Metronomic Therapy Research Articles

Role of metronomic therapy for advanced oral cancers and predictors of response: Multi-institutional feasibility study.

In an era of targeted therapies, patients with cancer in resource-constraint countries continue to struggle to find affordable care. The present study is a multicenter prospective single-arm study. Patients with expected delay in surgery, unresectable or metastatic cancers, and patients not suitable for surgery or conventional chemotherapy were included. Oral methotrexate 15 mg/m2 once a week and oral celecoxib 200 mg twice daily was used for metronomic therapy. At 8 weeks, a clinically complete response was seen in 2.5%, partial response in 46.6%, stable disease in 39.8%, and disease progression in 11%. Size less than 4cm, alveolobuccal subsite, and well-differentiated histology were significantly associated with no disease progression. Constraint-adapted approach of using methotrexate and celecoxib is economical with good compliance, minimal toxicity, and good efficacy. It is feasible for use in diverse settings. Individualized selection of patients based on response predictors may maximize metronomic therapy's benefit.

Metronomic Anti-Cancer Therapy: A Multimodal Therapy Governed by the Tumor Microenvironment.

Simple SummaryMetronomic chemotherapy with different mechanisms of action against cancer cells and their microenvironment represents an exceptional holistic cancer treatment. Each type of tumor has its own characteristics, including each individual tumor in each patient. Understanding the complexity of the dynamic interactions that take place between tumor and stromal cells and the microenvironment in tumor progression and metastases, as well as the response of the host and the tumor itself to anticancer therapy, will allow therapeutic actions with long-lasting effects to be implemented using metronomic regimens. This study aims to highlight the complexity of cellular interactions in the tumor microenvironment and summarize some of the preclinical and clinical results that explain the multimodality of metronomic therapy, which, together with its low toxicity, supports an inhibitory effect on the primary tumor and metastases. We also highlight the possible use of nano-therapeutic agents as good partners for metronomic chemotherapy.The concept of cancer as a systemic disease, and the therapeutic implications of this, has gained special relevance. This concept encompasses the interactions between tumor and stromal cells and their microenvironment in the complex setting of primary tumors and metastases. These factors determine cellular co-evolution in time and space, contribute to tumor progression, and could counteract therapeutic effects. Additionally, cancer therapies can induce cellular and molecular responses in the tumor and host that allow them to escape therapy and promote tumor progression. In this study, we describe the vascular network, tumor-infiltrated immune cells, and cancer-associated fibroblasts as sources of heterogeneity and plasticity in the tumor microenvironment, and their influence on cancer progression. We also discuss tumor and host responses to the chemotherapy regimen, at the maximum tolerated dose, mainly targeting cancer cells, and a multimodal metronomic chemotherapy approach targeting both cancer cells and their microenvironment. In a combination therapy context, metronomic chemotherapy exhibits antimetastatic efficacy with low toxicity but is not exempt from resistance mechanisms. As such, a better understanding of the interactions between the components of the tumor microenvironment could improve the selection of drug combinations and schedules, as well as the use of nano-therapeutic agents against certain malignancies.

Efficacy, Safety and Cost Effectiveness of Metronomic Low Dose Versus Intermittent High Dose Capecitabine in Metastatic Breast Cancer

AIM: The aim of the study is to compare the toxicity and cost-effectiveness between metronomic and intermittent capecitabine as maintenance therapy in female patients with metastatic breast cancer. PATIENTS AND METHODS: All metastatic breast cancer patients with HER2 negative were included. The whole study population received six cycles of Docetaxel/Capecitabine then patients were randomized to either continuous (650 mg/m2 twice daily continuous) or intermittent Capecitabine (1000 mg/m2 twice daily every 21 days) as maintenance. RESULTS: The study included 51 patients, 26 in the metronomic arm and 25 in the continuous. The median number of maintenance cycles, as well as the partial response, was higher in the continuous (18 vs. 13 cycles, p: 0.031; p: 0.038). The continuous arm was tolerable with significant less Grade 3 and 4 toxicity regarding nausea, vomiting, hand and foot syndrome, neutropenia, and elevated liver enzymes. (p: 0.03, 0.045, 0.051, 0.048, 0.06, respectively). On multivariate analysis, only patients receiving treatment as first-line had a better clinical response (p: 0.03) especially in the triple-negative group (p: 0.07). The metronomic therapy was more cost-effective with a 35.9% reduction of cost. ($ 746 vs. $1164). The progression-free survival and overall survival were not significant between the two groups. CONCLUSION: Metronomic continuous capecitabine proved to be less toxic and more cost-effective.

