Cisplatin and Irinotecan as First-Line Chemotherapy for Previously Untreated Metastatic Thymic Carcinoma: Updated Analysis

Platinum-based chemotherapy is the de facto standard treatment for metastatic or unresectable thymic carcinoma. The optimal chemotherapy regimen has not yet been determined, including whether this should be combined with a second- or third-generation anti-cancer agent. We retrospectively evaluated the data of patients with metastatic or unresectable thymic carcinoma who were treated with a combination of cisplatin and irinotecan as first-line chemotherapy between 2002 and 2021 (trial registration UMIN000012175). The primary endpoint was response rate according to the RECIST criteria version 1.1. Secondary endpoints were disease control rate, progression-free survival (PFS), overall survival (OS), and toxicity (adverse events). Some patients analyzed in this study were also included in the previous trial, which was terminated early. For this analysis, we included 18 patients with a median age of 56 years and an Eastern Cooperative Oncology Group performance status of 0 or 1. All patients had clinical stage IVa or IVb thymic carcinoma according to the Masaoka-Koga staging system. The response rate was 44% and the disease control rate was 89%. The median PFS was 8.4 months (95% confidence interval (CI): 2.7–11.6 months) and the median OS was 45.6 months (95% CI: 15.7–69.1 months). Grade 3 or worse hematological toxicity was observed in 5 patients and grade 3 or worse non-hematological toxicity was observed in 3 patients. None of the patients developed febrile neutropenia, and no treatment-related deaths occurred. Thus, the combination of cisplatin and irinotecan as first-line chemotherapy for metastatic thymic carcinoma showed efficacy and acceptable toxicity.

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.

Safety and efficacy of pegylated recombinant human granulocyte colony-stimulating factor during concurrent chemoradiotherapy for small-cell lung cancer: a retrospective, cohort-controlled trial

Objective To investigate pegylated recombinant human granulocyte colony-stimulating factor (PEG-rhG-CSF) safety and efficacy in preventing hematological toxicity during concurrent chemoradiotherapy (CCRT) for small-cell lung cancer (SCLC). Methods We retrospectively assessed 80 SCLC patients treated with CCRT from January 2013 to December 2018 who received PEG-rhG-CSF within 48 hours after the end of chemotherapy, defined as prophylactic use, as the experimental group. An additional 80 patients who were not treated with PEG-rhG-CSF were matched 1:1 by the propensity score matching method and served as the control group. The main observations were differences in hematological toxicity, neutrophil changes, febrile neutropenia (FN) incidence and adverse reactions. Progression-free survival (PFS) and overall survival (OS) were analyzed with regular assessment and follow-up. Results The leukocyte, neutrophil, erythrocyte, and platelet counts and hemoglobin level decreased after CCRT, but the experimental group had slightly higher leukocyte and neutrophil counts than the control group (P<0.05). The incidences of grade III-IV leukopenia (18.75% vs. 61.25%) and neutropenia (23.75% vs. 67.5%) in the experimental group were significantly lower than those in the control group (P<0.05). The absolute neutrophil count was 4.17±0.79 on day 1 and peaked (6.81±2.37) on day 10 in the experimental group; the value in the control group was 2.81±0.86 on day 1. It decreased significantly and reached the minimum (0.91±0.53) on day 10 (P<0.05). The experimental group had a lower FN incidence than the control group (P<0.05). There was also no significant acute esophagitis or pulmonary toxicity. The treatment had no significant effect on PFS (11.4 vs. 8.7, P=0.958) or OS (23.9 vs. 17.3, P=0.325) over an 18.6-month median follow-up time. Conclusion PEG-rhG-CSF has good efficacy and safety in preventing hematological toxicity in SCLC patients during CCRT and has no significant effects on PFS or OS.

