% and 5.3% respectively. Baseline demographic parameters were comparable between two groups (P>0.05). There was no significant difference in response rate (32.43% vs 42.1%, P=0.335), disease control rate (86.4% vs 84.2%, P=0.686) and PFS (P=0.631). The proportion of patients who reached the full dose (per weight) was also similar (48.6% vs 63.2%, p=0.399). Dose reduction rate was significantly higher in standard-dose group than dose-escalation group (36.8%vs 13.5%,p=0.044). Although, no difference in grade 3/4 adverse events was found between two groups (P=0.083), patients in standard-dose group(36.8%,7/19) have a higher incidence trend of G3/4 AEs than those of dose-escalation group(16.2%,6/37). Conclusions: The dose-escalation strategy may be an alternative approach to prolong lenvatinib treatment period, with comparable efficacy and more tolerance. More data are needed to confirm the long-term efficacy and safety of the dose-escalation strategy.

The efficacy and safety of high dose versus standard dose radiotherapy in concurrent chemoradiotherapy for patients with esophageal squamous cell carcinoma

Objective: To compare the efficacy and treatment-related toxicity of high dose versus standard dose radiotherapy in concurrent chemoradiotherapy (CCRT) for patients with esophageal squamous cell carcinoma (ESCC). Methods: From 2005 to 2012, 183 pairs of patients with esophageal squamous cell carcinoma in the Fourth Hospital of Hebei Medical University were enrolled, all had undergone CCRT based on three-dimensional conformal radiotherapy (3D-CRT) or intensity-modulated radiotherapy (IMRT). A propensity score was constructed to match the cohort. The overall survival (OS), local control (LC) probability, as well as the acute and late toxicities between standard-dose and high-dose groups were compared. Results: Patients in the high-dose group had significantly better OS and LC probability compared with those in the standard-dose group: the 3-, 5- and 10-year LC rate were 60.9%, 57.6%, 52.3% versus 50.8%, 46.4%, 30.8%, respectively (P=0.032). The 3-, 5- and 10-year OS were 44.3%, 36.9% and 24.5% for high-dose group, and 31.7%, 20.6% and 14.1% for the standard-dose group, respectively(P=0.002). The incidence of acute radiation esophagitis (especially in grade 2 and 3) was 63.9% in high-dose group, which was significantly higher than that in the standard-dose group (59.6%). Severe (≥ grade 3) late-onset esophagitis was observed in neither group. The grade 4 acute esophagitis was rare. There was no significant difference in the incidence of radiation pneumonitis, gastrointestinal reactions or hematological toxicities between the two groups. Six patients in high-dose group and two patients in standard-dose group experienced ≥ grade 4 leukocytopenia, while no one experienced > grade 3 thrombocytopenia and anemia in both group. Conclusions: 60 Gy was the preferred dosage of CCRT in patients with ESCC. Compared with standard-dose, the high-dose CCRT yielded slightly increased mild to moderate acute radiation esophagitis, while life-threatening toxicities were not increased.

Locoregional Recurrence of De-escalated Radiation Dose in Selected Nasopharyngeal Carcinoma: Experience from a Single Center Institution

In the era of intensity modulated radiotherapy (IMRT), nasopharyngeal carcinoma (NPC), especially in stage T1-3, could achieve excellent locoregional control rate higher than 90% after definitive radiotherapy. The outstanding locoregional controlling may lead to dose de-escalation in highly selected patients. In order to assess the locoregional recurrence and long-term outcome of de-escalated dose in T1-3 NPCs treated with IMRT, a retrospective propensity score analysis was conducted. A total of 264 patients diagnosed with T1-3NanyM0 nasopharyngeal carcinoma between June 2011 and June 2015 were retrospective analyzed. With a median age of 50 years old, 66 patients were female and 198 were male. All the patients were treated with IMRT. The prescription IMRT dose, namely the standard dose, in our institution is 69.96Gy/2.12Gy/33F or 70Gy/2Gy/35F to primary tumor and cervical metastatic lymph nodes, 60.06Gy/1.82Gy/33F or 59.5Gy/1.7Gy/35F to high risk target and 50.96Gy/1.82Gy/28F or 51Gy/1.7Gy/30F to low risk target. About 74% of these patients were treated with induction chemotherapy, 67% were treated with concurrent chemotherapy. With a median follow-up time of 48 months. The 5-year locoregional failure free survival (LRFS), distant metastasis free survival (DMFS), disease free survival (DFS), and overall survival (OS) were 90.0%, 81.2%, 76.1% and 83.5%, respectively. Thirty patients received IMRT dose less than prescription dose, categorized as dose de-escalation group, with a median dose of 64Gy (60-68Gy). Of the 30 patients in dose de-escalation group, 24 were treated with induction chemotherapy and 21 were treated with concurrent chemotherapy. Other 234 patients received exactly prescription dose were categorized as standard dose group, with irradiation dose of 70Gy. Propensity scores were computed (30 patients for dose de-escalation group and 60 patients in standard dose group), and there is no significant difference in 5-year LRFS and 5 year OS between two groups (90.1% and 82.5% in standard dose group; 92.0% and 80.1% in dose de-escalation group, p=0.354 for LRFS and 0.879 for OS). No independent prognostic factor, including age, gender, T stage, N stage and RT dose, was associated with loco-regional failure in multivariate analysis. In our results, highly selected T1-3 nasopharyngeal carcinoma, especially those with response to induction chemotherapy, a moderate de-escalation dose delivered with IMRT are with comparable outcomes to those of standard dose.

