Adjuvant Capecitabine for Early Breast Cancer: 15-Year Overall Survival Results From a Randomized Trial

PURPOSE Few data are available regarding the influence of adjuvant capecitabine on long-term survival of patients with early breast cancer. METHODS The Finland Capecitabine Trial (FinXX) is a randomized, open-label, multicenter trial that evaluates integration of capecitabine to an adjuvant chemotherapy regimen containing a taxane and an anthracycline for the treatment of early breast cancer. Between January 27, 2004, and May 29, 2007, 1,500 patients with axillary node-positive or high-risk node-negative early breast cancer were accrued. The patients were randomly allocated to either TX-CEX, consisting of three cycles of docetaxel (T) plus capecitabine (X) followed by three cycles of cyclophosphamide, epirubicin, and capecitabine (CEX, 753 patients), or to T-CEF, consisting of three cycles of docetaxel followed by three cycles of cyclophosphamide, epirubicin, and fluorouracil (CEF, 747 patients). We performed a protocol-scheduled analysis of overall survival on the basis of approximately 15-year follow-up of the patients. RESULTS The data collection was locked on December 31, 2020. By this date, the median follow-up time of the patients alive was 15.3 years (interquartile range, 14.5-16.1 years) in the TX-CEX group and 15.4 years (interquartile range, 14.8-16.0 years) in the T-CEF group. Patients assigned to TX-CEX survived longer than those assigned to T-CEF (hazard ratio 0.81; 95% CI, 0.66 to 0.99; P = .037). The 15-year survival rate was 77.6% in the TX-CEX group and 73.3% in the T-CEF group. In exploratory subgroup analyses, patients with estrogen receptor–negative cancer and those with triple-negative cancer treated with TX-CEX tended to live longer than those treated with T-CEF. CONCLUSION Addition of capecitabine to a chemotherapy regimen that contained docetaxel, epirubicin, and cyclophosphamide prolonged the survival of patients with early breast cancer.

Severe Generalized Weakness, Paraplegia following administration of Oxaliplatin in a patient with refractory T-cell non-Hodgkin lymphoma: A case report

Introduction Oxaliplatin is a third-generation platinum compound that used extensively for the treatment of various types of cancer especially gastrointestinal neoplasms. The main dose-limiting toxicities of oxaliplatin are hematological toxicity and peripheral sensory neuropathy. Case report A 42-year-old man with refractory peripheral T-cell lymphoma (PTCL) was admitted to receive GEMOX chemotherapy regimen (gemcitabine, oxaliplatin). Three days after receiving his third cycle of chemotherapy regimen, he was re-admitted to the emergency department with complaint of severe generalized weakness, and paraplegia in the lower extremities. According to clinical and para-clinical findings, chronic sensorimotor polyneuropathy with ongoing axonal loss was confirmed. Management & Outcome Intravenous dexamethasone 8 mg three times daily was started at the time of admission for the patient. Muscle weakness and sensory impairment improved dramatically within 10 days and the patient was able to walk with assistance. Discussion Several cases of neuropathy following oxaliplatin and only one case with gemcitabine-based chemotherapy regimen have been previously reported. However, motor symptoms are rare unless in the setting of acute neuropathy due to oxaliplatin. The most striking finding of our study was the incidence of a chronic sensorimotor axonaldemyelinating polyneuropathy in a patient who were subjected to oxaliplatin therapy. In conclusion, we report a case of severe generalized weakness and paraplegia following administration of Oxaliplatin.

Сurrent options and perspectives of systemic therapy for advanced or metastatic adrenocortical cancer

Adrenocortical cancer is an orphan tumor with poor prognosis. The combination of EDP chemotherapy regimen and mitotane is the standard for the first‑line therapy. But there are no effective options for the second and consequent lines of therapy. The standard of second‑line therapy is the combination of gemcitabine, capecitabine and mitotane, which provides an objective response in 4–7 % of patients. Achievement of the therapeutic concentration of mitotane is the most important predictive factor of efficiency of GemCap + mitotane regimen, and, therefore, it is recommended to continue mitotane therapy after progression to mitotane. Recently, many researches regarding the efficiency of targeted and immunotherapy of adrenocortical cancer have been published. However, there are no standards for the third and subsequent lines of treatment. This review outlines the current views and perspectives of systemic therapy for advanced and metastatic adrenocortical cancer.

