Oral Etoposide Research Articles

1318P - Carboplatin (CB) combined with oral or intravenous (IV) etoposide (ET) for advanced extra-pulmonary (EP) poorly differentiated (PD) neuroendocrine carcinoma (NEC): Real-world findings from two European neuroendocrine tumour society centres of excellence

1318P - Carboplatin (CB) combined with oral or intravenous (IV) etoposide (ET) for advanced extra-pulmonary (EP) poorly differentiated (PD) neuroendocrine carcinoma (NEC): Real-world findings from two European neuroendocrine tumour society centres of excellence

Benefits of Etoposide Maintenance Therapy for Patients With Extensive SCLC Who Experienced PR/CR/SD After 4-6 Cycles of First-Line Chemotherapy With Etoposide Plus Cisplatin/Carboplatin

Background: The clinical remission period of small cell lung cancer was shorter after the first-line treatment. Aim: To observe whether oral etoposide maintenance therapy can improve the progression-free survival (PFS) in patients with lung cancer who experienced complete remission (CR), partial remission (PR), and disease stabilization (SD) after 4-6 cycles of first-line chemotherapy with etoposide plus cisplatin/carboplatin. Methods: A retrospective analysis was performed on patients with ED-SCLC who were treated with etoposide (100 mg/d, iv.gtt days 1-5 with a cycle length of every 21 days) plus 4-6 cycles of cisplatin/carboplatin chemotherapy during the period from 1 January 2014 to 31 December 2016 at the Cancer Hospital affiliated with Zhengzhou University. All the patients were divided into 2 groups based on the criteria whether they had gone through maintenance therapy with etoposide: nonmaintained treatment group (NT), and maintenance treatment group (TH). The maintenance treatment group was further subdivided into the 25 mg subgroup (group A) and the 50 mg subgroup (group B) according to the maintenance dose. Analysis of 1-year progression-free survival (PFS) was conducted using the Kaplan-Meier method and Cox proportional hazards model. PFS1 was defined as the first day of first-line treatment until the disease progressed or the last follow-up time. PFS2 was defined as the first day of etoposide capsule treatment until disease progression or the last follow-up time. Results: A total of 85 patients were enrolled in this study; there were 50 patients in the NT group (58.8%) and 35 patients in the TH group (41.2%). In the TH group, there were 10 (28.6%) in the 25 mg subgroup (group A) and 25 (71.4%) in the 50 mg subgroup (group B). Detailed patient information and tumor-related parameters are shown in Table 1. For all patients, the median PFS1 in the first-line regimen with either the cisplatin or carboplatin group was 6.5 months (95% CI: 5.870-7.130) and 6.4 months (95% CI: 5.970-6.970) respectively ( P = 0.0551). Median progression-free survival for all patients and the median PFS for patients of the TH group were 6.5 months (95% CI: 6.138-6.861) and 7.2 months (95% CI: 6.702-7.698) respectively; the median PFS for the NT group, subgroup A, and subgroup B were 5.7 months (95% CI: 4.862-6.478), 6.7 months (95% CI: 6.390-7.010), and 7.4 months (95% CI: 6.386-8.474), respectively ( P = 0.0043). Median PFS2 was 2.400 months for maintenance treatment patients; the median PFS2 in the 25 mg and 50 mg groups was 2.100 months (95% CI 1.690-2.510 months) and 3.030 months (95% CI 1.937-4.123 months), respectively ( P = 0.0309). Conclusion: Use of etoposide capsules to maintain chemotherapy can significantly prolong the progression-free survival (PFS) of CR, PR, and SD in patients with extensive SCLC and improve 1-year survival; a 50-mg dose is better than 25 mg.

