Bevacizumab plus infusional 5-fluorouracil, leucovorin and irinotecan for advanced colorectal cancer that progressed after oxaliplatin and irinotecan chemotherapy： A pilot study

AIM： To evaluate the combination of bevacizumab with infusional 5-fluorouracil （5-FU）, leucovorin （LV） and irinotecan （FOLFIRI） in patients with advanced colorectal cancer （CRC） pretreated with combination regimens including irinotecan and oxaliplatin. METHODS： Fourteen patients （median age 56 years） with advanced CRC, all having progressed after oxaliplatin- and irinotecan-based combination chemotherapy, were enrolled in this study. Patients were treated with 2 h infusion of irinotecan 150 mg/m2 on d 1, plus bevacizumab 5 mg/kg iv infusion for 90 min on d 2, and iv injection of LV 20 mg/m2 followed by a bolus of 5-FU 400 mg/m2 and then 22 h continuous infusion of 600 mg/m2 given on two consecutive days every 14 d. RESULTS： The median number of cycles of chemotherapy was six （range 3-12）. The response rate was 28.5%, one patient had a complete response, and three patients had a partial response. Eight patients had stable disease. The median time to progression was 3.9 mo （95% CI 2.0-8.7）, and the median overall survival was 10.9 mo （95% CI 9.6-12.1）. Grade 3/4 neutropenia occurred in five patients, and two of these developed neutropenic fever. Grade 3 hematuria and hematochezia occurred in one. Grade 2 proteinuria occurred in two patients. However, hypertension, bowel perforation or thromboembolic events did not occur in a total of 90 cycles. CONCLUSION： Bevacizumab with FOLFIRI is well tolerated and a feasible treatment in patients with heavily treated advanced CRC.     

Cetuximab plus irinotecan in pretreated metastatic colorectal cancer patients: the ELSIE study

AIM:To evaluate the efficacy and safety of cetuxim-ab plus irinotecan in irinotecan-refractory metastatic colorectal cancer (mCRC) patients from South-East Asia and Australia. METHODS:In this open-label,phase Ⅱ study,the main eligibility criteria were epidermal growth factor receptor-positive mCRC with progressive disease within 3 mo of an irinotecan-based regimen as the most recent chemotherapy. Patients received cetuximab 400 mg/m2 initially,then 250 mg/m2 every week,with the same regimen of irinotecan on...     

Phase II trial of adriamycin in the treatment of advanced or recurrent endometrial carcinoma: a Gynecologic Oncology Group study.

Forty-three patients with advanced or recurrent endometrial carcinoma no longer amenable to management with surgery or radiotherapy were treated with adriamycin. Sixteen of the 43 patients demonstrated objective response to drug therapy with a greater than or equal to 50% reduction in the size of measurable disease. There were 11 complete responses among these 16 responders. Responders had a significantly better survival than nonresponders (P less than 0.05). Initial performance status was the only factor of demonstrable prognostic significance. Toxicity was similar to that observed in other phase II trials of adriamycin. Adriamycin, based on these data, is an active agent in the treatment of advanced or recurrent endometrial carcinoma.     

Vindesine, carmustine, doxorubicin, and prednisone (EBAP) in recurrent lymphomas: a Southwest Oncology Group study

Seventy-eight patients with Hodgkin's disease and non-Hodgkin's lymphoma who had failed prior chemotherapy or radiation therapy were treated with a combination of vindesine, carmustine, doxorubicin, and prednisone (EBAP). Outpatient therapy was administered at 21-day intervals. Complete and partial responses were seen in 32 patients (41%). The response rate was higher for Hodgkin's disease (59%) than for non-Hodgkin's lymphoma (31%). The median duration of response was 31 weeks in both groups, with a median survival of all patients of 35 weeks (responders, 122 weeks; nonresponders, 16 weeks). Myelotoxicity was greater using EBAP than in the earlier reported program with vincristine, carmustine, doxorubicin, and prednisone, and in the absence of higher response rates does not support the use of vindesine over vincristine in combination programs using nitrosoureas, anthracyclines, and prednisone.     

