Outpatient anti-spike monoclonal antibody administration is associated with decreased morbidity and mortality among patients with cancer and COVID-19 (preprint)

Background: Patients with cancer have many comorbidities that increase their risk of death from Coronavirus disease 2019 (COVID-19). Anti-spike monoclonal antibodies (mAbs) reduce the risk of hospitalization or death from COVID-19 in the general population. To our knowledge, no studies have focused on the clinical efficacy of mAbs compared to no outpatient treatment exclusively among patients with solid tumors and hematologic malignancies, who are often excluded from clinical trials.  Methods: We studied patients with cancer who had COVID-19 between 11.9.2020 and 7.21.2022 and received mAbs in an outpatient setting. We compared hospitalization and mortality rates to those of patients with cancer concurrently diagnosed with COVID-19, who were eligible for mAbs, but did not receive any outpatient treatment. Results: 63 patients received mAbs and 89 no outpatient treatment. Administration of mAbs was associated with lower 90-day hospitalization (20.6% vs. 60.7%, p<0.001), all-cause (6.3% vs. 19.1%, p=0.025) and COVID-19-attributed (3.2% vs. 14.6%, p=0.019) mortality rates, and lower peak O2 requirements (ordinal Odds Ratio [OR]=0.33, 95%Confidence Intervals [CI]=0.20-0.53). Administration of mAbs (aHR 0.21, p<0.001), age (≥ 60 years, adjusted Hazard Ratio [aHR] 1.86, p=0.033), and metastases (aHR 0.41, p=0.007) were independently associated with hospitalization. mAb treatment remained significantly associated with all-cause (aHR 0.27, p=0.019) and COVID-19-attributed (aHR 0.19, p=0.031) mortality, after adjustment for other factors.  Conclusions: mAb administration was associated with improved clinical outcomes among vulnerable patients with cancer and COVID-19. With no mAbs approved currently for treatment against the prevalent circulating variants, the development of new mAbs should be a research priority.

A potential alternative systemic treatment option for epithelioid sarcoma (preprint)

Background: Epithelioid sarcoma is a rare soft tissue sarcoma characterized by SMARCB1/INI1 deficiency. Much attention has been paid to the selective EZH2 inhibitor tazemetostat, where other systemic treatments are generally ignored. To explore alternative treatment options, we studied the effects of irinotecan-based chemotherapy in a series of epithelioid sarcoma patients. Methods: We retrospectively reviewed data from patients with metastatic or unresectable epithelioid sarcoma at the Peking University People’s Hospital treated with irinotecan (50 mg/m2/d d1-5 Q3W) in combination with Anlotinib (12 mg Qd, 2 weeks on and 1 week off) from July 2015 to November 2021. Results: A total of 54 courses were administered. With a median follow up of 21.2 months (95% CI, 12.2, 68.1), the 5-year overall survival rate was 83.3%. Five of eight (62.5%) patients presented with unresectable localized lesions, including local tumor thrombosis and lymphatic metastasis. The other patients had unresectable pulmonary metastases. Six of eight (75%) patients had progressed following two lines of systemic therapy. The objective response rate reached 37.5% (three of eight patients) while stabilized disease was observed in 62.5% (five of eight) of patients. No patient had progressed at initial evaluation. At the last follow up, two patients were still using the combination and three patients had ceased the therapy due to toxicities such as diarrhea, nausea, and emesis. One patient changed to tazemetostat for maintenance and one patient stopped treatment due to coronavirus disease 2019 (COVID-19). Another patient stopped therapy as residual lesions had been radiated. Conclusions: The combination of irinotecan and Anlotinib as a salvage regimen may be considered another effective treatment option for refractory epithelioid sarcoma. Trial registration: This trial was approved in the Medical Ethics Committee of Peking University People’s Hospital on October 28, 2022 (No.: 2022PHD015-002). The trial was registered in Clinicaltrials.gov with identifier no. NCT05656222.