TYMS 3′-UTR Polymorphism: A Novel Association with FOLFIRINOX-Induced Neurotoxicity in Pancreatic Cancer Patients

Pancreatic ductal adenocarcinoma (PDAC) is a highly fatal malignancy that has the worst 5-year survival rate of all of the common malignant tumors. Surgery, chemotherapy, and/or chemoradiation remain the main tactics for PDAC treatment. The efficacy of chemotherapy is often compromised because of the substantial risk of severe toxicities. In our study, we focused on identification of polymorphisms in the genes involved in drug metabolism, DNA repair and replication that are associated with inter-individual differences in drug-induced toxicities. Using the microarray, we genotyped 12 polymorphisms in the DPYD, XPC, GSTP1, MTHFR, ERCC1, UGT1A1, and TYMS genes in 78 PDAC patients treated with FOLFIRINOX. It was found that the TYMS rs11280056 polymorphism (6 bp-deletion in TYMS 3′-UTR) predicted grade 1–2 neurotoxicity (p = 0.0072 and p = 0.0019, according to co-dominant (CDM) and recessive model (RM), respectively). It is the first report on the association between TYMS rs11280056 and peripheral neuropathy. We also found that PDAC patients carrying the GSTP1 rs1695 GG genotype had a decreased risk for grade 3–4 hematological toxicity as compared to those with the AA or AG genotypes (p = 0.032 and p = 0.014, CDM and RM, respectively). Due to relatively high p-values, we consider that the impact of GSTP1 rs1695 requires further investigation in a larger sample size.

Good Tumor Response to Chemoradioimmunotherapy in dMMR/MSI-H Advanced Colorectal Cancer: A Case Series

PurposeImmune checkpoint blockade has led to a significant improvement of patient survival in metastatic colorectal cancer (CRC) with DNA mismatch repair-deficiency (dMMR)/microsatellite instability-high (MSI-H). However, not all these patients are sensitive to monoimmunotherapy. We firstly presented a case series of advanced dMMR/MSI-H CRCs treating with PD-1 inhibitor-based chemoradioimmunotherapy (CRIT).Methods and MaterialsWe assessed the short-term efficacy and safety of CRIT in advanced dMMR/MSI-H CRCs, and also did next-generation sequencing (NGS) assays.ResultsOur analysis included five advanced dMMR/MSI-H CRCs who have received toripalimab-based CRIT. Toripalimab was given 240mg every three weeks, and the radiation dose was 45-50 gray in 25 fractions. Chemotherapy regimens consisted of CAPOX in three patients, capecitabine in one patient, and mFOLFOX6 in one patient. Initially, two patients displayed complete response (CR), and three patients achieved partial response (PR) on imaging findings. Afterwards, one PR patient was confirmed pathological complete response after surgery, leading to three CR cases in total. Hematological toxicity was the most common adverse effect, and only two patients developed mild immune-related adverse effects besides. All the treatment-related adverse events were under control. Based on the NGS results, the median intratumor heterogeneity was 0.19 (range 0-0.957), which was less in CR patients than PR patients (P = 0.019). Genetic mutations at DNA damage repair genes and the JAK1 gene were also observed.ConclusionsFor advanced dMMR/MSI-H CRC, anti-PD-1 based CRIT is effective and safe. Further studies are required to better clarify the potential role and mechanism of CRIT as a viable therapeutic strategy in this population.

Multiple Colorectal Mucosa-Associated Lymphoid Tissue Lymphoma Successfully Treated with Chemotherapy

The standard treatment for colorectal mucosa-associated lymphoid tissue (MALT) lymphoma has not yet been established due to the rarity of the disease. Here, we report a case of long-term response to chemotherapy for colorectal MALT lymphoma (stage I). A 77-year-old frail female patient with diabetes mellitus and dementia developed melena of unknown etiology, and a colonoscopy was performed at a nearby hospital. A biopsy suggested malignant lymphoma, and she was referred to our department. As a result of re-examination of colonoscopy, a total of 3 submucosal tumor-like lesions were confirmed. Of these, a biopsy of the lesions in the ascending colon and rectum was performed, and MALT lymphoma was diagnosed on the basis of the histopathological findings. Following close examination, no other lymphoma lesions were found, and the patient was diagnosed with primary colorectal MALT lymphoma, stage I. After 1 course of R-THP-COP chemotherapy (rituximab + cyclophosphamide, pirarubicin, vincristine, and prednisone), the rectal lesion was confirmed to have almost disappeared endoscopically, and lymphoma cells were not found histopathologically. The patient was determined to be in complete remission (CR). However, due to hematological toxicity and a slight worsening of glucose control, the second chemotherapy course was changed to the BR regimen (rituximab + bendamustine), and 4 courses were performed (5 total courses of chemotherapy). Currently, &#x3e;3 years have passed since reaching CR, and the patient is alive without recurrence.

