Biweekly Oxaliplatin Plus S1 (SOX) As First Line Therapy For Advanced Or Metastatic Gastric Or Gastroesophageal Junction (G/GEJ) Caner In Chinese Elderly Patients: An Open-Label, Single-Arm, Phase 2 Study.

Background: SOX (oxaliplatin and S1 every 3 weeks) is one of the most common used first line chemotherapy for advanced or metastatic G/GEJ cancer in Asia, but with significant hematological and neurological toxicity. In China, the majority of gastric cancer patients are the middle-aged and elderly with dissatisfactory tolerance to 3-weekly chemotherapy. Therefore, we aimed to assess efficacy and safety of biweekly SOX as first line treatment in patients 60 years old or older with advanced G/GEJ cancer in a single arm phase 2 study. Methods: Oxaliplatin was administered intravenously on day 1 at 85 mg/m2. S-1 was given at 80, 100, 120 mg/day depending on body surface area of <1.25 m2, 1.25 to <1.5 m2, or ≥1.5 m2 two times daily on days 1-10, every 2 weeks. Eligible patients were aged 60 years old or older with histological or cytological diagnosis of advanced G/GEJ adenocarcinoma, had measurable disease according to the RECIST v 1.1 without previous treatment. The primary endpoint was objective response rate (ORR), and the secondary endpoints included progression free survival (PFS), overall survival (OS), disease control rate (DCR), duration of response (DOR) and safety. Results: Between May 2016 and Sep 2018, 42 patients were enrolled. Median follow-up time was 43.6 months. ORR and DCR were 52.4% and 85.7%, respectively. Median PFS was 4.6 months (95%CI 2.486-6.714). Median OS was 11.1 months (95%CI 8.001-14.199). The most common treatment-related adverse events (TRAEs) of any grade were thrombocytopenia (59.5%), neutropenia (57.1%), appetite loss (57.1%) and nausea (54.8%). Only two patients respectively suffered from grade 3 treatment-related neutropenia (1 patient, [2.4%]) and diarrhea (1 patient, [2.4%]). No other grade 3 or worse TRAEs occurred. Conclusions: First line biweekly SOX showed promising PFS and OS with a remarkable tolerance in advanced G/GEJ cancer patients 60 years old or older preliminary worth further evaluation.Trial registration: ClinicalTrials.gov ID: NCT04694404 (5/1/2021). This study was approved by the Ethical Committee of National Cancer Center/ National Clinical Research Center for Cancer/ Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, (17-048/1303).

Acute Toxicity of Paclitaxel Based Dose Dense and Conventional Neoadjuvant Chemotherapy in Locally Advanced Female Breast Cancer Patients

BACKGROUND Breast cancer is a systemic disease that requires treatment with surgery, chemotherapy, radiation, endocrine therapy and biological therapy. Neoadjuvant chemotherapy is the recent treatment of locally advanced breast cancer. The purpose of this study was to assess the acute toxicity of paclitaxel-based dose-dense and conventional neoadjuvant chemotherapy in locally advanced female breast cancer patients. METHODS In this study, neoadjuvant paclitaxel was given to a hundred locally advanced breast malignancies of female patients. Three weekly paclitaxel 200 mg/m2 ( 4 courses) was given for fifty patients and weekly paclitaxel 80 mg/m2 (10 courses) was given for fifty patients along with four-course of three weekly doxorubicin 50 mg/m2 given in both arms. Chemotherapy-induced acute toxicities in both arms were assessed weekly. RESULTS There was a significant increase in the incidence of anaemia in weekly chemotherapy patients at 7th week (28 % verse 10 %, P - value 0.022) and neutropenic infection at 11th week (28 % verse 10 %, P - value 0.022). There was a non-statistically significant increase in the incidence of leukopenia, thrombocytopenia and paraesthesia and myalgia in the weekly arm. There was a significant increase in the incidence of gastrointestinal toxicity like grade 3 stomatitis (at 4th - week), nausea and vomiting (at 4th, 7th, and 11th week ) in three weekly chemotherapy patients. CONCLUSIONS In this study, acute neurological and haematological toxicities were more in the weekly neoadjuvant chemotherapy arm and acute gastrointestinal toxicities were more in the three weekly neoadjuvant chemotherapy arm. KEYWORDS Acute Toxicity, Neoadjuvant Paclitaxel Chemotherapy, Locally Advanced Breast Malignancy.