Prognostic Value of EGFR Expression for Patients With Stage III Colorectal Cancer Receiving Fluoropyrimidine Metronomic Maintenance Therapy After Radical Resection and Adjuvant Oxaliplatin-Based Chemotherapy

This study evaluated the survival effects of metronomic maintenance therapy with oral fluoropyrimidine in patients with stage III colorectal cancer (CRC) according to epidermal growth factor receptor (EGFR) expression. We enrolled 197 patients with stage III CRC who had undergone radical resection and FOLFOX regimen adjuvant chemotherapy. The clinicopathological features and effects of metronomic maintenance therapy with oral capecitabine (daily dose of 850 mg/m2, twice daily, on days 1–14 every 3 weeks for 6 months) on survival according to treatment group and EGFR expression were analyzed. By conducting an in vitro cell line study and in vivo study through knockout of the EGFR gene, we analyzed the capacities of cell proliferation and migration. Relapse and survival were significantly more common in the FOLFOX group. Metronomic maintenance therapy was a significantly independent associated factor of relapse and survival as well as a prognostic factor of disease-free survival and overall survival. Significant intergroup differences in survival were only observed in patients with positive EGFR expression. Thus, our findings suggest EGFR expression is a prognostic factor in patients with stage III CRC receiving metronomic maintenance therapy. Analysis of EGFR expression in these patients helps identify potential candidates who may receive the optimal survival benefit from metronomic maintenance therapy.

360P Metronomic temozolomide therapy in heavily pretreated patients with recurrent glioblastoma: A large mono-institutional retrospective study

Glioblastoma (GBM) is the most common and aggressive primary brain cancer. Despite advances in surgical and first-line treatment, all pts relapse. The aim of this study is to evaluate the benefit of metronomic Temozolomide (mTMZ) for recurrent GBM.

Molecular Iodine/Cyclophosphamide Synergism on Chemoresistant Neuroblastoma Models.

Neuroblastoma (Nb), the most common extracranial tumor in children, exhibited remarkable phenotypic diversity and heterogeneous clinical behavior. Tumors with MYCN overexpression have a worse prognosis. MYCN promotes tumor progression by inducing cell proliferation, de-differentiation, and dysregulated mitochondrial metabolism. Cyclophosphamide (CFF) at minimum effective oral doses (metronomic therapy) exerts beneficial actions on chemoresistant cancers. Molecular iodine (I2) in coadministration with all-trans retinoic acid synergizes apoptosis and cell differentiation in Nb cells. This work analyzes the impact of I2 and CFF on the viability (culture) and tumor progression (xenografts) of Nb chemoresistant SK-N-BE(2) cells. Results showed that both molecules induce dose-response antiproliferative effects, and I2 increases the sensibility of Nb cells to CFF, triggering PPARγ expression and acting as a mitocan in mitochondrial metabolism. In vivo oral I2/metronomic CFF treatments showed significant inhibition in xenograft growth, decreasing proliferation (Survivin) and activating apoptosis signaling (P53, Bax/Bcl-2). In addition, I2 decreased the expression of master markers of malignancy (MYCN, TrkB), vasculature remodeling, and increased differentiation signaling (PPARγ and TrkA). Furthermore, I2 supplementation prevented loss of body weight and hemorrhagic cystitis secondary to CFF in nude mice. These results allow us to propose the I2 supplement in metronomic CFF treatments to increase the effectiveness of chemotherapy and reduce side effects.

The prolonged clinical benefit with metronomic chemotherapy (VEX regimen) in metastatic breast cancer patients.