Abstract CT004: Front-line therapy of DIPG using the IDO pathway inhibitor indoximod in combination with radiation and chemotherapy

Abstract BACKGROUND: In theory, combining immunotherapy with radiation (RT) and chemotherapy is an appealing therapeutic strategy that may offer potential synergistic benefits. The indoleamine 2,3-dioxygenase (IDO) pathway regulates inflammation and immune responses to apoptotic cells. Indoximod reverses the profound immunosuppression created by IDO in the tumor microenvironment. METHODS: 29 pediatric patients with recurrent or progressive malignant brain tumors were treated in two separate indoximod dose-escalation cohorts. Patients eligible for re-irradiation (re-RT) (17/29) were treated with conformal RT (15-54 Gy) in combination with indoximod, followed by indoximod with cyclic temozolomide (200 mg/m2/day for the first 5 days of each 28-day cycle). Patients not eligible for RT received indoximod plus cyclic temozolomide. After initial response or disease stabilization (at least 4 months), patients who showed progression were offered planned re-RT to escape lesions, surgical debulking where indicated, and cross-over to an alternative chemotherapy regimen (oral metronomic cyclophosphamide plus etoposide) while continuing indoximod immunotherapy. Time to Regimen Failure (TTRF) was used to capture time on study. RESULTS: In aggregate, 29 relapsed patients had a median PFS of 6.2 months, median time on study (TTRF) was 11.7 months, and 9/29 are continuing treatment. Patients given RT had median TTRF 13.5 months vs. 4.3 months for no RT. Patients not eligible for conventional full-dose re-RT (>50 Gy) received lower-dose RT (=<30 Gy) not attempting to target all disease where that would be toxic. 9 of 17 patients received lower-dose, restricted-field RT and median TTRF was 16 months versus 13 months for full-dose RT. Based on these results, a cohort of newly-diagnosed patients with diffuse intrinsic pontine glioma (DIPG) was opened using indoximod during front-line RT (54 Gy) followed by maintenance indoximod plus temozolomide. To date 6 newly-diagnosed DIPG patients have enrolled, all with bulbar signs and bulky disease on MRI at study entry. The first 3 newly-diagnosed DIPG patients have completed induction radio-immunotherapy which was well tolerated with symptomatic improvement in all patients, radiographic responses in 3/3, and near resolution of one tumor at the end of radiotherapy. An additional patient with progressive DIPG received re-RT (27 Gy) combined with indoximod, which was tolerated well with symptomatic improvement and objective tumor reduction on post-RT MRI. CONCLUSIONS: Indoximod was well-tolerated in combination with RT and chemotherapy. TTRF compares favorably with historical controls. Lower-dose, restricted-field RT may be beneficial when combined with indoximod in relapse cases. Front-line studies have begun in a cohort of DIPG patients. Citation Format: Theodore S. Johnson, Dolly Aguilera, Ahmad Al-Basheer, Robert C. Castellino, Bree R. Eaton, Natia Esiashvili, Nicholas Foreman, Ian M. Heger, Eugene P. Kennedy, Charles J. Link, William Martin, Eric K. Ring, Ramses F. Sadek, Amy Smith, Vahanian N. Vahanian, Tobey J. MacDonald, David H. Munn. Front-line therapy of DIPG using the IDO pathway inhibitor indoximod in combination with radiation and chemotherapy [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr CT004.

Apatinib, a novel VEGFR inhibitor, combined with oral etoposide in patients with platinum-resistant or platinum-refractory ovarian cancer: A single-arm, open-label, phase 2 study.

5515Background: Anti-angiogenic therapy combined with chemotherapy could improve the outcome of platinum-resistant ovarian cancer. Apatinib is an oral tyrosine kinase inhibitor which selectively in...

Final results of RENO study: Randomized phase II of oral vinorelbine or etoposide with cisplatin and chemo-radiation in stage III NSCLC. SLCG 10/02.

e20521Background: This study aims to compare efficacy and safety of two widely used combinations of cisplatin (P) in this setting: as etoposide (E) and vinorelbine. This last, in its oral formulati...