Weekly chemotherapy as first line treatment in frail head and neck cancer patients in the immunotherapy era

Objective First-line therapy for metastatic squamous cell carcinoma of the head and neck (R/M HNSCC) has been revolutionized by the introduction of anti-checkpoint monoclonal antibodies, which have shown a significant improvement in overall survival (OS) gaining approval in a first line setting. Efficacy and safety of first-line weekly chemotherapy, compared to 3-weeks treatment, was retrospectively evaluated in a frail patient population with R/M HNSCC with the aim to evaluate its role as part of a personalized first-line approach. Methods A total of 124 patients with locally incurable R/M HNSCC receiving weekly (21) or three-weekly (103) chemotherapy plus cetuximab in a first line setting from December 2010 to September 2020 were retrospectively reviewed. Treatment outcomes in terms of objective response rate (ORR), progression-free survival (PFS), overall survival (OS) and toxicities were analysed. Results Patients in the three-week subgroup were ECOG PS 0 (39) and 1 (64) while patients in weekly group (21) were all PS 2. No significant differences were reported in terms of age, sex, smoking and previous alcohol abuse considering the two distinct subgroups. Moreover, no statistically significant difference was found in PFS and OS between the two treatment subgroups. The response rate was 35% (36 patients) and 34% (7 patients) in three-week and weekly treatment group, respectively. Seventy patients (68%) in the three-week group experienced chemotherapy-related toxicities, predominantly G3. In the weekly group a predominantly low-grade toxicity was found in a lower number of patients (52%). Conclusion The weekly schedule appears to be an active and safe strategy in frail patients with R/M HNSCC. Based on these data, a weekly schedule could be considered as a first line treatment in all frail patients excluded from pembrolizumab treatment and a study on the combination of weekly chemotherapy and immunotherapy should be performed.

Weekly Chemotherapy as First Line Treatment in Frail Head and Neck Cancer Patients in the Immunotherapy Era

Objective: First-line therapy for metastatic squamous cell carcinoma of the head and neck (R/M HNSCC) has been revolutionized by the introduction of anti-checkpoint monoclonal antibodies, that have shown a significant improvement in overall survival (OS) gaining the approval in first line setting. Efficacy and safety of first-line weekly chemotherapy, compared to three-weeks treatment, was retrospectively evaluated in frail patients’ population with R/M HNSCC with the aim to evaluate its role as part of a personalized first-line approach.Methods: A total of 124 patients with locally incurable R/M HNSCC receiving weekly (21) or three-weekly (103) chemotherapy plus cetuximab in first line setting from December 2010 to September 2020 were retrospectively reviewed. Treatment outcomes in terms of objective response rate (ORR), progression-free survival (PFS), OS and toxicities were analyzed.Results: Patients in the three-week subgroup were ECOG PS 0 (39) and 1 (64) while patients (21) in weekly group were all PS 2. No significant differences were reported in terms of age, sex, smoking and previous alcohol abuse considering the two distinct subgroups. Moreover, no statistically significant difference was found in PFS and OS between the two treatment subgroups. The response rate was 35 % (36 patients) and 34 % (7 patients) in three-week and weekly treatment group, respectively. Seventy patients (68%) in the three-week group experienced chemotherapy-related toxicities, predominantly G3. In the weekly group a predominantly low-grade toxicity was found in a lower number of patients (52%).Conclusion: The weekly schedule appears an active and safe strategy in frail patients with R/M HNSCC. Based on our data, the weekly schedule could currently be considered in all frail patients and study of combination of weekly chemotherapy and immunotherapy should be performed.

Use of cetuximab added to weekly chemotherapy to improve progression-free survival in patients with recurrent metastatic head and neck squamous cell carcinoma after progression on immune checkpoint inhibitors.