Metronomic chemotherapy is a treatment option for metastatic breast cancer (MBC) patients who require prolonged disease control without cumulative toxicity. Data available on the efficacy and tolerability of prolonged usage of metronomic therapy are limited. We analyzed patients with MBC, enrolled in a clinical trial, who obtained a prolonged clinical benefit for a duration of at least 12 months with vinorelbine 30 or 40 mg orally three times a week, cyclophosphamide 50 mg daily and capecitabine 500 mg three times a day (VEX regimen). The patients were treated at the European Institute of Oncology, Milan. We identified 67 MBC patients. The median age before starting the VEX regimen was 53 years. There were 59 patients (88%) who had hormone-receptors positive and HER2 negative BC. We had 37 patients who received VEX as the first-line treatment for MBC, while 30 patients were pretreated. The objective response rate was 49% (95% CI, 37-62). The median duration of VEX treatment after the first year was 14 months (min-max range 0.3-81.3 months). The progression-free survival at 3 years was 25.4% (95% CI, 15.7-36.2) and at 4 years was 18.5% (95% CI, 10.1-28.8 time 0 corresponds to 1 year after starting VEX). A total of 25 patients required a dose reduction, 7% of patients experienced G3 hand and foot syndrome. Metronomic VEX regimen can induce prolonged clinical benefit in MBC. On the basis of this long-term safety evaluation, there is no evidence of specific cumulative or delayed toxicities with metronomic chemotherapy.

Oral Metronomic Maintenance Therapy Can Improve Survival in High-Risk Neuroblastoma Patients Not Treated with ASCT or Anti-GD2 Antibodies.

Simple SummaryLow-dose metronomic chemotherapy has anti-angiogenic activity and inhibits tumor growth. Therefore, we investigated the benefits of low-dose metronomic maintenance therapy (MT) in high-risk neuroblastoma (NB) patients who are unable to undergo autologous stem cell transplantation (ASCT) or anti-GD2 antibody therapy. A total of 217 high-risk NB patients were enrolled. One hundred and eighty-five (85%) had a complete/very good partial remission/partial remission (CR/VGPR/PR) to treatment, of them, 167 patients with stage 4, that did or did not receive oral metronomic MT, 3 years of event-free survival (EFS) were 42.5% versus 29.4%, and overall survival (OS) was 71.1% versus 59.4%, respectively. Totally, 117 high-risk patients with oral metronomic MT had an EFS rate of 42.7%. The results were similar to those of ASCT from other studies. The toxicities of metronomic MT were lower. Our study showed that oral metronomic MT is an optimal option for high-risk NB patients without ASCT or anti-GD2 antibody therapy.Despite aggressive treatment, the prognosis of high-risk NB patients is still poor. This retrospective study investigated the benefits of metronomic maintenance treatment (MT) in high-risk NB patients without ASCT or GD2 antibody therapy. Patients aged ≤ 21 years with newly diagnosed high-risk NB were included. Patients with complete/very good partial remission (CR/VGPR/PR) to conventional treatment received, or not, oral metronomic MT for 1 year. Two hundred and seventeen high-risk NB patients were enrolled. One hundred and eighty-five (85%) had a CR/VGPR/PR to conventional treatment, of the patients with stage 4, 106 receiving and 61 not receiving oral metronomic MT, and the 3-year event-free survival (EFS) rate was 42.5 ± 5.1% and 29.6 ± 6%, respectively (p = 0.017), and overall survival (OS) rate was 71.1 ± 4.7% and 59.4 ± 6.4%, respectively (p = 0.022). A total of 117 high-risk patients with oral metronomic MT had EFS rate of 42.7 ± 4.8%. The toxicity of MT was mild. For high-risk NB patients without ASCT or anti-GD2 antibody therapy, stage 4, MYCN amplication and patients with stage 4 not receiving oral metronomic MT after CR/VGPR/PR were independent adverse prognostic factors. Oral metronomic MT can improve survival in high-risk NB patients in CR/VGPR/PR without ASCT or anti-GD2 antibodies therapy.

Advances in pharmacotherapy for head and neck cancer

ABSTRACT Introduction: Head and neck squamous cell carcinoma (HNSCC) is one of the most common cancers worldwide and is a leading cause for cancer-related mortality. This review attempts to give a comprehensive summary of the recent developments in pharmacotherapeutic options for locally advanced/metastatic HNSCC. Areas covered: In this review, the authors conducted a systematic literature search for published articles on HNSCC in the PubMed database using the keywords ‘head and neck squamous cell carcinoma or HNSCC,’ ‘targeted therapy,’ ‘immunotherapy.’ The search was restricted to meta-analyses, clinical trials, practice guidelines, and abstract presentations at international meetings. The final search encompassed articles published from 2010 to 2021. Articles published in languages other than English were excluded. Expert opinion: Immune checkpoint inhibition has been the most significant advance in the treatment of R/M HNSCC. Oral metronomic therapy has emerged as an important therapeutic option for low to middle-income countries. H-RAS inhibition is one of the most promising areas of research.