Study protocol for a multi-institutional randomized phase III study comparing combined everolimus plus lanreotide therapy and everolimus monotherapy in patients with unresectable or recurrent gastroenteropancreatic neuroendocrine tumors; Japan Clinical Oncology Group Study JCOG1901 (STARTER-NET study)

Everolimus is recognized as one of the standard drugs for the treatment of unresectable or recurrent gastroenteropancreatic neuroendocrine tumors (NET). However, recent evidence has suggested that addition of somatostatin analogs to everolimus may yield better survival outcomes as compared to everolimus alone. In April 2020, we have initiated a randomized phase III trial in Japan, to confirm the superiority of combined everolimus plus lanreotide therapy over everolimus monotherapy in patients with unresectable or recurrent gastroenteropancreatic NETs with poor prognostic factors (Ki-67 labeling index: LI 5%–20% or Ki-67 LI < 5% with diffuse liver metastases). We plan to enroll a total of 250 patients from 76 institutions over an accrual period of 5 years. The primary endpoint is progression-free survival. The key secondary endpoint is overall survival, with response rate, disease control rate, and proportion of patients with adverse events as the other secondary endpoints. This trial is registered with the Japan Registry of Clinical Trials as jRCT1031200023 [https://jrct.niph.go.jp/en-latest-detail/jRCT1031200023].     

Clinical and prognostic features of plasmacytomas: a multicenter study of Turkish Oncology Group-Sarcoma Working Party

To identify the outcomes of prognostic factors of solitary plasmacytoma mainly treated with local radiotherapy (RT). The data were collected from 80 patients with solitary plasmacytoma (SP). Forty patients (50.0%) received radiotherapy (RT) alone while 38 of them (47.5%) were treated with surgery (S) and RT. The median radiation dose was 46 Gy (range 30-64). The median follow up was 2.41 years (range 0.33-12.33). Ten-year overall survival (OS) and local relapse-free survival (LRFS) were 73% and 94%, respectively. The median progression-free survival (PFS) and multiple myeloma-free survival (MMFS) were 3.5 years and 4.8 years, respectively. On multivariate analyses, the favorable factors were radiotherapy dose of > or =50 Gy and RT + S for PFS and younger age for MMFS. For the patients with medullary plasmacytoma, the favorable factor was younger age for MMFS. RT at > or =50 Gy and RT + S may be favorable prognostic factors on PFS. Younger patients, especially with head-neck lesion and without pre-RT macroscopic tumor, seem to have the best outcome when treated with RT +/- S. Progression to MM remains as the main problem especially for older patients.     

Morphology, cytogenetics, and survival in myelodysplasia with del(20q) or ider(20q): a multicenter study

Isochromosome of the long arm of chromosome 20 with interstitial loss of material [ider(20q)] is a rare cytogenetic abnormality reported in myelodysplastic syndrome (MDS), with neither specific morphological pattern nor clear prognostic significance. The aim of this retrospective multicentric study is to compare the peripheral blood and bone marrow morphology of MDS patients with ider(20q) (n?=?13) and del(20q) (n?=?21) and controls (n?=?47) in order to investigate whether the ider(20q) harbors specific morphological features. The secondary objective is to compare the outcome of patients from both groups. This study performed on the largest cohort of MDS patients with ider(20q) is the first that identifies specific morphological features (hypogranulated and vacuolized neutrophils and neutrophil erythrophagocytosis) allowing the identification of this cytogenetic abnormality with high sensitivity (70%) and specificity (85.7%). Suspected ider(20q) by morphology should therefore support targeted FISH tests in case of non informative karyotype. This combined approach will allow a better estimation of the prevalence of this underdiagnozed entity. The overall survival and progression-free survival did not statistically differ in both groups. However, hypogranulated and vacuolized neutrophils were significantly associated with survival.     

Carboplatin plus paclitaxel in the treatment of advanced or recurrent endometrial carcinoma

Purpose To evaluate the efficacy and safety of the combination of carboplatin plus paclitaxel in patients with advanced, metastatic and recurrent endometrial cancer. Methods Medical records were retrospectively reviewed to identify endometrial cancer patients treated in the Gynecologic Cancer Program of the Cleveland Clinic with carboplatin/paclitaxel who had both a histologic diagnosis of endometrial adenocarcinoma and either measurable (CT scan, physical examination) or evaluable (CA-125 criteria) disease. Results From 1994 to 2003, 22 individuals (median age 65 years) meeting the above noted criteria received a total of 23 courses of carboplatin (AUC 4–6)/paclitaxel (135–175 mg/m2) administered on a 21-day schedule (median six cycles/patient). The overall response rate was 87% (20/23). The most common toxicity was hematologic. Five patients required dose reductions due to excessive toxicity (three hematologic, one gastrointestinal, one fatigue). There were no treatment related deaths. With a median follow-up of 42 months, 13 patients have died of progressive cancer, while four currently have no evidence of disease at the time of last follow-up. Conclusions The combination of carboplatin plus paclitaxel demonstrates substantial biological activity in endometrial adenocarcinoma. The safety and efficacy of this regimen makes it an attractive option for first-line chemotherapy in patients with advanced or recurrent endometrial carcinoma.     