GSTP1 Ile105Val polymorphism among North Indian lung cancer patients treated using monotherapy and poly-pharmacy

Background Genetic polymorphism within the P1 isoenzyme of the Glutathione-S-Transferase (GST) family is found to modulate and alter the enzyme activity of GSTP1 protein and thus may result in a change of sensitivity to platinum-based chemotherapy. We investigated the relationship between GSTP1 Ile 105 Val polymorphisms and overall survival, treatment response, and for both hematological and non-hematological toxicity of advanced North Indian lung cancer patients undergoing platinum-based double chemotherapy. Methods The polymorphism of GSTP1 Ile 105 Val in North Indian lung cancer patients was assessed by polymerase chain reaction-restriction fragment length polymorphism. A total of 682 lung cancer patients were enrolled in the study, and it was observed that patients who were carrying both the mutant alleles ( Val/Val) for the GSTP1 polymorphism showed a higher trend of median survival time (MST) as compared to the patients bearing the wild type of genotype (Ile/Ile) (MST = 8.30 vs. 7.47, p = 0.56). Based on toxicity profiling, we observed that lung cancer patients with the mutant genotype of GSTP1 (Val/Val) had an increased risk of leukopenia (OR = 2.41; 95% CI = 1.39-4.18, p = 0.001) as compared to subjects carrying both copies of the wild alleles (Ile/Ile). Our data suggested that patients with heterozygous genotype (Ile/Val) had a 2.14-fold increased risk of developing severe anemia (OR = 2.14, 95% CI = 0.97-4.62, p = 0.03). Our data also showed that in small cell lung carcinoma (SCLC) patients' polymorphism of GSTP1 was associated with thrombocytopenia (χ2 test = 7.32, p = 0.02). Conclusions Our results suggest that GSTP1 Ile105Val polymorphism could be a predictive biomarker for hematological toxicity, like leukopenia and anemia, but not thrombocytopenia or neutropenia

Upfront Treatment of Pediatric High-Risk Neuroblastoma With Chemotherapy, Surgery, and Radiotherapy Combination: The CCCG-NB-2014 Protocol

PurposeThe Chinese Children’s Cancer Group developed the CCCG-NB-2014 study to formulate optimal treatment strategies for high-risk (HR) neuroblastoma (NB). The safety and efficacy of this protocol were evaluated.MethodPatients with newly diagnosed neuroblastoma and defined as HR according to the Children’s Oncology Group study were included. They were treated with a combination of chemotherapy, surgery, and radiotherapy. The treatment-related toxicities, response rate, 3-year progression-free survival (PFS), and overall survival (OS) were analyzed.ResultsOf 159 patients enrolled between 2014 and 2018, 80 were eligible, including 19 girls and 61 boys, with a median age of 3.9 years (range 0.9–11). After a median follow-up of 24 months (range 3–40), the median OS was 31.8 months, and 3-year OS was 83.8%. In multivariate analyses, the OS was affected by N-MYC amplification (hazard ratio 0.212, 95% confidence interval (CI) 0.049–0.910; p = 0.037) and giant tumor mass (hazard ratio 0.197, 95% CI 0.071–0.552; p = 0.002). The median 3-year PFS was 25.8 months, and 3-year PFS was 57.5%. The univariate analysis showed that only the giant tumor mass was associated with the outcome. Of the 13 deaths, 11 died from the rapid progression of the disease and two from treatment-related toxicities. The most common adverse reaction was chemotherapy-induced hematological toxicity.ConclusionThe PFS and OS reported in our study were similar to Western countries. The CCCG-NB-2014 protocol proved to be an efficient regimen with tolerable side-effect for the treatment of pediatric HR-NB.

Methotrexate Toxicity: Molecular Mechanisms and Management

Methotrexate (MTX) is the most widely used drug in cancer chemotherapy and is considered to be the first-line drug for the treatment of a number of rheumatic and non-rheumatic disorders. The pulmonary toxicity, hepatotoxicity of MTX are two of its major side effects. Other toxicities such as endocrinological toxicity, GI toxicity, cutaneous toxicity, hematological toxicity, fatal malfunction or loss, and malignancy can also occur, but at a significantly lower rate of prevalence. This review aims to provide a comprehensive understanding of the molecular mechanisms of methotrexate toxic effects and Lastly, we discussed the management of this toxicity.