Recurrent liver metastasis in ovarian cancer

The most common sites of metastasis in ovarian cancer is liver, peritoneum, and lymph nodes resulting from hematogenous spread or secondary to liver parenchymal invasion from perihepatic peritoneal metastases. The case was retrieved from routine reporting at our hospital. A 34-year-old female presented with lump in left side of abdomen for six months. Ultrasonography showed Left complex tubo-ovarian mass. Serum level of CA125 was 19.8U/mL. Upfront surgery was done. Histopathology showed malignant lesion, positive for WT1, P53 & CK7 and negative for CK 20. Retroperitoneal lymph nodes and omentum were involved. The cases was diagnosed as epithelial ovarian cancer, high grade papillary serous cyst adenocarcinoma stage III. Three months after surgery repeat contrast enhanced computed tomography showed lung and liver metastasis lymphadenopathy. Patient was given 6 cycles of paclitaxel + carboplatin to achieve complete clinical response (CR). Lesions of lung, liver & lymph node subsided. She spent 33 months of treatment free interval, after which lymph node enlargement was noticed and its fine needle aspiration cytology showed metastasis. Patient was put on to oral metronomic therapy with etoposide, cyclophosphamide, and celecoxib (COX-2 inhibitor) for 8 months, which showed CR. Again after 4 months, lesion in liver reappeared with raised CA 125, suggesting second relapse. The patient is on oral metronomic therapy till date with improved clinical condition. This study highlights the need of early diagnosis, adjuvant chemotherapy with frequent follow up in this case. Liver is an early site for metastasis. Second relapse in also not uncommon.

P-178 Low cost, oral, metronomic therapy protocol in locally advanced oral cancers in Eastern India – Feasibility study

P-178 Low cost, oral, metronomic therapy protocol in locally advanced oral cancers in Eastern India – Feasibility study

Vinorelbine in treatment of non-small cell lung cancer

Chemotherapy is important part of the systemic treatment of non-small cell lung cancer (NSCLC). Vinorelbine has proven its effectiveness in adjuvant therapy, as part of chemoradiotherapy programs, and in the treatment of metastatic disease. The oral form of the drug is significantly more convenient to use and can be used not only in standard dosage regimens (both in monotherapy and in combination with platinum derivatives), but also in metronomic therapy, which provides for more frequent administration of vinorelbine in smaller single doses. Oral vinorelbine has been shown to be highly effective and safe in various patient populations, including subgroups of elderly and patients with ECOG2, and can be widely used in various stages of NSCLC treatment.

Metronomic Therapy in Oral Squamous Cell Carcinoma.

Metronomic therapy is characterized by drug administration in a low-dose, repeated, and regular manner without prolonged drug-free interval. The two main anticancer mechanisms of metronomic therapy are antiangiogenesis and immunomodulation, which have been demonstrated in several delicate in vitro and in vivo experiments. In contrast to the traditional maximum tolerated dose (MTD) dosing of chemotherapy, metronomic therapy possesses comparative efficacy but greatlydecreases the incidence and severity of treatment side-effects. Clinical trials of metronomic anticancer treatment have revealed promising results in a variety cancer types and specific patient populations such as the elderly and pediatric malignancies. Oral cavity squamous cell carcinoma (OCSCC) is an important health issue in many areas around the world. Long-term survival is about 50% in locally advanced disease despite having high-intensity treatment combined surgery, radiotherapy, and chemotherapy. In this article, we review and summarize the essence of metronomic therapy and focus on its applications in OCSCC treatment.