Treating Langerhans cell histiocytosis, globally.

Treating Langerhans cell histiocytosis, globally.

Chemotherapy is of Value in Second Line and Beyond, Relapsed High-grade, Serous Epithelial Ovarian Cancer

Epithelial ovarian cancer is chemotherapy responsive, and multiple lines of chemotherapy are often given. However, there are few data with regard to its effectiveness in later lines. Our aim was to assess its benefit in the high-grade, serous subtype relative to the line of therapy, using etoposide as the example. Women treated with oral etoposide at the British Columbia Cancer Agency upon recurrence/progression in the years 2000 to 2010 were reviewed. Kaplan-Meier and Cox regression methods were used to correlate line of therapy with overall survival, progression-free survival, and interval between etoposide initiation and next progression or death (EPFS). A total of 219 women, median age 61, received etoposide as second (17%), third (30%), fourth (26%), fifth (17%), and sixth to eighth (11%) lines of therapy. The median number of cycles was 2 to 4. Patients who received etoposide as fourth-line to eighth-line treatment had a significantly longer median overall survival and initial progression-free survival (from diagnosis to first relapse) when compared with those who received it as second-line to third-line treatment (47.8 vs. 25.8 mo, P<0.0001; and 16.1 vs. 12.1 mo, P<0.0001, respectively); that is, a selected population of survivors received it later in the course of their disease. On univariate analysis, there was no significant difference in median EPFS (range, 2 to 2.9 mo) on the basis of line of therapy. On multivariate analysis, the hazard ratios improved through the third, fourth, and fifth lines (hazard ratios: 0.82, 0.77, and 0.34, respectively), and was statistically significant in the fifth line. The a priori-defined endpoint of clinical benefit was the "percentage not progressing at 3 months," and this was achieved in 32% to 48%. In this retrospective study, a similar degree of benefit from etoposide, as defined by the percentage remaining progression free at 3 months, was seen in all lines of therapy.

Treatment of Langerhans cell histiocytosis with a modified risk-adapted protocol-experience from a tertiary cancer institute in India.

Involvement of risk-organs (RO+) in Langerhans cell histiocytosis (LCH) and inadequate early response identifies patients at high risk for relapse and mortality requiring intensive salvage therapy including stem cell transplant, adding cost and toxicity. To mitigate this, we used a standard induction, augmented with metronomic etoposide, and prolonged maintenance-similarly augmented for RO+, and retrospectively analyzed its impact. LCH patients from 2009 through 2014 were included. Patients received standard vinblastine and prednisolone therapy weekly till week 25 for RO+. Single site (SS) and multisystem (MS) without risk organ involvement (RO-) received 3-weekly pulses from week 13 till week 25. Maintenance was 3-weekly vinblastine and 5-day prednisolone pulses, daily 6-mercaptopurine (60mg/m2 ) and weekly methotrexate (15mg/m2 ) for 18 and 9 months for RO+ and MSRO-, respectively. RO+ also received oral etoposide (50mg/m2 ) for 21 of every 28-day cycle for the first year. Fifty consecutive patients were analyzed. Median age was 36 months (4-189 months). SS, MSRO-, and RO+ were 29 (58%), 12 (24%), and nine (18%), respectively. Four were lost to follow-up and excluded from further evaluation. On response evaluation at week 6, 24 (52%) had no active disease (NAD), 17 (37%) had AD-better (where AD is active disease), and one (2%) had AD-worse. In RO+, eight (66.6%) had AD-better and three (25%) had NAD. Forty-five patients had NAD by week 12. Three patients relapsed. With median follow-up of 39 months (8-84), 5-year event free survival was 85.6% (RO- and SS), and 100% for RO+. One patient's death in remission from unrelated causes resulted in overall survival of 97%. RO+LCH receiving oral etoposide augmented induction and maintenance had early and durable responses. Prolonging maintenance lowered reactivation rates in RO+ and RO-LCH, resulting in excellent survival.