R0 Surgical Resection of Giant Dedifferentiated Retroperitoneal Liposarcomas in the COVID era: Nephrectomy or Not Nephrectomy? (preprint)

Background: Retroperitoneal sarcomas (RPS) are rare findings that can grow into large masses without eliciting severe symptoms. Nowadays surgical resection is the only radical therapy, whenever possible. We present two consecutive cases of RPSs that resulted in dedifferentiated liposarcomas (DDLPS) and underwent R0 surgical resection with and without a nephron-sparing procedure. The diagnostic workup, the surgical approach, the impact of late surgical management due to the COVID pandemic, and the latest literature on the topic will be discussed and analyzed. Case Presentation: The patients, who refused to undergo any medical examination during the prior two years due to the COVID pandemic, were admitted to our Institution complaining about weight loss and general abdominal discomfort. In the first case, we observed a primitive giant abdominal right neoplasm of retroperitoneal origin enveloping and medializing the right kidney. The second patient had a similar primitive retroperitoneal giant left neoplasm which didn’t affect the kidney. Given the masses’ characteristics and the absence of distant metastases, after a multidisciplinary discussion, radical surgical removal was carried out for both patients. The lesions appeared well-defined from the surrounding tissues, and significantly compressed all the adjacent organs, without signs of infiltration. In the first patient, the right kidney was surrounded and undetachable from the tumor and it was removed en bloc with the mass. The second patient benefited from a nephron-sparing resection, thanks to the existence of a clear cleavage plane. The postoperative courses were uneventful. Both the histological examinations were oriented towards a DDLPS. And both patients were addressed with adjuvant chemotherapy. Conclusions: The treatment of giant RPS is still challenging and requires multidisciplinary treatment as well as, when possible, radical surgical removal. The lack of tissue infiltration and the avoidance of major organs’ excision or reconstruction (including the kidney) could lead to an easier postoperative course and a better prognosis. When possible, surgical management of recurrences or incompletely resected masses must be pursued. As the COVID pandemic caused limited medicalization of many population groups and delayed diagnosis of other oncologic diseases, an increased number of DDLPSs could be expected in the near future. 

A phase III, randomized, open-label study (CONTACT-02) of cabozantinib plus atezolizumab versus second novel hormone therapy in patients with metastatic castration-resistant prostate cancer.

Cabozantinib inhibits multiple receptor tyrosine kinases, including the TAM kinase family, and may enhance response to immune checkpoint inhibitors. One cohort of the ongoing phase Ib COSMIC-021 study (NCT03170960) evaluating cabozantinib plus the PD-L1 inhibitor atezolizumab in men with metastatic castration-resistant prostate cancer (mCRPC) that has progressed in soft tissue on/after enzalutamide and/or abiraterone treatment for metastatic disease has shown promising efficacy. Here, we describe the rationale and design of a phase III trial of cabozantinib plus atezolizumab versus a second novel hormone therapy (NHT) in patients who have previously received an NHT for mCRPC, metastatic castration-sensitive PC or nonmetastatic CRPC and have measurable visceral disease and/or extrapelvic adenopathy - a population with a significant unmet need for treatment options. Trial Registration Clinical Trial Registration: NCT04446117 (ClinicalTrials.gov) Registered on 24 June 2020.

Lipid nanoparticle-mediated lymph node-targeting delivery of mRNA cancer vaccine elicits robust CD8+ T cell response.

The targeted delivery of messenger RNA (mRNA) to desired organs remains a great challenge for in vivo applications of mRNA technology. For mRNA vaccines, the targeted delivery to the lymph node (LN) is predicted to reduce side effects and increase the immune response. In this study, we explored an endogenously LN-targeting lipid nanoparticle (LNP) without the modification of any active targeting ligands for developing an mRNA cancer vaccine. The LNP named 113-O12B showed increased and specific expression in the LN compared with LNP formulated with ALC-0315, a synthetic lipid used in the COVID-19 vaccine Comirnaty. The targeted delivery of mRNA to the LN increased the CD8+ T cell response to the encoded full-length ovalbumin (OVA) model antigen. As a result, the protective and therapeutic effect of the OVA-encoding mRNA vaccine on the OVA-antigen-bearing B16F10 melanoma model was also improved. Moreover, 113-O12B encapsulated with TRP-2 peptide (TRP2180-188)-encoding mRNA also exhibited excellent tumor inhibition, with the complete response of 40% in the regular B16F10 tumor model when combined with anti-programmed death-1 (PD-1) therapy, revealing broad application of 113-O12B from protein to peptide antigens. All the treated mice showed long-term immune memory, hindering the occurrence of tumor metastatic nodules in the lung in the rechallenging experiments that followed. The enhanced antitumor efficacy of the LN-targeting LNP system shows great potential as a universal platform for the next generation of mRNA vaccines.

Pattern of breast cancer presentation during the COVID-19 pandemic: results from a cohort study in the UK.