The Elephant in The Room: AML Relapse Post Allogeneic Hematopoietic Cell Transplantation

Relapsed acute myeloid leukemia (AML) following allogeneic hematopoietic cell transplantation (allo-HCT) is an unfavorable event associated with a poor prognosis, particularly for patients with early relapses. It usually arises from resistant leukemic blasts that escaped both preparative chemotherapy regimen and the graft-versus-leukemia (GVL) effect. Independent from the choice of salvage treatment, only minority of patients can achieve durable remissions. In recent years, better understanding of the disease relapse biology post allo-HCT allowed the application of newer strategies that could induce higher rates of remission, and potential longer survival. Those strategies aim at optimizing drugs that have a direct anti-leukemia activity by targeting different oncogenic mutations, metabolism pathways or surface antigens, and concurrently enhancing the immune microenvironment to promote GVL effect. This review discusses the current treatment landscape of AML relapse post allo-HCT.

FOLFIRI (folinic acid, fluorouracil, and irinotecan) increases not efficacy but toxicity compared with single-agent irinotecan as a second-line treatment in metastatic colorectal cancer patients: a randomized clinical trial

Background: FOLFIRI [irinotecan, folinic acid (CF), and fluorouracil] is considered a standard second-line chemotherapy regimen for patients with metastatic colorectal cancer (mCRC) who failed first-line XELOX/FOLFOX regimens. However, it remains unknown whether fluorouracil is still necessary in this case. This trial was designed to test the superiority of FOLFIRI over single-agent irinotecan as a second-line treatment for patients with mCRC. Methods: This randomized clinical trial was conducted in five hospitals in China. From 4 November 2016 to 17 January 2020, patients aged 18 years or older with histologically confirmed unresectable mCRC and who had failed first-line XELOX/FOLFOX regimens were screened and enrolled. Patients were randomized to receive either FOLFIRI or irinotecan. The primary endpoint was progression-free survival (PFS). Secondary endpoints included overall survival (OS), objective response rate (ORR), and toxicity. Data were analyzed on an intention-to-treat basis. Results: A total of 172 patients with mCRC were randomly treated with FOLFIRI ( n = 88) or irinotecan ( n = 84). The median PFS was 104 and 112 days (3.5 and 3.7 months) in the FOLFIRI and irinotecan groups, respectively [hazard ratio (HR) = 1.084, 95% confidence interval (CI) = 0.7911–1.485; p = 0.6094], and there was also no significant difference in OS and ORR between the two groups. The incidence of the following adverse events (AEs) was significantly higher in the FOLFIRI group than in the irinotecan group: any grade AEs including leucopenia (73.9% versus 55.4%), neutropenia (72.7% versus 56.6%), thrombocytopenia (31.8% versus 18.1%), jaundice (18.2% versus 7.2%), mucositis (40.9% versus 14.5%), vomiting (37.5% versus 21.7%), and fever (19.3% versus 7.2%) and grade 3–4 neutropenia (47.7% versus 21.7%). Conclusion: This is the first head-to-head trial showing that single-agent irinotecan yielded PFS, OS, and ORR similar to FOLFIRI, with a more favorable toxicity profile; therefore, it might be a more favorable standard chemotherapy regimen for mCRC patients who failed first-line XELOX/FOLFOX regimens. Trial registration: This study is registered with ClinicalTrials.gov, number NCT02935764, registered 17 October 2016, https://clinicaltrials.gov/ct2/show/NCT02935764 .

Study of Gemcitabine Plus Nab-Paclitaxel-Based Chemotherapy Regimen as First-Line Treatment in Metastatic Pancreatic Carcinoma