High-dose methotrexate with leucovorin rescue plus vincristine in advanced sarcoma: a Southwest Oncology Group study

Twenty-six evaluable patients with advanced soft tissue and bony sarcomas refractory to chemotherapy were treated with vincristine plus high-dose methotrexate and leucovorin rescue. A 14% response rate was observed among 14 patients presenting with refractory soft tissue sarcomas. No responses were observed among 12 patients with bony sarcoma. Toxic reaction with nausea, vomiting, nephrotoxicity, and myelosuppression was manageable. While this study did demonstrate activity of this regimen in doxorubicin-refractory patients, the duration of the responses was relatively brief. Thus, the clinical utility of such a regimen is questionable.     

Venetoclax plus bendamustine-rituximab or bendamustine-obinutuzumab in chronic lymphocytic leukemia: final results of a phase Ib study (GO28440)

Venetoclax (Ven), an orally administered, potent BCL-2 inhibitor, has demonstrated efficacy in chronic lymphocytic leukemia (CLL) in combination with rituximab (R) or obinutuzumab (G). Our aim was to investigate the addition of bendamustine (B) to these Ven-containing regimens in relapsed/refractory (R/R) or first-line (1L) CLL. This multi-arm, nonrandomized, open-label, phase Ib study was designed to evaluate the maximum tolerated dose (MTD) and safety/tolerability of Ven with BR/BG, with 3+3 dose-escalation followed by safety expansion. Patients received Ven (schedule A) or BR/BG first (schedule B) to compare safety and determine dose/schedule for expansion. Six Ven-BR/-BG cycles were to be administered, then Ven monotherapy until disease progression (R/R) or fixed-duration 1- year treatment (1L). Overall, 33 R/R and 50 1L patients were enrolled. No dose-limiting toxicities were observed (doses 100–400 mg), and the MTD was not reached. Safety was similar between schedules; no tumor lysis syndrome occurred during dose-finding. Schedule B and Ven 400 mg were chosen for expansion. The most frequent grade 3–4 toxicity was neutropenia: R/R 64%, 1L Ven-BR 85%, 1L Ven-BG 55%. Grade 3–4 infection rate was: R/R 27%, 1L Ven-BR 0%, 1L Ven-BG 27%. During expansion, one clinical and two laboratory tumor lysis syndrome cases occurred. Fewer than half the patients completed six combination therapy cycles with all study drugs; rates of bendamustine discontinuation were high. Overall response rate was 91% in R/R and 100% in 1L patients (16 of 49 1L patients received Ven for >1 year). In conclusion, addition of bendamustine to Ven-R/-G increased toxicity without apparent efficacy benefit (clinicaltrial gov. Identifier: {"type":"clinical-trial","attrs":{"text":"NCT01671904","term_id":"NCT01671904"}}NCT01671904).     

Familial Mediterranean fever (FMF) in Turkey: results of a nationwide multicenter study