Oral tegafur-uracil as a metronomic therapy in stage IVa and IVb cancer of the oral cavity

PurposeThis study aimed to evaluate the impact of accumulated oral tegafur-uracil (UFUR) as maintenance chemotherapy on overall survival (OS) and disease-free survival (DFS) rates after definitive treatment for non-distant metastatic stage IV cancer of the oral cavity. Materials and methodsThis retrospective, hospital center-based study analyzed data of patients diagnosed with stage IVa and IVb cancer of the oral cavity who underwent surgical resection and concurrent chemoradiotherapy (CCRT) obtained from a database between October 2008 and December 2014. ResultsForty-two patients were treated with CCRT (non-UFUR group); the remaining 51 patients received the same regimen, followed by additional oral UFUR (UFUR group). For all study patients, the 3-year DFS rates were 53.05% and 35.41% in the UFUR and non-UFUR groups, respectively (p = 0.011), while the 3-year OS rates were 74.96% and 48.47%, respectively (p = 0.001). ConclusionsAdding UFUR to CCRT significantly improved the DFS and OS rates in patients with non-distant metastatic stage IV cancer of the oral cavity.

Breast cancer: Muscarinic receptors as new targets for tumor therapy.

The development of breast cancer is a complex process that involves the participation of different factors. Several authors have demonstrated the overexpression of muscarinic acetylcholine receptors (mAChRs) in different tumor tissues and their role in the modulation of tumor biology, positioning them as therapeutic targets in cancer. The conventional treatment for breast cancer involves surgery, radiotherapy, and/or chemotherapy. The latter presents disadvantages such as limited specificity, the appearance of resistance to treatment and other side effects. To prevent these side effects, several schedules of drug administration, like metronomic therapy, have been developed. Metronomic therapy is a type of chemotherapy in which one or more drugs are administered at low concentrations repetitively. Recently, two chemotherapeutic agents usually used to treat breast cancer have been considered able to activate mAChRs. The combination of low concentrations of these chemotherapeutic agents with muscarinic agonists could be a useful option to be applied in breast cancer treatment, since this combination not only reduces tumor cell survival without affecting normal cells, but also decreases pathological neo-angiogenesis, the expression of drug extrusion proteins and the cancer stem cell fraction. In this review, we focus on the previous evidences that have positioned mAChRs as relevant therapeutic targets in breast cancer and analyze the effects of administering muscarinic agonists in combination with conventional chemotherapeutic agents in a metronomic schedule.

Pazopanib based oral metronomic therapy for platinum resistant/refractory epithelial ovarian cancer: A phase II, open label, randomized, controlled trial

BackgroundTreatment of patients with platinum resistant/refractory epithelial ovarian cancer (EOC) is an unmet need. We evaluated the role of oral metronomic therapy in this setting. Patients and methodsBetween October 2017 and September 2019 seventy five patients with platinum resistant/refractory EOC were enrolled. Patients received oral etoposide (50 mg, day 1 to 14, cyclophosphamide 50 mg, day 1 to 28, every 4 weeks (Arm A, n = 38). Patients in Arm- B (n = 37) received Pazopanib (400 mg once daily) in addition to etoposide and cyclophosphamide. Quality of life (QoL) was evaluated using the EORTC questionnaire. Serum VEGF and PDGF were estimated at baseline, after 3rd and 6th cycle. The primary endpoint was progression free survival (PFS). Secondary endpoints were overall survival (OS), toxicity and QoL. ResultsPatients characteristics were well matched. Median PFS was higher in arm B, 5.1 months (95% CI 3.13 to10.33) compared to 3.4 months (95% CI 3.0 to 6.53) in arm A, p = 0.045. Median OS has ‘not reached’ in Arm B compared to 11.2 months (95% CI, 5.66 - not reached) in arm A, p = 0.032. Therapy was tolerated well; oral mucositis (p = 0.36) and fatigue (p = 0.08) being more in arm B. QoL assessment revealed modest improvement in ‘symptom scales’ in Arm B. Serum VEGF and PDGF levels decreased with therapy in both arms (Arm A-p < 0.0001, Arm B-p < 0.016). ConclusionAddition of pazopanib to etoposide and cyclophosphamide could be a novel oral combination for metronomic therapy for platinum resistant/refractory EOC. Trial registrationCTRI/2017/10/010219.