Intravenous versus oral etoposide: efficacy and correlation to clinical outcome in patients with high-grade metastatic gastroenteropancreatic neuroendocrine neoplasms (WHO G3)

High-grade gastroenteropancreatic neuroendocrine neoplasms (GEP-NENs, G3) are aggressive cancers of the digestive system with poor prognosis and survival. Platinum-based chemotherapy (cisplatin/carboplatin + etoposide) is considered the first-line palliative treatment. Etoposide is frequently administered intravenously; however, oral etoposide may be used as an alternative. Concerns for oral etoposide include decreased bioavailability, inter- and intra-patient variability and patient compliance. We aimed to evaluate possible differences in progression-free survival (PFS) and overall survival (OS) in patients treated with oral etoposide compared to etoposide given as infusion. Patients (n = 236) from the Nordic NEC study were divided into three groups receiving etoposide as a long infusion (24 h, n = 170), short infusion (≤ 5 h, n = 33) or oral etoposide (n = 33) according to hospital tradition. PFS and OS were analyzed with Kaplan–Meier (log-rank), cox proportional hazard ratios and confidence intervals. No statistical differences were observed in PFS or OS when comparing patients receiving long infusion (median PFS 3.8 months, median OS 14.5 months), short infusion (PFS 5.6 months, OS 11.0 months) or oral etoposide (PFS 5.4 months, OS 11.3 months). We observed equal efficacy for the three administration routes suggesting oral etoposide may be safe and efficient in treating high-grade GEP-NEN, G3 patients scheduled for cisplatin/carboplatin + etoposide therapy.

An Outpatient, Dose-Intense, Intravenous Cisplatin and Oral Etoposide Regimen for the Treatment of Advanced, Platinum-Resistant Ovarian Cancer.

Advanced-stage, platinum-resistant, ovarian cancer can be treated with dose-intense chemotherapy; one such regimen includes intravenous cisplatin and oral etoposide. To minimize the toxicity associated with weekly cisplatin, pretreatment and posttreatment hydration is required, often necessitating inpatient, overnight admission. We report a shorter, within-day regimen for delivering weekly cisplatin. This was a retrospective study to assess the use of standard (inpatient; treatment time of 12 hours) versus modified (outpatient; treatment time of 4 hours) regimens. The primary outcome included all-grade and grade 3/4 adverse events. Secondary outcomes included clinical benefit response and, median progression-free survival and overall survival. Between January 2012 and December 2014, 66 women with metastatic ovarian cancer received dose-intense weekly cisplatin and oral etoposide (n = 45 standard, n = 21 modified). The commonest all-grade adverse events were anemia (96% vs 90%, standard and modified, respectively), fatigue (73% vs 67%), neutropenia (71% vs 76%), hypocalcemia (51% vs 43%), and thrombocytopenia (49% vs 57%). There were no statistically significant differences in the incidence or grades of adverse events. The clinical benefit response was 53% in the standard group and 62% in the modified group (P = 0.9). The median progression-free survival was 4.2 and 6.5 months (incidence rate ratio, 1.22; 95% confidence interval, 0.71-2.15; P = 0.29), and median overall survival was 6.6 and 8.4 months (incidence rate ratio, 1.83; 95% confidence interval, 1.04-3.35; P = 0.03), in favor of the modified regimen. Our shorter, within-day regimen for delivering dose-intense weekly cisplatin and oral etoposide to treat platinum-resistant metastatic ovarian cancer is safe and efficacious.