Background: This study aimed to explore the hypothesis that the stage of breast cancer at initial diagnosis in 2020 is more advanced compared with 2019. Methods: Tumor, node, metastasis and Union for International Cancer Control (UICC) stages of new breast cancer diagnoses at the Bucks Breast Unit from May 2019 to October 2020 were reviewed. A p < 0.05 was considered significant. Results: Average UICC stage increased from 1a in 2019 to 2a in 2020 (p < 0.01). Excluding cancers detected through screening, UICC stage still increased from 1b in 2019 to 2a in 2020 (p = 0.0184). There was a significant increase in the percentage of node-positive patients (p = 0.0063) and patients with metastatic disease (p = 0.0295) on initial presentation. Conclusion: Overall, patients presented with higher UICC stages and more node-positive and metastatic disease on initial diagnosis in 2020 compared with 2019.

Plain language summary During the coronavirus disease 2019 pandemic, breast cancer screening services were halted across the UK. Patients were also encouraged to stay home and to seek medical attention only in an emergency. The authors hypothesized that this might have led to delays in presentation to breast cancer clinics or missed cancer diagnoses. While patients are at home with undiagnosed breast cancer, the cancer can grow and spread. The authors evaluated whether these delays in presentation led to patients presenting with more advanced breast cancers when they finally presented to a breast cancer clinic. The authors collected data on breast cancer stages for a patient group in 2020 (during the height of the pandemic) and compared them with a patient group in 2019. The authors' results did indeed show that patients presented, on average, with more advanced breast cancers in 2020 compared with 2019.

Possibility of SARS-CoV-2 infection in metastatic microenvironment of cancer (preprint)

According to a report from the World Health Organization, the mortality and severity rates among patients with cancer infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) are significantly higher than those of individuals infected with SARS-CoV-2 without complications. Common and cancer-specific risk factors may be involved in the mortality and severity rates of coronavirus disease 2019 (COVID-19). Various factors have been determined to contribute to the aggravation of COVID-19 in patients with cancer. However, on the basis of current research, the factors involved in the aggravation of COVID-19 in patients with cancer have not been fully investigated. In the general course of treatment for patients with cancer, the detection of the formation of metastases in other organs is common. Therefore, the present study investigates the association between lung metastatic lesion formation and SARS-CoV-2 infectivity. On the basis of the results obtained, in the pulmonary micrometastatic niche of patients with ovarian cancer, alveolar epithelial stem-like cells adjacent to the ovarian cancer were observed. Moreover, it was revealed that angiotensin-converting enzyme 2, a host-side receptor for SARS-CoV-2, was expressed in alveolar epithelial stem-like cells adjacent to the ovarian cancer in the pulmonary micrometastatic niche. Furthermore, it was also observed that the SARS-CoV-2 spike glycoprotein receptor-binding domain binds to alveolar epithelial stem-like cells. In other words, it was suggested that patients with cancer and pulmonary micrometastases may be more susceptible to SARS-CoV-2. The prevention of de novo niche formation in metastatic disease may be a new strategy for the clinical treatment of COVID-19 for patients with cancer.

Management of Early Breast Cancer at an Australian NSW Cancer Centre During the Early Phase of COVID-19 Pandemic (preprint)

Background: This study aimed to prospectively record changes to treatment for early breast cancer patients during the first wave of the COVID-19 pandemic in Australia. The purpose was to assess the impact on breast cancer outcomes and to determine the need for any mitigative actions. Methods: The study was conducted in the breast cancer unit of a tertiary referral hospital. Consecutive patients with invasive cancer or ductal cancer in situ (DCIS) discussed in multidisciplinary team (MDT) meetings three times a week between March and June 2020 were included. Patients were newly diagnosed, post-operative or post-neoadjuvant chemotherapy. Standard treatment was defined by Westmead Breast Cancer Institute protocols and any variations related to the pandemic were recorded. Results:145 patients were included (median age 59 years). Pandemic related changes to management were noted in 13 of 145 (9·0%) patients discussed in the MDT meeting. Four patients experienced a delay to cancer treatments, four were not offered reconstructive/symmetrisation surgical procedures, three had altered radiotherapy protocols and two patients were not offered enrolment to a clinical trial. These impacts affected the groups presenting with new cancers (n=7/86, 8·1%), post-operative cases (n=4/25, 16·0%) and post-neoadjuvant chemotherapy cases presenting for surgical planning (n=2/34, 5·9%). Conclusion: Most patients (91·0%) received standard treatment during the first wave of the pandemic. Variations from institutional protocols are not expected to affect local control or survival in this patient cohort and no mitigative actions have been implemented. Quality of life may have been affected for four patients who had downgraded or delayed reconstructive procedures. Institutional strategies such as utilising telemedicine and COVID-free facilities were successfully implemented within the study period.Trial Registration: The study was registered with the Australian New Zealand Clinical Trials Registry(ACTRN12620000869976).Funding Statement: None.Declaration of Interests: RH has participated in advisory boards for AstraZeneca, Bristol Myers Squibb, Eli Lilly, Merck, Merck Sharp and Dohme, Novartis, Oncosec, Pfizer, Roche and Seagen; and has received speaker honoraria from Merck Sharp and Dohme, Novartis and Roche. EE has participated in advisory board for Merck Sharp and Dohme. There are no conflicts of interests to declare for the other authors.Ethics Approval Statement: Approval was obtained from the Sydney West Human Research EthicsCommittee (Project ID 2020/PID00900).