Abstract No. 536 Boosted superselective radioembolization may reduce local recurrence in hepatocellular carcinoma patients of BCLC A/B stage

To address the efficacy of boosted superselective radioembolization with glass microspheres for hepatocellular carcinoma of BCLC A/B stage. From March 2016 to April 2017, 28 patients with hepatocellular carcinoma (HCC) were treated by radioembolization with glass microspheres. Inclusion criteria are 1) BCLC stage A or B, 2) nodular tumor, 3) tumor size 3 cm or larger, and 4) Child-Pugh class A. Exclusion criteria are 1) vascular invasion, 2) extrahepatic metastssis, 3) infiltrative tumor, 4) Child-Pugh class B or C, and 5) tumor size less than 3 cm. Study population was divided into standard dose group (less than 180 Gy) and boosted dose group (greater than 180 Gy) according to mean estimated dose of perfused volume. Tumor response was evaluated by mRECIST at 1 month and 3 months after radioembolization. Local recurrence-free survival was analyzed by Kaplan Meier method and compared with log-rank test. 13 patients had single nodular tumor, and 15 patients had multiple nodular tumor. Mean tumor size is 7.9 cm (range, 3 cm ∼ 13.9 cm). Radioactive microspheres were infused into segmental or subsegmental hepatic arteries in most patients, and mean number of vials used is 4.3 (range, 2 ∼ 7 vials). Mean activity at administration was 4.17 GBq (range, 1.59 ∼ 9.15 GBq). Mean estimated dose of perfused volume was 199 Gy (range, 72 ∼ 411 Gy). 16 patients belonged to standard dose group, and 12 patients belonged to boosted dose group. Boosted dose group showed better tumor response than standard dose group (Table). Whereas 6 patients in standard dose group had local recurrence during follow-up, nobody in boosted dose group had local recurrence until August 2017 (p = 0.019). Boosted superselective radioembolization may reduce local recurrence in HCC patients of BCLC A/B stage.Tabled 11-Month Response3-Month ResponseStandard DoseBoosted DoseStandard DoseBoosted DoseCR2436PR8623SD2221PD3061 Open table in a new tab

Comparison of Outcome and Prognosis of 248 Elderly Patients with Acute Myeloid Leukemia Treated with Standard-Dose or Low-Intensity Induction Therapy