Familial Mediterranean fever (FMF) is an autosomal recessive disease that is prevalent among eastern Mediterranean populations, mainly non-Ashkenazi Jews, Armenians, Turks, and Arabs. Since a large proportion of all the FMF patients in the world live in Turkey, the Turkish FMF Study Group (FMF-TR) was founded to develop a patient registry database and analyze demographic, clinical, and genetic features. The cohort was composed of 2838 patients (mean age, 23.0 +/- 13.33 yr; range, 2-87 yr), with a male:female ratio of 1.2:1. There was a mean period of 6.9 +/- 7.65 years from disease onset to diagnosis; the period was about 2 years shorter for each decade since 1981. Ninety-four percent of patients were living in the central-western parts of the country; however, their familial origins (70% from the central-eastern and Black Sea regions) reflected not only the ongoing east to west migration, but also the historical roots of FMF in Turkey. Patients' clinical features included peritonitis (93.7%), fever (92.5%), arthritis (47.4%), pleuritis (31.2%), myalgia (39.6%), and erysipelas-like erythema (20.9%). Arthritis, arthralgia, myalgia, and erysipelas-like erythema were significantly more frequent (p < 0.001) among patients with disease onset before the age of 18 years. Genetic analysis of 1090 patients revealed that M694V was the most frequent mutation (51.4%), followed by M680I (14.4%) and V726A (8.6%). Patients with the M694V/M694V genotype were found to have an earlier age of onset and higher frequencies of arthritis and arthralgia compared with the other groups (both p < 0.001). In contrast to other reported studies, there was no correlation between amyloidosis and M694V homozygosity in this cohort. However, amyloidosis was still remarkably frequent in our patients (12.9%), and it was prevalent (27.8%) even among the 18 patients with a disease onset after age 40 years. Twenty-two patients (0.8%) had nonamyloid glomerular diseases. The high prevalence of vasculitides (0.9% for polyarteritis nodosa and 2.7% for Henoch-Schonlein purpura) and high frequency of pericarditis (1.4%) were striking findings in the cohort. Phenotype II cases (those patients with amyloidosis as the presenting or only manifestation of disease) were rare (0.3% or less). There was a high rate of a past diagnosis of acute rheumatic fever, which suggested a possible misdiagnosis in children with FMF presenting with recurrent arthritis. To our knowledge, this is the largest series of patients with FMF reported from 1 country. We describe the features of the disease in the Turkish population and show that amyloidosis is still a substantial problem.     

Venous thromboembolism and cancer: guidelines of the Italian Association of Medical Oncology (AIOM)

Thromboembolic complications represent one of the most important cause of morbidity and mortality in cancer patients. Although several data have been published demonstrating the strong association between cancer and venous thromboembolism (VTE), there is poor perception, among oncologists, of the level of risk of thrombosis and of relevance of managing VTE in these patients. The Associazione Italiana di Oncologia Medica (AIOM) has provided some recommendations to direct clinical practice according to evidence-based data concerning cancer and VTE. In fact, we conducted an extensive literature review (1996-2005) to produce evidence-based recommendations to improve perceptions of the magnitude of this risk among Italian medical and surgical oncologists and alert on the new approaches to prophylaxis and treatment of VTE in cancer patients. Levels of evidence are given according to a five-point rating system, and similarly for each key recommendation a five-point rating system suggests if the evidence is strong and indicate that the benefits do, or do not, outweigh risks and burden.     

Management of sepsis in neutropenic patients: 2014 updated guidelines from the Infectious Diseases Working Party of the German Society of Hematology and Medical Oncology (AGIHO)

Sepsis is a major cause of mortality during the neutropenic phase after intensive cytotoxic therapies for malignancies. Improved management of sepsis during neutropenia may reduce the mortality of cancer therapies. Clinical guidelines on sepsis treatment have been published by others. However, optimal management may differ between neutropenic and non-neutropenic patients. Our aim is to give evidence-based recommendations for haematologist, oncologists and intensive care physicians on how to manage adult patients with neutropenia and sepsis.     

Sex-specific prediction equations for Vmax(FRC) in infancy: a multicenter collaborative study

Measurements of maximal flow at functional residual capacity (Vmax(FRC)) from partial forced expiratory maneuvers remain the most popular method for assessing small airway function in infants and young children. However, the lack of appropriate reference data that are both applicable outside the centers that developed them and reflect the normal variability between healthy subjects has limited interpretation of Vmax(FRC) results in both clinical practice and research. To address this problem, we collated Vmax(FRC) data from 459 healthy infants (226 boys) tested on 654 occasions during the first 20 months of life from three collaborating centers. Multiple linear regression analysis indicated that sex, age, and length were important predictors of Vmax (FRC), which was, on average, 20% higher in girls than in boys during the first 9 months of life. (Vmax(FRC))0.5 (ml x second(-1)) = 4.22 + 0.00210 x length2 (cm) for boys (RSD = 3.01; R2 = 0.48), and -1.23 + 0.242 x length for girls (RSD = 2.72; R2 = 0.49). Alternative models incorporating both age and length z scores are also described. Failure to use sex-specific prediction equations for Vmax(FRC) may preclude detection of clinically significant changes in girls and lead to false reports of diminished airway function in boys. Appropriate use of z scores, which indicate a "normal" range (z scores of 0 +/- 2) for Vmax(FRC), during infancy should also improve interpretation of both clinical and research studies.