Angiogenesis and chemotherapy resistance: optimizing chemotherapy scheduling using mathematical modeling

Chemotherapy remains a widely used cancer treatment. Acquired drug resistance may greatly reduce the efficacy of treatment and means to overcome it are a topic of active discussion among researchers. One of the proposed solutions is to shift the therapeutic paradigm from complete eradication of cancer to maintenance, i.e., to treat it as a chronic disease. A concept of metronomic therapy (low chemotherapy doses applied continuously) emerged in early 2000s and was henceforth shown to offer a number of benefits, including targeting endothelial cells and reducing acquired drug resistance. Using mathematical modeling and optimal control techniques, we investigate the hypothesis that lower doses of chemotherapy are beneficial for patients. Our analysis of a mathematical model of tumor growth under angiogenic signaling proposed by Hahnfeldt et al. adapted to heterogeneous tumors treated by combined anti-angiogenic agent and chemotherapy offers insights into the effects of metronomic therapy. Firstly, assuming constant long-term drug delivery, the model suggests that the longest survival time is achieved for intermediate drug doses. Secondly, by formalizing the notion of the therapeutic target being maintenance rather than eradication, we show that in the short term, optimal chemotherapy scheduling consists mainly of a drug applied at a low dose. In conclusion, we suggest that metronomic therapy is an attractive alternative to maximum tolerated dose therapies to be investigated in experimental settings and clinical trials.

Metronomic Chemotherapy Modulates Clonal Interactions to Prevent Drug Resistance in Non-Small Cell Lung Cancer.

Simple SummaryInside a tumor mass, drug resistant and sensitive cell populations co-exist, leading to a therapeutic challenge in oncology. In this study, we developed 2D and 3D co-culture systems and mathematical modeling to better understand how these different populations impact each other. We demonstrated that drug-sensitive cell populations inhibit the growth of drug-resistant populations. Mathematical modeling predicted that metronomic schedules, using chronic administration of drugs at low doses, could better control intratumor cell dynamics. We validated our in silico data in 3D and in vivo models. Finally, we demonstrated that metabolic cell activity of drug-sensitive cells could play a key role in controlling the proliferation of drug-resistant cells. Altogether, our study reports a new mechanism of action of metronomic therapy and paves the way for using it to better control drug resistance.Despite recent advances in deciphering cancer drug resistance mechanisms, relapse is a widely observed phenomenon in advanced cancers, mainly due to intratumor clonal heterogeneity. How tumor clones progress and impact each other remains elusive. In this study, we developed 2D and 3D non-small cell lung cancer co-culture systems and defined a phenomenological mathematical model to better understand clone dynamics. Our results demonstrated that the drug-sensitive clones inhibit the proliferation of the drug-resistant ones under untreated conditions. Model predictions and their experimental in vitro and in vivo validations indicated that a metronomic schedule leads to a better regulation of tumor cell heterogeneity over time than a maximum-tolerated dose schedule, while achieving control of tumor progression. We finally showed that drug-sensitive and -resistant clones exhibited different metabolic statuses that could be involved in controlling the intratumor heterogeneity dynamics. Our data suggested that the glycolytic activity of drug-sensitive clones could play a major role in inhibiting the drug-resistant clone proliferation. Altogether, these computational and experimental approaches provide foundations for using metronomic therapy to control drug-sensitive and -resistant clone balance and highlight the potential of targeting cell metabolism to manage intratumor heterogeneity.

Abstract PS11-30: Can metronomic maintenance therapy (MMT) after completion of standard therapy help prevent relapses in patients (Pts) with non-metastatic triple-negative breast cancer (TNBC)