Acute myeloid leukemia (AML) is a disease of older adults, with a median onset age at about 65-70 years. The treatment outcome of AML appears to be poorer with the age increasing, in part due to the poor performance status, concomitant end-organ dysfunction, higher incidence of unfavorable cytogenetic findings, frequent involvement of a more immature leukemic precursor clone, multidrug resistance mediated by MDR1/P-glycoprotein, and the presence of antecedent hematopoietic disorders. Treatment of elderly patients with AML remains highly challenging and controversial. The overall survival rates at 5-year of ≥ 60 years old AML patients are still less than 20% by now. At present, standard-dose induction chemotherapy using a cytarabine plus idarubicin(IA regimen) or daunorubicin (DA regimen) was considered by most to be the most effective upfront AML induction therapy. However, there are still quite a number of elderly patients could not tolerate because of poor performance status and complications. Therefore, low-intensity chemotherapy, including CAG regimen, which combine low-dose cytarabine, aclacinomycin and granulocyte colony-stimulating factor(G-CSF), was used for those were not appropriate for receiving standard-dose chemotherapy. Here we retrospectively analyzed the outcome and prognosis of elderly patients with AML treated with standard-dose or low-intensity induction therapy. 248 elderly patients with acute myeloid leukemia(AML) who received standard-dose or low-intensity induction therapy were enrolled in this retrospective clinical study, 186 patients in standard-dose group with 144 in IA and 42 in DA, 62 cases in low-intensityCAG group. The maininclusion criteria included age ≥ 60 years old, ECOG performance status ≤ 2, without severe complication of heart, liver, kidney or other important organ. The patients received standard-dose or low-intensity induction regimen according to their performance status and patient preference. 144 patients received IA regimen(idarubicin 10mg/m2/d ,d1-3; cytarabine 100mg/m2, q12h, d1-5 or 7), 42 patients received DA regimen(daunorubicin 60mg/m2/d, d1-3; cytarabine 100mg/m2 q12h, d1-5 or 7), and 62 patients received CAG regimen (cytarabine 10mg/m2 q12h, d1-14; aclacinomycin 20mg qd, d1-4; G-CSF 200ug/m2 qd, d0-14, or until bone marrow recover). The median survival time was 9.2 months. 1-year , 3-year and 5-year overall survival(OS) were 42.2%, 18.9% and 13.5%, respectively. After first induction cycle, complete remission(CR) rate was 49.3% in IA group, 35.7% in DA group and 32.3% in CAG group (P = 0.046). The median OS for IA, DA and CAG group were 10.0 months, 9.7months and 7.5 months, respectively. The early mortality of induction therapy and recurrence rate of three regimens showed no difference. IA could improve the long term survival compared to CAG and DA, with 3-year OS: 23.5%,15.9% and 8.3%, respectively; 5-year OS: 19.4%, 6.3%, and 0, respectively (P<0.01). The 67.0% patients relapsed within 24 months, with median relapse time of 8.4 months, 14.6 months and 8.3 months for IA, DA and CAG regimen, respectively. Moreover, Kaplan-Meier analysis showed that 7 parameters were adverse prognostic factors for OS, including age ≥ 70 years old, poor ECOG performance status, unfavorable cytogenetics, non-remission after first induction cycle, white blood cell (WBC) counts ≥ 50×10^9/L, percentage of bone marrow (BM) blast ≥ 80% and higher lactic dehydrogenase (LDH) . Multivariable analysis identified non-remission after first induction cycle (HR = 6.141, 95%CI: 3.585-10.52, P = 0.000) and LDH ≥ 490 IU/L(HR = 1.001, 95%CI: 1.000-1.001, P = 0.000) as independent significantly prognostic factors for OS. In conclusion, Our present data showed that standard-dose IA regimen could improve CR rate and prolong the survival time compared to low-intensity CAG regimen, and CAG regimen still has a certain therapeutic effect for those unfit for intensive chemotherapy. Recurrence is still a serious problem for those who do not receive Allo-HSCT for consolidation after CR. All prognostic factors should be considered before induction therapy to make sure the patients receive the best individualized treatment. DisclosuresNo relevant conflicts of interest to declare.

Comparative efficacy of reduced or standard doses of lenograstim for peripheral blood stem cell mobilization and transplantation: A randomized study in patients undergoing autologous peripheral stem cell transplantation

7099 Background: 10 microg/kg/day of filgrastim and lenograstim have been recommended for mobilization of CD34+ cells without associated chemotherapy. However,in our previous randomized study we demonstrated that a 7.5 microg/kg/day dose of lenograstim has been as efficacious as 10 microg/kg/day of filgrastim. In this study, we investigated whether a reduced dose of lenograstim is equavalent to standard dose for autologous peripheral blood stem cell (PBSC) mobilization and transplantation. Methods: A total of 49 consecutive patients were randomized to either low dose (7.5 microg/kg/day, n = 24) or standard dose (10 microg/kg/day, n = 25) of lenograstim. These two groups were similar in regard to disease, sex, body weight, body surface area, conditioning regimens, previous chemotherapy cycles and radiotherapy. Each dose of lenograstim was administered for 4 consecutive days. The first PBSC apheresis was done on the 5th day. In the posttransplant period, lenograstim was given at 5 microg/kg/day until leukocyte engraftment. Results: Successful mobilization with the first apheresis, was achieved in 10/24 (42%) patients in low dose group versus 14/25 (56%) patients in standard dose group. No significant difference was seen in the median number of CD34+cells mobilized, as well as the median number of apheresis, median volume of apheresis, percentage of CD34+ cells, and CD34+ cell number. Leukocyte and platelet engraftments, the number of days requiring G-CSF and parenteral antibiotics, the number of transfusions were similar in both groups in the posttransplant period. Conclusions: Lenograstim 7.5 microg/kg/day is as efficious as Lenograstim 10 microg/kg/day for autologous PBSC mobilization and transplantation. No significant financial relationships to disclose.