Abstract P6-14-06: Oral etoposide (VP-16) in heavily pre-treated metastatic breast cancer: A multicenter national observational study

Abstract Background 20-30% of breast cancer (BC) patients will develop distant metastases. Despite important improvement achieved in the management of metastatic BC (MBC), median overall survival (OS) still ranges from 14 to 50 months, depending on tumor subtypes. Patients often receive many successive lines of therapy over the course of their disease. Few data on efficacy of 3rd and subsequent lines of chemotherapy are available. Although oral etoposide has been used for years in heavily pre-treated MBC patients, real-life data supporting its efficacy are lacking. Methods The primary objective was to assess progression free survival (PFS) in MBC patients having started oral etoposide as 3rd line chemotherapy or more, using the French Epidemiological Strategy and Medical Economics (ESME) database, established in 2014 by Unicancer. Secondary objectives were overall survival (OS) and descriptive and prognostic analyses. Results Of 16703 MBC patients included in the ESME program and covering the 2008-2014 period, 323 received at least 14 days of oral etoposide. Amongst them, 5 were men, 46 received etoposide as 1st or 2nd line chemotherapy, and 7 had no information available regarding line of treatment, leaving 265 for analysis. All received oral etoposide, 255 as monotherapy while 10 pts combined with trastuzumab for HER2+ MBC. Patients' and tumour characteristics are shown in table 1. The mean line of chemotherapy with oral etoposide was 5 (range 3-12). With a median follow-up of 32.2 months [CI95%: 22.0-42.1], median PFS and OS (from initiation of oral etoposide) were 3.1 months [95% CI 2.8-3.7] and 7.4 months [95% CI 6.0-9.9], respectively. No predictive factor for PFS could be identified (age at MBC diagnosis, BC subtype, number of metastatic sites, presence of visceral metastases, disease-free interval, line of treatment). Only a trend for longer PFS was seen in patients &amp;gt; 50 years old, with longer disease-free interval and receiving etoposide earlier. Triple-negative MBC had shorter OS compared to other subtypes (p=0.03). Of note, OS was stable around 7 months for subsequent lines following a 3rd line of chemotherapy. n%Age at MBC diagnosis&amp;lt; 50 yo8331.3≥ 50 yo18268.7Primary BC subtypeER+ HER2-16662.6HER2+3814.3Triple negative5621.1ND51.9Number of metastatic sites115458.1≥ 211141.9Visceral metastasisNo13249.8Yes13350.2Disease-free intervalde novo4015.16-24 months4115.524-60 months7427.9&amp;gt; 60 months11041.5Chemotherapy line36323.846524.554717.764316.3≥ 74717.7 Conclusions Oral etoposide may achieve significant disease control in heavily pre-treated MBC, with a 3.1-month median PFS and independently from prognostic factors. Moreover, etoposide has the major advantage of an oral drug administered at home with a low cost. A case-control study is ongoing. Citation Format: Lerebours F, Carton M, Bacrie J, Pierga J-Y, Rouzier R, Saghatchian M, Dalenc F, Mailliez A, Levy C, Firmin N, Debled M, Leheurteur M, Desmoulins I, Lefeuvre C, Goncalves A, Uwer L, Ferrero J-M, Eymard J-C, Petit T, Mouret-Reynier M-A, Piot I, Perrocheau G, Caillot C, Perol D. Oral etoposide (VP-16) in heavily pre-treated metastatic breast cancer: A multicenter national observational study [abstract]. In: Proceedings of the 2017 San Antonio Breast Cancer Symposium; 2017 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2018;78(4 Suppl):Abstract nr P6-14-06.

Oral etoposide in heavily pre-treated metastatic breast cancer: A retrospective series