COVID-19 lung injury as a primer for immune checkpoint inhibitors (ICIs)-related pneumonia in a patient affected by squamous head and neck carcinoma treated with PD-L1 blockade: a case report.

By the beginning of the global pandemic, SARS-CoV-2 infection has dramatically impacted on oncology daily practice. In the current oncological landscape, where immunotherapy has revolutionized the treatment of several malignancies, distinguishing between COVID-19 and immune-mediated pneumonitis can be hard because of shared clinical, radiological and pathological features. Indeed, their common mechanism of aberrant inflammation could lead to a mutual and amplifying interaction.We describe the case of a 65-year-old patient affected by metastatic squamous head and neck cancer and candidate to an experimental therapy including an anti-PD-L1 agent. COVID-19 ground-glass opacities under resolution were an incidental finding during screening procedures and worsened after starting immunotherapy. The diagnostic work-up was consistent with ICIs-related pneumonia and it is conceivable that lung injury by SARS-CoV-2 has acted as an inflammatory primer for the development of the immune-related adverse event.Patients recovered from COVID-19 starting ICIs could be at greater risk of recall immune-mediated pneumonitis. Nasopharyngeal swab and chest CT scan are recommended before starting immunotherapy. The awareness of the phenomenon could allow an easier interpretation of radiological changes under treatment and a faster diagnostic work-up to resume ICIs. In the presence of clinical benefit, for asymptomatic ICIs-related pneumonia a watchful-waiting approach and immunotherapy prosecution are suggested.

Development of a Model to Estimate the Association Between Delay in Cancer Treatment and Local Tumor Control and Risk of Metastases.

Importance: The coronavirus disease 2019 (COVID-19) pandemic has led to treatment delays for many patients with cancer. While published guidelines provide suggestions on which cases are appropriate for treatment delay, there are no good quantitative estimates on the association of delays with tumor control or risk of new metastases. Objectives: To develop a simplified mathematical model of tumor growth, control, and new metastases for cancers with varying doubling times and metastatic potential and to estimate tumor control probability (TCP) and metastases risk as a function of treatment delay interval. Design, Setting, and Participants: This decision analytical model describes a quantitative model for 3 tumors (ie, head and neck, colorectal, and non-small cell lung cancers). Using accepted ranges of tumor doubling times and metastatic development from the clinical literature from 2001 to 2020, estimates of tumor growth, TCP, and new metastases were analyzed for various treatment delay intervals. Main Outcomes and Measures: Risk estimates for potential decreases in local TCP and increases in new metastases with each interval of treatment delay. Results: For fast-growing head and neck tumors with a 2-month treatment delay, there was an estimated 4.8% (95% CI, 3.4%-6.4%) increase in local tumor control risk and a 0.49% (0.47%-0.51%) increase in new distal metastases risk. A 6-month delay was associated with an estimated 21.3% (13.4-30.4) increase in local tumor control risk and a 6.0% (5.2-6.8) increase in distal metastases risk. For intermediate-growing colorectal tumors, there was a 2.1% (0.7%-3.5%) increase in local tumor control risk and a 2.7% (2.6%-2.8%) increase in distal metastases risk at 2 months and a 7.6% (2.2%-14.2%) increase in local tumor control risk and a 24.7% (21.9%-27.8%) increase in distal metastases risk at 6 months. For slower-growing lung tumors, there was a 1.2% (0.0%-2.8%) increase in local tumor control risk and a 0.19% (0.18%-0.20%) increase in distal metastases risk at 2 months, and a 4.3% (0.0%-10.6%) increase in local tumor control risk and a 1.9% (1.6%-2.2%) increase in distal metastases risk at 6 months. Conclusions and Relevance: This study proposed a model to quantify the association of treatment delays with local tumor control and risk of new metastases. The detrimental associations were greatest for tumors with faster rates of proliferation and metastasis. The associations were smaller, but still substantial, for slower-growing tumors.