Background The purpose of this study was to study the effectiveness of gemcitabine and nab-paclitaxel combination as first-line chemotherapy regimen for the treatment of metastatic pancreatic cancer. There is scarcity of data regarding efficacy and toxicity profile of this combination in Indian population. Aims and Objectives The primary aim of this study was to assess efficacy of this regimen, for which evaluation done in terms of the objective response rate, progression-free survival (PFS), and overall survival. Safety data were also evaluated. Materials and Methods In this prospective study, gemcitabine plus nab-paclitaxel combination chemotherapy was given as first line in metastatic pancreatic carcinoma patients till progression or appearance of grade 3/4 toxicities with treatment. Results The study was performed in 30 patients comprising 18 (60%) males and 12 (40%) females. The median age was 60 years. Median number of cycles administered were six cycles per patient. Seventeen patients (56.67%) had a partial response and 0% had complete response. A total of seven (23.3%) patients progressed on chemotherapy and six (20%) had stable disease (SD). The disease control rate (responses and SD) was 76.7%. The median PFS was 5.75 months. There was no statistically significant difference in terms of response rates and baseline CA 19-9 levels. Most common toxicities were hematological toxicities with rates of grade 3/4 anemia and neutropenia of 20%. Among nonhematological toxicities, nausea (46.67%) and fatigue (30%) were the commonest. Conclusion Combination of gemcitabine and nab-paclitaxel is active and well tolerated in advanced pancreatic carcinoma. To the best of our knowledge, this is the first such study conducted in India.

Modern approaches to pharmacotherapy of tuberculosis infection in children

Anti-TB drugs for children: Aetiotropic therapy is used for the treatment of tuberculosis (TB) in children, as well as in adult patients. Anti-tuberculosis drugs (anti-TB drugs) are divided into 3 lines, taking into account drug sensitivity in Mycobacterium tuberculosis (MBT). First-line anti-TB drugs (basic) are used to treat TB caused by drug-susceptible MBT. Second- and third-line (reserve) drugs are recommended for the treatment of MBT-induced multidrug-resistant (MDR) and extensively drug-resistant (XDR) TB, respectively. Stages and regimens to treat tuberculosis: Chemotherapy of tuberculosis in children is carried out in 2 stages (intensive treatment and continuation of treatment) and includes 5 regimens. Each regimen assumes a certain combination of anti-TB drugs, indicating the duration and frequency of their administration. The final chemotherapy regimen is chosen only according to the results of determining the drug sensitivity. To improve the TB epidemic among children, it is important to improve the regimens for the use of anti-TB drugs. The effectiveness of anti-tuberculosis pharmacotherapy is largely determined by the MBT sensitivity and the rational choice of the chemotherapy regimen. The wrong choice of a chemotherapy regimen or its violation threatens to reduce the effectiveness of pharmacotherapy and expand the spectrum of resistance of the pathogen. The development of fixed-dose combination anti-TB drugs and special dosage forms for children will improve the quality of chemotherapy and adherence to treatment. Pharmacoeconomic studies are needed to increase the effectiveness of drug pharmacotherapy for tuberculosis infection in children and to optimize the costs of its implementation.

Unplanned 30-Day Readmissions after Hyper-CVAD Chemotherapy in Patients with Acute Lymphoblastic Leukemia

Introduction: The aim of this study was to investigate the rate and causes of re-hospitalization in the first 30 days after Hyper-CVAD chemotherapy in all patients with acute lymphoblastic leukemia. Methods: This descriptive, analytical and cross-sectional study was performed on 827 admissions in ALL patients aged 18 years and older with unplanned hospitalization after HyperCVAD chemotherapy in less than 30 days’ post chemotherapy from April 2016 to April 2018 in Hematology and medical oncology department. Results: The rate of unplanned re-admission was 9.91% in all patients. Mean follow-up time was 13.77 ± 6.26 months and the mean age of patients was 35.55 ± 14.6 years. Re-admission rate was more frequent in men (65.7%) and most patients were readmitted only once. The mean duration of re-admission was 8.2±4.15 days and most patients were re-admitted after cycles IB, IIIB and IVB of hyper-CVAD chemotherapy. The most common causes of readmission were febrile neutropenia and pancytopenia. Except for significant changes in CBC, no significant changes were observed in other laboratory tests. Urine culture and blood culture were reported positive in 13.6% and 31.57% respectively, and E-coli was the most common organism isolated from cultures. Conclusion: We found increased rate of re-admission following hyper-CVAD chemotherapy in patients with acute lymphoblastic leukemia which was due to side effects of chemotherapy regimen. It seems to be important not only for high rate of mortality and morbidity in patients resulting from this chemotherapy regimen, but also imposing the heavy cost on health system. Therefore, more effective preventive measures are necessary and useful.