Real-world effectiveness of third- or later-line treatment in Japanese patients with HER2-positive, unresectable, recurrent or metastatic gastric cancer: a retrospective observational study.

BACKGROUND: Real-world evidence on the preference for and effectiveness of third- or later-line (3L +) monotherapy for HER2-positive gastric cancer is limited in Japan. This study evaluated the utility of nivolumab, irinotecan, and trifluridine/tipiracil (FTD/TPI) monotherapy as 3L + treatment in Japanese patients with HER2-positive gastric/gastroesophageal junction (G/GEJ) cancer who were previously treated with trastuzumab. METHODS: In this multicenter, retrospective, observational study (20 centers), data of eligible patients were extracted from medical records (September 22, 2017-March 31, 2020), with follow-up until June 30, 2020. Outcomes included overall survival (OS), real-world progression-free survival (rwPFS), time to treatment failure (TTF), objective response rate (ORR; complete response [CR] + partial response [PR]), and disease control rate (DCR). RESULTS: Of 127 enrolled patients, the overall analysis population comprised 117 patients (median [range] age, 71 [38-89] years). The most commonly prescribed 3L + monotherapy was nivolumab (n = 100), followed by irinotecan (n = 12) and FTD/TPI (n = 5). The median (95% confidence interval [CI]) OS, rwPFS, and TTF were 6.2 (4.5-8.0), 1.9 (1.5-2.3), and 1.8 (1.5-2.2) months, respectively, at median (range) 150 (25-1007) days of follow-up. The ORR (CR + PR) and DCR were 9.0% (1% + 8%) and 32.0%, respectively. Factors such as higher neutrophil-lymphocyte ratio (≥ 2.54), Glasgow prognostic score (≥ 1), Eastern Cooperative Oncology Group performance status (ECOG PS; ≥ 2), and hepatic metastasis significantly impacted OS. CONCLUSIONS: The observed OS in this study for HER2-positive G/GEJ cancer was shorter than that reported previously, suggesting that the effectiveness of nivolumab, irinotecan, or FTD/TPI as 3L + therapy may be limited.

Sweat-gland carcinoma with neuroendocrine differentiation (SCAND): a clinicopathologic study of 13 cases with genetic analysis.

Low-grade neuroendocrine carcinoma of the skin (LGNECS) was proposed in 2017 as a new primary cutaneous neoplasm with neuroendocrine differentiation; however, it is not yet well known due to its rarity. Herein, we perform a detailed clinicopathologic analysis of 13 cases as well as panel DNA sequencing in three cases. The study included 12 males and 1 female with a median age of 71 (43-85) years. All lesions occurred on the ventral trunk. The mean tumor size was 2.2 (0.8-11.0) cm. The histopathology resembled that of well-differentiated neuroendocrine tumors (NETs) in other organs, but intraepidermal pagetoid spreading was seen in 8 (61.5%) cases and stromal mucin deposits in 4 (30.8%). Immunoreactivity for CK7, CK19, EMA, BerEP4, CEA, chromogranin A, synaptophysin, INSM1, GCDFP15, GATA3, ER, and bcl-2 were present in varying degrees in all tested cases. PTEN c.165-1G>A splice site mutation was detected by panel sequencing in one case, and GATA3 P409fs*99 and SETD2 R1708fs*4 in another case. Lymph node metastasis was seen significantly in cases with tumor size >2.0 cm [8/8 (100%) vs. 1/5 (20%)]. All three cases with size >3.0 cm were in unresectable advanced-stage [3/3 (100%) vs. 1/10 (10%)], and two of the three patients succumbed to the disease. The two cases of death revealed mild nuclear atypia (mitosis: 1/10 HPFs) and moderate nuclear atypia (2/10 HPFs). Thus, tumor size would be a better prognostic factor than nuclear atypia, mitotic count, and Ki67 index, unlike in NETs. These clinicopathologic and immunohistochemical features would represent the characteristics as skin adnexal tumors with apocrine/eccrine differentiation rather than NETs; therefore, we rename it as sweat-gland carcinoma with neuroendocrine differentiation (SCAND).

Opioid-Induced Constipation in Patients with Cancer Pain in Japan (OIC-J Study): A Post Hoc Analysis.

Opioid-induced constipation (OIC) can limit the clinical benefit of opioid treatment. This post-hoc analysis evaluated the association between the Rome IV diagnostic criteria and other measures for OIC, including the Bowel Function Index (BFI), correlation between demographics and OIC onset, impact of OIC on pain treatment, and impact of patient-healthcare professional (HCP) communication on patient satisfaction. Patients recorded bowel habits in paper diaries for 14 days following opioid initiation. Study-specific questionnaires were used to evaluate patient awareness of OIC and satisfaction. Patients were ≥20 years old, initiating strong opioid therapy for cancer pain, had an ECOG PS ≤ 2, and had no constipation (≥3 bowel movements within 7 days of enrollment). A total of 220 patients were enrolled. The sensitivity and specificity of BFI for identifying OIC were 81.2% and 54.7%, respectively. Age <65 versus ≥65 years (odds ratio (OR) = 0.510, 95% confidence interval (CI): 0.267-0.977) and the presence or absence of comorbidities (OR = 0.443, 95% CI: 0.221-0.885) were correlated with OIC onset. The proportion of inpatients with sustainable pain control at week 2 was similar in patients with or without OIC (60.0% vs. 67.2%, respectively). By patient assessment, there was a significant correlation between an adequate level of patient-HCP communication and satisfaction with OIC treatment (OR = 9.538 (95% CI: 1.577-57.681)). Using BFI to screen for OIC represents a valid approach in patients with cancer pain. Patient-HCP communication is essential for effective management of OIC in patients with cancer pain.