Impact of Covid-19 pandemic for patient care in an Interventional Radiology Unit (preprint)

Purpose: Assess the impact of Covid-19 pandemic in work volume in an Interventional Radiology Unit during the “State of Emergency” (16th March - 30th April) in 2020 and to analyse the short-term consequences for oncology patients.Materials and Methods: Single-centre retrospective analysis. The number and type of procedures performed during the “State of Emergency” was compared with the homologous period in 2019. The second analysis compared the impact on disease progression for oncology patients after the “State of Emergency”. All patients that had a scheduled loco-regional treatment (LRT) (74 hepatocellular carcinoma (HCC); 10 liver metastases) between 2nd May - 16th July 2020 were compared with the homologous period in 2019 (68 HCC; 11 liver metastases). The compared outcome measures included: baseline data, time from diagnostic imaging to LRT, LRT performed as planned, change in LRT.Results: There was a 55.2% reduction of procedures during the “State of Emergency” (n=77 in 2020; n=172 in 2019) with a significant increase in urgent procedures (48.1% in 2020; 33.1% in 2019; p=0.0120). Post-“State of Emergency”, in 2020, HCC patients had higher model of end-stage liver disease (MELD) scores (p=0.0124) and larger tumours (mean difference of 8.7 mm, p=0.0071). Mean time from diagnostic imaging to LRT increased 14.1 days (p=0.0439). More patients received different or no LRT due to disease progression (15.5% in 2020; 3.8% in 2019; p=0.0061).Conclusion: There was a reduction in interventional oncology treatments during the “State of Emergency” with more patients experiencing disease progression precluding LRTs in the following months. 

Course of Sars-CoV2 Infection in Patients with Cancer Treated with anti-PD-1: A Case Presentation and Review of the Literature.

The outbreak of COVID-19 pandemia is a major health worldwide concern. Patients with cancer might have a worse outcome, because of the immunosuppression determined by the tumor itself and anti-cancer treatments, including chemotherapy and radiotherapy. The impact and course of viral infection in patients receiving immunotherapy remains unknown. We report the case of a patient with metastatic melanoma, long responder to anti PD-1 blockade who got infected with Sars CoV-2, recovering without sequelae. A critical review of literature was performed. Limited data available in literature support the possibility to continue the immunotherapy in patients with cancer under control.

Exploring metastatic breast cancer treatment changes during COVID-19 pandemic.

The emergency caused by COVID-19 pandemic has imposed a sudden reorganization of the healthcare structures and has created consequences in cancer patients management. General clinical recommendations for cancer patients were released, even if limited clinical cancer-specific data were available. A number of critical issues have come out during COVID-19 pandemic in the management of patients with metastatic breast cancer (MBC). To explore the changes in the treatment of patients with MBC during COVID-19 pandemic, we promoted a survey to the oncologists operating in the Italian breast units. The results of this survey show that Italian oncologists have tried to ensure continuity of care for patients with MBC. De-escalation of cancer treatments, especially monotherapy administration, and greater use of oral anticancer drugs are the main changes that emerge from this survey. Some subgroups of patients, especially the elderly and endocrine-responsive patients, have been undertreated during the COVID-19 pandemic.

Type I Interferon Limits Viral Dissemination-Driven Clinical Heterogeneity in a Native Murine Betacoronavirus Model of COVID-19 (preprint)

Emerging clinical data demonstrates that COVID-19, the disease caused by SARS-CoV2, is a syndrome that variably affects nearly every organ system. Indeed, the clinical heterogeneity of COVID-19 ranges from relatively asymptomatic to severe disease with death resultant from multiple constellations of organ failures. In addition to genetics and host characteristics, it is likely that viral dissemination is a key determinant of disease manifestation. Given the complexity of disease expression, one major limitation in current animal models is the ability to capture this clinical heterogeneity due to technical limitations related to murinizing SARS-CoV2 or humanizing mice to render susceptible to infection. Here we describe a murine model of COVID-19 using respiratory infection with the native mouse betacoronavirus MHV-A59. We find that whereas high viral inoculums uniformly led to hypoxemic respiratory failure and death, lethal dose 50% (LD50) inoculums led to a recapitulation of most hallmark clinical features of COVID-19, including lymphocytopenias, heart and liver damage, and autonomic dysfunction. We find that extrapulmonary manifestations are due to viral metastasis and identify a critical role for type-I but not type-III interferons in preventing systemic viral dissemination. Early, but not late treatment with intrapulmonary type-I interferon, as well as convalescent serum, provided significant protection from lethality by limiting viral dissemination. We thus establish a Biosafety Level II model that may be a useful addition to the current pre-clinical animal models of COVID-19 for understanding disease pathogenesis and facilitating therapeutic development for human translation.