BackgroundPatients with metastatic breast cancer (MBC) can derive clinical benefit from several subsequent lines of chemotherapy. However, in heavily pre-treated patients, agents with clinical activity, a favourable side effects profile and a convenient administration modality are preferred. Patients and MethodsWe retrospectively analyzed 110 patients with previously treated MBC, who received oral etoposide at the dose of 50 mg/day for 20 days in 28 days cycles, between 2003 and 2017. Because this was not a prospectively planned study, to describe the clinical performance of oral etoposide we adopted the approach suggested by Dzimitrowicz and colleagues (J Clin Oncol. 2016; 34:3511–17); Tumour Response (TR) was defined as the proportion of physician-reported clinical or imaging response; Prolonged Duration on Therapy (PDT) as the proportion of non-progressing patients whose treatment lasted more than 6 months. Furthermore, we evaluated median duration on therapy (TD) and median Overall Survival (OS) by the Kaplan Meier method. ResultsThe median number of previous chemotherapy lines was 5 (range 2–8). TR, PDT, median TD and median OS were 6.4%, 18.2% 4 (range 3.5–4.5) and 10.6 (range 8.4–12.8) months respectively. Interestingly, etoposide activity was unrelated to the number of previous lines and type of metastatic involvement. Oral etoposide was well tolerated with only two patients discontinuing therapy due to toxicity. ConclusionsIn this large, single Institution, real practice analysis oral etoposide is a valuable and safe option for pre-treated metastatic breast cancer patients and might be considered in patients failing other approaches, but still suitable for chemotherapy.

Etoposide and temozolomide in combination for the treatment of progressive small-cell lung cancer central nervous system metastases: two cases.

Progression of central nervous system (CNS) metastases from small cell lung cancer (SCLC) after radiation therapy is associated with a poor prognosis. We present two cases of patients with progressive CNS metastases from SCLC treated with oral temozolomide and etoposide. Sustained clinical responses and radiographic stability were demonstrated. The palliative chemotherapy regimen was well tolerated. A regimen of oral temozolomide and etoposide for progressive CNS metastases from SCLC is well tolerated and may be associated with sustained stability of disease.

As-Needed Vs Immediate Etoposide Chemotherapy in Combination With Antiretroviral Therapy for Mild-to-Moderate AIDS-Associated Kaposi Sarcoma in Resource-Limited Settings: A5264/AMC-067 Randomized Clinical Trial.

Mild-to-moderate AIDS-associated Kaposi sarcoma (KS) often responds to antiretroviral therapy (ART) alone; the role of chemotherapy is unclear. We assessed the impact of immediate vs as-needed oral etoposide (ET) among human immunodeficiency virus (HIV)-infected individuals with mild-to-moderate KS initiating ART. Chemotherapy-naive, HIV type 1-infected adults with mild-to-moderate KS initiating ART in Africa and South America were randomized to ART (tenofovir/emtricitabine/efavirenz) alone (chemotherapy "as-needed" arm) vs ART plus up to 8 cycles of oral ET (immediate arm). Participants with KS progression on ART alone received ET as part of the as-needed strategy. Primary outcome was ordinal as follows: failure, stable, and response at 48 weeks. Secondary outcomes included time to initial KS progression, KS-associated immune reconstitution inflammatory syndrome (KS-IRIS), and KS response. Of 190 randomized participants (as-needed = 94, immediate = 96), the majority were men (71%) and African (93%). Failure (53.8% vs 56.6%), stable (16.3% vs 10.8%), and response (30% vs 32.5%) did not differ between arms (as-needed vs immediate) among those with week 48 data potential (N = 163, P = .91). Time to KS progression (P = .021), KS-IRIS (P = .003), and KS response (P = .003) favored the immediate arm. Twenty-five participants died (13%). Mortality, adverse events, CD4+ T-cell changes, and HIV RNA suppression were similar at 48 weeks. Among HIV-infected adults with mild-to-moderate KS, immediate ET provided early, nondurable clinical benefits. By 48 weeks, no clinical benefit was observed compared to use of ET as needed. Mortality was high and tumor response was low. NCT01352117.

A Systematic Review and Pooled Analysis of Studies of Oral Etoposide in Metastatic Breast Cancer.