Abstract Background: In-spite of the standard neoadjuvant and adjuvant therapies, stage for stage many more patients with TNBC relapse. This may be because of lack of effective maintenance therapy for TNBC Pts. Recently MMT is being explored to improve outcomes in TNBC. We present a retrospective and prospective analysis of consecutive Pts with TNBC treated at BKLWalawalkarHospital, the rural outreach center of Tata Memorial Centre (India), wherein the outcome of TNBC Pts receiving MMT is being compared to historical control group who did not receive the same. Methods: After standard anthracycline or anthracycline+taxane based therapy, TNBC Pts were either observed (Sept 2003 to March 2011) or received MMT (Nov 2008 to Dec 2018).MMT consisted of 2 phases: initial 12 weeks of daily oral celecoxib (200 mg BD) and cyclophosphamide (50 mg OD) along with 12 doses of weekly IV cisplatin (25 mg/m2). This was followed by 1 year of Phase II maintenance consisting of oral daily metformin (500 mg BD), cyclophosphamide (50 mg OD) along with weekly methotrexate (12 mg/m2).When CAF is the standard regimen 2 phases of maintenance was given , after anthracyclines and taxanes were proved as a standard regimen maintenance was restricted to Phase II considering overlapping toxicities like neuropathy. Results: There were 118 evaluable TNBC Pts. 25 Pts did not receive any MMT.Of the 93 remaining Pts initial 25 received both Phase I &amp; II MMT , 1 patient received only phase I and subsequent 61 Pts have received only Phase II MMT. 6 patients progressed while on initial standard therapy and were not evaluable to assess the effect of MMT .Hence 112 patients are analysed further for outcome.STAGE STRATIFICATION : 8 Pts(6.7%) had AJCC Stage I; 48 Pts(40.6%) had AJCC Stage II; &amp; 62 patients(52.5) had AJCC Stage III disease.MMT and observation groups were comparable with respect to baseline characteristics such as age &amp; stage . Out of 112 patients 87 received MMT and 9 events were noted ,25 did not received MMT and 12 events were noted.EFS by March 2020 is 89.7% in MMT group and 52% in non- MMT group . Median EFS in MMT group is 11.3 yrs ( 9.4 yrs-13.14 yrs 95% CI) , in Off MMT group median EFS 9.2 yrs( 6.4-12 yrs 95% CI).Overall comparison was done by Log rank analysis (Significance 0.006).Median overall survival in OMCT group is 11.8yrs ( 9.9yrs-13.8yrs 95% CI), in non MMT group OS is 9.8yrs( 7.1 yrs-12.6yrs) with significance 0.002.61 patients who received Phase II MMT OS is 13.4 yrs ( 12.5yrs-14.4 yrs 95% CI).By stage stratification in non MMT group 2 patients belong to Stage I , 9patients belongs to Stage II and 14 patients belongs to Stage III. TOXICITIES : MTX 25% dose reduction was done in 7 patients due to Grd2 Mucositis, cyclophosphamide alone was stopped in 1 patient due to grade 3 fatigue, MTX and Cyclophosphamide was stopped in 2 patientsdue grade3 anemia and grade 4 neutropenia, blood transfusion was done in them.Toxicities are much less when compared to CREATEX trial and the follow up duration is very long. Conclusion: Most of the TNBC patients relapse in the early period of follow up and there is an unmet need in the improvement of management. If low dose chemotherapy is given for 1 yr there is a significant improvement in EFS and OS without muchdecrease in QOL.l. This strategy is worthy of being evaluated in definitive randomized trials in TNBC women with large numbers. Citation Format: Kripa Bajaj, Shripad Banavali. Can metronomic maintenance therapy (MMT) after completion of standard therapy help prevent relapses in patients (Pts) with non-metastatic triple-negative breast cancer (TNBC) [abstract]. In: Proceedings of the 2020 San Antonio Breast Cancer Virtual Symposium; 2020 Dec 8-11; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2021;81(4 Suppl):Abstract nr PS11-30.

Metronomic Chemotherapy with Cyclophosphamide as a Second Line Treatment in Advanced Hepatocellular Cancer: A Case Report

Purpose: Metronomic chemotherapy is a new modality of drug administration in cancer management. Metronomic chemotherapy entails chronic, equally spaced administration of low doses of various chemotherapeutic drugs without extended rest periods. The use of metronomic therapy as a second-line treatment in advanced hepatocellular cancer (HCC) or metastatic HCC still remains under investigation. We report an unusual case with advanced metastatic HCC, who had an impressive response to metronomic therapy with Cyclophosphamide. Method: A 49-year-old Caucasian female patient diagnosed with a very large (∼14cm) right liver lobe HCC on a background of non-alcoholic fatty liver disease. In July 2016 she underwent initially right hepatic artery transarterial chemoembolization (TACE) and right hepatectomy ten days after TACE. During the follow-up period, she presented early disease recurrence (in 8 months post-liver resection) with lung and peritoneal metastases. A protein kinase inhibitor (Sorafenib) was administered for six months, without response. Afterwards, Cyclophosphamide administration at low doses, as metronomic chemotherapy, provided complete regression of the metastatic lesions. Results: The patient remains in good performance status 4,5 years after the initial diagnosis, without signs of recurrence in her recent follow-up. Conclusion: Using Cyclophosphamide as metronomic chemotherapy in advanced HCC may have an anti-angiogenic antitumor effect. Future clinical trials need to demonstrate this effect in terms of tumour suppression and increased disease-free survival.