Management of COVID-19 in Liver Transplant Recipients with Immunosuppressant Therapy: Experiences of an Iranian Transplant Registry (preprint)

Background: Following the pandemic of COVID-19 and the increased COVID-19 risk in transplant patient receptions, the authors assessed the prevalence, clinical course, and the outcome of the COVID-19 infection among liver transplant receptions. Methods: By designing and the use of researcher made questionnaire and the use of medical services, liver transplantation recipients under our center surveyed in terms of COVID-19 infection.Results: Seven patients infected with COVID-19 were identified from 265 liver transplantation recipients. The majority of patients were male and had COVID-19 despite being in-home quarantine. All patients received immunosuppressive drugs during infection with COVID-19 with no change in the routine immunosuppressive therapy. Among the identified patients, 5 recovered and 2 died. One of the dead patients, in addition to having a liver transplant, suffered brain cancer with metastasis to the lungs. Conclusion: It seems that the in liver transplants infected with COVID-19, the immunosuppressive drugs causes mild to moderate illness, and even recover from the disease.However, more evidence is needed to prove this hypothesis. It is also recommended that transplant recipients should be warned about personal hygiene and closely be monitored by organ transplant centers. 

Innovative countermeasures can maintain cancer care continuity during the coronavirus disease-2019 pandemic in Korea.

BACKGROUND: Even though Korea was known to have the highest number of coronavirus disease-2019 (COVID-19) infection in the early phase of the pandemic, Korea was able to successfully flatten the curve in a short period of time without extreme measures. We compared the status of cancer management before and after COVID-19 and analysed how cancer care continuity was maintained in Korea. PATIENTS AND METHODS: We investigated the medical records on the number of cancer diagnosis, cancer surgery, radiation therapy and scheduled chemotherapy conducted in Korea University Anam Hospital from January 1 to April 30, 2019 and from the same period in 2020. We also collected the data of metastatic cancer patients who were hospitalised due to respiratory disease. RESULTS: Of all diagnoses, 1694 cancer diagnoses were made in the study period of 2019, and 1445 diagnoses in 2020 (decreased by 14.7%); the cancer surgery performed 830 and 800 cases; the set-up for radiation therapy decreased from 185 to 140 cases; the number of systemic chemotherapies for metastatic cancer patients treated in department of medical oncology increased from 2555 to 2878 cases. Among hospitalised patients, emergency centre visit, intensive care unit admission, discharge after recovery and death reveal no drastic changes. CONCLUSIONS: Routine cancer care for patients with metastatic cancer has been maintained without significant difference before and after the COVID-19 pandemic. The Korean government's innovative countermeasures in the early phase of outbreak made it possible for cancer care practitioners to provide cancer patients with regular care under the standard infection control protocol.

Metronomic chemotherapy for patients with metastatic breast cancer: Review of effectiveness and potential use during pandemics.

Metronomic chemotherapy (M-CT) is defined as dose dense administration of chemotherapy at lower doses than maximum tolerated dose but at shorter free intervals, to obtain a near continuous exposure of cancer cells to those potentially effective drugs. M-CT is a useful strategy to obtain response, overcome resistance and reduce side effects, with low costs. This review will focus on the use of M-CT in advanced breast cancer (ABC). Cytostatic and cytotoxic effect on cancer cells, the anti-angiogenic and the immunomodulatory effects are its main mechanisms of actions. Many clinical trials proved the efficacy and tolerability of different monotherapies and combinations of chemotherapeutic agents administered in metronomic doses and frequencies in ABC. M-CT is a reasonable option for second and later lines of chemotherapy in metastatic breast cancer including those with prior anthracycline or taxane exposure, older patients and patients with comorbidities, and even as first-line in certain groups of patients. The acceptable efficacy and low toxicity of oral metronomic chemotherapy makes it a reasonable option during COVID-19 pandemic as well as in the post-COVID era which is projected to last for some time.