6038 Background: Immune checkpoint inhibitors (ICI) are currently approved in the treatment of patients (pts) with recurrent-metastatic (R/M) head and neck squamous cell carcinoma (HNSCC). The majority of pts will progress on ICI. Little is known regarding the best treatment approach for this patient population. We previously showed that the combination of weekly carboplatin, paclitaxel and cetuximab was associated with reduced risk of grade 3/4 toxicities, which makes it an ideal regimen in this setting. Here; we report the outcomes of pts with R/M HNSCC who were treated with chemotherapy alone vs weekly chemotherapy plus cetuximab after progression on ICI. Methods: Between January 15th 2016 and April 9th 2020, 154 pts who progressed on ICI were analyzed. Among these pts, 64 had received subsequent systemic therapy and met the inclusion criteria. Progression Free Survival (PFS) was defined as the time elapsed between initiation of subsequent chemotherapy and tumor progression or death. Overall Survival (OS) was defined as the time elapsed between initiation of subsequent chemotherapy to death. Descriptive statistics and Cox regression were used to explore study variables. Results: 64 pts received subsequent chemotherapy after progression on ICI. 28 pts (44%) received a combination of weekly chemotherapy plus cetuximab. This regimen included carboplatin AUC 1.5, paclitaxel 45 mg/m2, and cetuximab loading dose of 400mg/m2 followed by weekly dose of 250 mg/m2. 36 pts (56%) received chemotherapy alone without cetuximab. These regimens included capecitabine, afatinib, and gemcitabine, among others. Sex: 51 males (80%), 13 females (20%), age (median): 61 (IQR: 53-66), tumor site: oropharynx 32 (50%), oral cavity 11 (17%), larynx 8 (12%), other sites 13 (21%). P16 status: negative 36 (56%), positive 28 (44%). Prior ICI drug: pembrolizumab 34 (53%), nivolumab 26 (41%), ipilimumab + nivolumab 4 (6%). Median follow up: 9 months (IQR: 5-13). Overall response rate: weekly chemotherapy plus cetuximab 32%, chemotherapy alone 22% (p = 0.4). Pts who received chemotherapy alone had a median PFS of 3.2 months (CI: 2-5) vs 5.6 months (CI: 4.3-10.1) in the weekly chemotherapy plus cetuximab group. After adjusting for p16 status and prior ICI drug, PFS was improved in the group that received weekly chemotherapy plus cetuximab vs. chemotherapy alone (HR: 0.52; CI: 0.28-0.98; p = 0.042). Median OS was 10 months (CI: 8.5-NR) in the weekly chemotherapy plus cetuximab group vs 8.7 months (CI: 5.7-13.8) in the chemotherapy alone group (HR: 0.84; CI: 0.4-1.8; p = 0.8). Conclusions: Pts with R/M HNSCC who progressed on ICI experience longer PFS with the addition of cetuximab to weekly chemotherapy. Further investigation in a larger cohort of pts is needed to fully assess the impact on survival for this treatment combination.

Preliminary data on antitumor activity of extracorporeal subtraction of soluble TNFRs to unleash the activity of endogenous TNFα combined with chemotherapy in treatment-refractory, advanced, triple-negative breast cancer patients.

e13052 Background: Tumor necrosis factor-alpha (TNFα) is a pleiotropic cytokine, with known antitumor activity, produced mainly by activated immune cells. Cancer cells neutralize TNFα by shedding soluble TNF receptors 1&2 (sTNFRs), which act as TNFα-binding decoys. In addition, sTNFRs can directly promote proliferation, survival, and chemoresistance of cancer cells by binding to membrane-bound TNFα and initiating retrograde signaling. Therefore, the reduction of systemic and intratumoral concentrations of sTNFRs represents a novel and unique strategy to reinvent the anticancer use of TNFα. Methods: In this clinical trial (CP7-005; NCT04004910) we evaluated extracorporeal Immunopheresis (subtractive apheresis) with the novel LW-02 immunoadsorption column in advanced chemo-refractory metastatic triple-negative breast cancer (mTNBC). The LW-02 column, which utilizes a proprietary, recombinant single-chain TNFα as the sTNFR-scavenger ligand has received FDA breakthrough designation for cancer treatment. Here we present data on the second cohort of mTNBC patients treated with LW-02 combined with weekly chemotherapy; Cohort 1 (n=10) evaluated Immunopheresis as monotherapy only. In Cohort 2, patients are treated with LW-02 immunopheresis only in week 1 (3 treatments involving processing of 2 plasma volumes (2PV)). From week 2, paclitaxel [60 mg/m2]+carboplatin[AUC2] combination is administered once weekly along with LW-02 immunopheresis (2PV 3x/week). Results: To date, 7 mTNBC patients who failed ≥2 lines of chemotherapy (median=3; 2-5) in the advanced setting have been enrolled. The combination of LW-02 column immunopheresis and chemotherapy resulted in a 29% ORR (1CR, 1PR). In 5 patients who completed at least 4 weeks of treatment, the ORR was 40%. Median OS in the whole population as of this report is 13.3 weeks, and 18.4 weeks in the patients treated for >4 weeks. Treatment-related AEs occurred in most patients; however, most being attributed to chemotherapy - CTCAE G3-4 in 71% (anemia – 71%, neutropenia 29%, thrombocytopenia 29%). Immunopheresis-related G3-4 AEs were CVC complications (29%), hypophosphatemia (14%) and hypercalcemia (14%). Conclusions: The combination of LW-02-column immunopheresis and weekly chemotherapy procedure was shown to be generally safe and provided early, promising signs of antitumor activity in heavily pretreated mTNBC patients with short life expectancy. Further clinical evaluation of the antitumor activity of LW02-based immunopheresis combined chemotherapy is ongoing; however, due to myelotoxicity, the chemotherapy regimen will be adapted accordingly. Clinical trial information: NCT04004910.