Oral etoposide has been used as a later line therapy for metastatic breast cancer for more than twenty years. Its efficacy and clinical usefulness has been suggested in small phase II studies in the metastatic breast cancer population and the drug has also the added advantage of convenient oral administration. Despite these advantages, the place of oral etoposide in treatment of metastatic breast cancer has been challenged in the last decade due to introduction of several other chemotherapeutics, including options available orally, as well as novel targeted therapies. This report pools the data on response rates and survival from all available oral etoposide studies in order to reach a more precise estimate of the clinical benefit of the drug. A review of the literature was performed for studies of oral etoposide in metastatic breast cancer. Data were extracted from eligible studies and summary statistics derived. Calculations of pooled response rates and survival estimates were performed according to a random or fixed effect model as appropriate. The pooled estimate of Response Rate derived from twelve studies found in the English literature was 18.5% (95% CI 11.5-25.5%). The pooled estimate of Clinical Benefit Rate (CBR) was 45.8% (95% CI 38.6-53.0%) and median Overall Survival (OS) approached 1 year. Summarized adverse effects profile data show an overall manageable toxicity. This pooled analysis provides evidence of a moderate clinical effectiveness of oral etoposide in metastatic breast cancer that could be useful in situations that options are limited but active treatment still appropriate.

P2.07-046 Nivolumab Exerts Remarkable Antitumor Activity in NSCLC After an Immune-Modulating Biochemotherapy Regimen

Dose-dense cisplatin and daily oral etoposide +/- bevacizumab, mAb to the vascular endothelial-growth factor is a safe and active treatment for un-resectable NSCLC patients. It elicited remarkable Immunological effects, including rise in central-memory-T-cells and activated-dendritic cells and decline in regulatory-T-cells, potentially additive to anti-PD-1/PDL-1 immune-checkpoint inhibition. We therefore, performed a retrospective analysis aimed to evaluate both overall survival (OS) and progression free survival (PFS) in patients receiving treatment with Nivolumab, a mAb to PD-1, after they had received different first line chemotherapy regimens.

Triple therapy of vincristine, bleomycin and etoposide for children with Kaposi sarcoma: Results of a study in Malawian children.

Kaposi sarcoma (KS) is the most common paediatric cancer in human immunodeficiency virus (HIV) endemic countries of sub-Saharan Africa, but there is little research on management and outcomes. Children with KS at Queen Elizabeth Central Hospital, Blantyre, Malawi treated between August 2012 and March 2015 with six courses of vincristine, bleomycin and etoposide combination chemotherapy, including antiretroviral therapy (ART) if HIV infected, were studied and outcomes compared with previously reported results. Fifty-six children were included; 38 (68%) were male; and 48 (86%) were HIV positive, of whom 36 (77%) were on ART at diagnosis. Median age at diagnosis was 8 years (interquartile range [IQR] 3-12) and median follow-up was 16.9 months (IQR 3.4-36.4). Quality of life improved in 45 (80%) children; the median Lansky Score increased from 80% pre-treatment to 100% post-treatment. Eighteen (32%) children had complete response to treatment. At 12 months, overall survival was 71% (95% confidence interval [CI] 56-82) and event-free survival (event=death, loss to follow-up or relapse) was 50% (95% CI 36-63). At 1 year, the risk of loss to follow-up was 13.4%. In a previous, same-site, randomized controlled study of vincristine monotherapy, vincristine and bleomycin, or oral etoposide, oral etoposide monotherapy had the best outcome with survival at 12 month of 66% (95% CI 46-80) and event-free survival of 52% (95% CI 33-68); however, loss to follow-up was not reported. Overall survival, event-free survival and quality of life appear to have improved with this three-agent combination chemotherapy; however larger, randomized studies are needed to determine optimal management.

Oral etoposide in heavily pretreated metastatic breast cancer: a retrospective analysis of efficacy and safety

Oral etoposide in heavily pretreated metastatic breast cancer: a retrospective analysis of efficacy and safety

Anti-cancer activity of dose-fractioned mPE +/- bevacizumab regimen is paralleled by immune-modulation in advanced squamous NSLC patients.