Definitive Chemoradiation with Concurrent Weekly Cisplatin in the Treatment of Esophageal Squamous Cell Carcinoma – A Simplistic Approach

Purpose: Chemoradiation is the standard of care in locally advanced/ inoperable esophageal squamous cell cancer (ESCC). Though combination chemotherapy with Cisplatin and 5-Fluorouracil is the standard, it has low compliance due to toxicities and prolonged treatment time. Hence there is a window of opportunity to explore a safer chemotherapy regimen without compromising the treatment outcome. Methods: 55 patients of ESCC who were treated with definitive External Beam Radiotherapy (EBRT) to a dose of 50.4 – 59.4 Gray and concurrent weekly Cisplatin (or Carboplatin) were retrospectively evaluated for treatment efficacy and outcomes. 2 year Overall Survival (OS) and Progression Free Survival (PFS) were evaluated. Prognostic variables were assessed with respect to OS in Univariate analysis. Results: Median age at presentation was 58 years. 29 (53%) had lesion in the upper third of esophagus. 40 (72%) had T3 disease and 31 (56%) were node positive. All patients (100%) completed planned radiotherapy dose. 54 (98%) received 4 or more cycles of weekly chemotherapy. Mean overall treatment time was 43 days. Only 7 patients (12.7%) had grade 3 or more acute toxicity. 36 (65.5%) had complete response. At median follow-up of 13.7 months, the median OS was 15.2 months and 2 year OS was 42.6%. On univariate analysis, patients with comorbidities and lower third lesion had poor OS (p=0.016 and p=0.002). Stage II disease and complete response to treatment showed better OS (p=0.02 and p=0.00). Conclusion: Radical chemoradiation with weekly Cisplatin in ESCC is a simple and effective regimen which needs to be explored in larger trials.

Compression therapy using surgical gloves does not prevent paclitaxel-induced peripheral neuropathy: results from a double-blind phase 2 trial

Background Chemotherapy-induced peripheral neuropathy (CIPN) is a common adverse effect of paclitaxel (PTX). There is no known prophylactic measure, although there are some reports of prevention with compression therapy using surgical gloves. On account of its predominantly subjective symptoms, it is difficult to exclude bias when assessing for CIPN. In this study, we assessed the effectiveness of the same procedure for the prevention of paclitaxel-induced PN based on a double-blind study design. Methods The patients with early and recurrent breast cancer (with no prior PTX exposure) initiating weekly chemotherapy with PTX 80 mg/m2 were enrolled. Each patient donned two gloves on each hand at every PTX infusion. Two one-size-smaller gloves were donned on one hand (study side) and two normal-size gloves were donned on the other hand (control side) during 90 min from 30 min before the infusion to 30 min after the end of the infusion. Study side are blind for both patients and assessing physicians according to determination of the study side by research nurses in the chemotherapy unit. The primary outcome was the difference in the frequency of CIPN (motor/sensory) determined by the physician using the common terminology criteria for adverse events (CTCAE v4.0), with an evaluation at each cycle of PTX infusion. McNemar test was used to assess the primary outcome. Results Between July 2017 and November 2018, 56 patients were enrolled and 49 patients were evaluated. Overall, Grade ≥ 2 PN (sensory) was observed in 30.6 and 36.7% in the study and control sides, respectively (McNemar p = 0.25). PN (motor) was observed in 4.1 and 6.1% in the study and control sides, respectively (McNemar p = 1.0). Conclusion Surgical glove compression therapy showed no statistically significant effect on the incidence of PTX-induced PN. Trial registrations This study was registered with the University Hospital Medical Information Network (UMIN) Clinical Trials Registry managed by the National University Hospital Council of Japan (UMIN000027944). Registered 26 June 2017.