Results from the BEVA2007 trial, suggest that the metronomic chemotherapy regimen with dose-fractioned cisplatin and oral etoposide (mPE) +/- bevacizumab, a monoclonal antibody to the vascular endothelial growth factor (VEGF), shows anti-angiogenic and immunological effects and is a safe and active treatment for metastatic non-small cell lung cancer (mNSCLC) patients. We carried out a retrospective analysis aimed to evaluate the antitumor effects of this treatment in a subset of patients with squamous histology. Retrospective analysis was carried out in a subset of 31 patients with squamous histology enrolled in the study between September 2007 and September 2015. All of the patients received chemotherapy with cisplatin (30 mg/sqm, days 1-3q21) and oral etoposide (50 mg, days 1-15q21) (mPE) and 14 of them also received bevacizumab 5 mg/kg on the day 3q21 (mPEBev regimen). This treatment showed a disease control rate of 71% with a mean progression free survival (PFS) and overall survival (OS) of 13.6 and 17 months respectively. After 4 treatment courses, 6 patients showing a remarkable tumor shrinkage, underwent to radical surgery, attaining a significant advantage in term of survival (P=0.048). Kaplan-Meier and log-rank test identified the longest survival in patients presenting low baseline levels in neutrophil-to-lymphocyte ratio (NLR) (P=0.05), interleukin (IL) 17A (P=0.036), regulatory-T-cells (Tregs) (P=0.020), and activated CD83+ dendritic cells (DCs) (P=0.03). These results suggest that the mPE +/- bevacizumab regimen is feasible and should be tested in comparative trials in advanced squamous-NSCLC (sqNSCLC). Moreover, its immune-biological effects strongly suggest the investigation in sequential combinations with immune check-point inhibitors.

Radiotherapy prolongs the survival of advanced non-small-cell lung cancer patients undergone to an immune-modulating treatment with dose-fractioned cisplatin and metronomic etoposide and bevacizumab (mPEBev).

Radiotherapy (RT), together with a direct cytolytic effect on tumor tissue, also elicits systemic immunological events, which sometimes result in the regression of distant metastases (abscopal effect). We have shown the safety and anti-tumor activity of a novel metronomic chemotherapy (mCH) regimen with dose-fractioned cisplatin, oral etoposide and bevacizumab, a mAb against the vasculo-endothelial-growth-factor (mPEBev regimen), in metastatic non-small-cell-lung cancer (mNSCLC). This regimen, designed on the results of translational studies, showed immune-modulating effects that could trigger and empower the immunological effects associated with tumor irradiation. In order to assess this, we carried out a retrospective analysis in a subset of 69 consecutive patients who received the mPEBev regimen within the BEVA2007 trial. Forty-five of these patients, also received palliative RT of one or more metastatic sites. Statistical analysis (a Log-rank test) revealed a much longer median survival in the group of patients who received RT [mCH vs mCH + RT: 12.1 +/-2.5 (95%CI 3.35-8.6) vs 22.12 +/-4.3 (95%CI 11.9-26.087) months; P=0.015] with no difference in progression-free survival. In particular, their survival correlated with the mPEBev regimen ability to induce the percentage of activated dendritic cells (DCs) (CD3-CD11b+CD15-CD83+CD80+) [Fold to baseline value (FBV) ≤1 vs >1: 4+/-5.389 (95%CI,0- 14.56) vs 56+/-23.05 (95%CI,10.8-101.2) months; P:0.049)] and central-memory- T-cells (CD3+CD8+CD45RA-CCR7+) [FBV ≤ 1 vs >1: 8+/-5.96 (95%CI,0-19.68) vs 31+/-12.3 (95%CI,6.94-55.1) months; P:0.045].These results suggest that tumor irradiation may prolong the survival of NSCLC patients undergone mPEBev regimen presumably by eliciting an immune-mediated effect and provide the rationale for further perspective clinical studies.