Impact of Factors on Acute Radiation Oral Mucositis for Nasopharyngeal Carcinoma Patients Treated with Concurrent Intensity-Modulated Radiation Therapy and Chemoradiotherapy:A Retrospective Study

Background To retrospectively studied the medical records in the latest 4 years in order to investigate the occurrence and influencing factors of radiation-induced oral mucositis in patients with nasopharyngeal carcinoma treated with concurrent intensity-modulated radiation therapy and chemoradiotherapy. Methods Between January 2014 and December 2018, 262 patients with non-metastatic nasopharyngeal carcinoma treated with concurrent intensity-modulated radiation therapy and chemoradiotherapy were enrolled in the study.The patients' age,gender,body mass index,smoking,diabetes,clinical stage, hematological parameters before radiotherapy before radiotherapy(leukocyte count,erythrocyte count,hemoglobin level,platelet count,lymphocyte count, neutrophil count),PGTV, PCTV1, PCTV2, induction chemotherapy, concurrent chemotherapy interval(weekly or three-weekly chemotherapy) and the concurrent chemotherapeutic drugs (single cisplatin or single lobaplatin or docetaxel plus cisplatin regimen) were examined, and the associations of variables with oral mucositis were analyzed by multivariate logistic regression analysis. Results Only platelet count before radiotherapy is the risk factor for grade 2 and higher acute oral mucositis(p = 0.028) with an odds ratio of 1.005 (95% CI: 1.001–1.009).There was no difference in the risk of grade 2 and higher oral mucositis between the single platinum regimen and docetaxel plus cisplatin regimen.The study also found similar responses to oral mucositis between weekly regimen and three-weekly regimen. Conclusion The present retrospective study demonstrated that certain factor may predispose patients with with nasopharyngeal carcinoma treated with concurrent intensity-modulated radiation therapy and chemoradiotherapy to develop oral mucositis.

Weekly Etoposide and Platinum in Small-Cell Lung Cancer: Hope and Scope for Fragile Patients

Introduction Small-cell lung cancer (SCLC) is an aggressive and chemo-sensitive disease. Many patients present in an advanced stage and with a poor performance status (PS). In such a condition, the treatment dilemma due to poor condition advocates alternative treatment approach rather than standard chemotherapy. One way of usual practice is to split the chemotherapy into a weekly schedule. However, there is limited data regarding the actual benefit of weekly chemotherapy. We hypothesize that a weekly chemotherapy with etoposide/platinum combination will be feasible and safe in patients of advanced-stage SCLC with poor PS. Objectives This study was aimed to determine whether weekly etoposide/platinum chemotherapy is a safe option for patients with advanced stage, poor PS, and SCLC who are otherwise unfit for systemic anticancer therapy. Materials and Methods We retrospectively analyzed the data of SCLC patients presented to our center from July 2018 to September 2020. We analyzed that treatment, survival, and clinical benefit data. We also analyzed the benefit of weekly etoposide/platinum in otherwise unfit for chemotherapy. Results One hundred and fifty patients of lung cancer presente to our department between July 2018 and September 2020; SCLC constituted 34% (53 cases). In SCLC patients, the median overall survival was 2.5 months. Fourteen (26%) patients with SCLC were unable to start any oncological intervention. Ten (19%) patients could receive only one cycle of standard 3 weekly chemotherapy. Five patients with an advanced-stage SCLC and an ECOG-PS of 4, otherwise unfit for any systemic anticancer therapy, were started on weekly chemotherapy with etoposide (60–80 mg/m2) and carboplatin (AUC 2). Four patients demonstrated a partial response (PR) while one demonstrated stable disease (SD) after 9 weeks of therapy. Improvement in PS was noted in all patients. Median progression-free survival (PFS) and overall survival (OS) were 137 and 164 days, respectively. Two patients died of disease progression, one died of massive pulmonary embolism, while two were alive and continuing on the same protocol. Conclusion The weekly etoposide and platinum chemotherapy is a practical and feasible treatment option in patients who are otherwise fragile and unfit for standard-dose chemotherapy.