Opioid-induced constipation in patients with cancer pain in Japan (OIC-J study): a post hoc subgroup analysis of patients with gastrointestinal cancer.

BACKGROUND: Constipation is a common side effect of opioid therapy. An observational study of opioid-induced constipation (OIC) in Japanese patients with cancer (OIC-J) included 212 patients with various tumor types. This post hoc analysis of OIC-J evaluated a subgroup of patients with gastrointestinal (GI) cancer. METHODS: Patients were aged ≥ 20 years, starting strong opioid therapy, had an ECOG PS of ≤ 2, and must have had ≥ 3 bowel movements during the week before enrollment. OIC was evaluated for 2 weeks after opioid initiation using the Rome IV diagnostic criteria for colorectal disorders, as well as physician's diagnosis, number of spontaneous bowel movements, Bowel Function Index score, and patient's self-assessment. Relationships between baseline characteristics and OIC incidence, and the effects of OIC on quality of life (QOL) were also explored. RESULTS: Fifty patients from OIC-J who had GI cancer [colon (50%), stomach (28%), and esophageal (22%)] were included. OIC incidence varied by which diagnostic criteria were used (46.0-62.0%) and occurred rapidly after initiating opioid therapy. The use of prophylactic laxatives reduced the overall incidence rate of OIC from 71.0% to 47.4%. No baseline characteristics, except comorbidities, were associated with OIC incidence. Change from baseline to day 15 in PAC-SYM total score was significantly greater for patients with OIC versus those without OIC (0.188 versus -0.362; P = 0.0011). CONCLUSIONS: This post hoc analysis suggests that OIC occurs rapidly in patients with GI cancer after initiating opioid therapy, and negatively impacts QOL. Early and effective intervention strategies may be particularly useful in this group. ADDITIONAL INFORMATION: Coauthor Makio Gamoh is deceased.

Safety and efficacy of cetuximab-containing chemotherapy after immune checkpoint inhibitors for patients with squamous cell carcinoma of the head and neck: a single-center retrospective study.

Immunotherapy has been shown to prolong survival in recurrent or metastatic squamous cell carcinoma of the head and neck (SCCHN) in front-line use; however, subsequent systemic therapy has not been optimized. This study aimed to evaluate the safety and efficacy of cetuximab-containing chemotherapy after immunotherapy. We retrospectively analyzed patients with recurrent or metastatic SCCHN who underwent cetuximab-containing regimens after progression on immunotherapy. Of the 22 patients who met the inclusion criteria, 21 received paclitaxel and cetuximab, and 1 carboplatin and fluorouracil and cetuximab after immunotherapy. Nine patients achieved a partial response, 10 patients had stable disease as their best response on cetuximab-containing chemotherapy, yielding an overall response rate and disease control rate of 40.9 and 86.4%, respectively. The median progression-free survival was 5.2 months, and the median overall survival was 14.5 months. Ten patients developed grade 3-4 adverse events, including neutropenia (31.8%), acneiform rash (9.1%), anemia (4.5%), hypertransaminasemia (4.5%) and stomatitis (4.5%). The most frequent cetuximab-related toxicities across all grades were skin reactions (77.3%), hypomagnesemia (40.9%), stomatitis (27.3%), paronychia (13.6%) and keratitis (4.5%). There was no treatment-related death. Taken together, cetuximab-containing chemotherapy was effective and feasible even after immunotherapy.

Clinical Application of the FoundationOne CDx Assay to Therapeutic Decision-Making for Patients with Advanced Solid Tumors.

BACKGROUND: Implementation of personalized medicine requires the accessibility of tumor molecular profiling in order to allow prioritization of appropriate targeted therapies for individual patients. Our aim was to study the role of comprehensive genomic profiling assays that may inform treatment recommendations for patients with solid tumors. MATERIALS AND METHODS: We performed a prospective study to evaluate the feasibility of application of the FoundationOne CDx panel-which detects substitutions, insertions and deletions, and copy number alterations in 324 genes, select gene rearrangements, and genomic signatures including microsatellite instability and tumor mutation burden (TMB)-to patients with advanced or recurrent solid tumors before its approval in Japan. RESULTS: A total of 181 samples were processed for genomic testing between September 2018 and June 2019, with data being successfully obtained for 175 of these samples, yielding a success rate of 96.7%. The median turnaround time was 41 days (range, 21-126 days). The most common known or likely pathogenic variants were TP53 mutations (n = 113), PIK3CA mutations (n = 33), APC mutations (n = 32), and KRAS mutations (n = 29). Among the 153 patients assessed for TMB, the median TMB was 4 mutations/Mb, and tumors with a high TMB (≥10 mutations/Mb) were more prevalent for lung cancer (11/32) than for other solid tumor types (9/121, Fisher's exact test p < .01). No clear trend toward increased efficacy for immune checkpoint inhibitor (ICI) monotherapy or ICI combination chemotherapy in patients with a high programmed cell death-ligand 1 tumor proportion score or a high TMB was apparent. Among the 174 patients found to harbor known or likely pathogenic actionable alterations, 24 individuals (14%) received matched targeted therapy. CONCLUSION: The FoundationOne CDx assay was performed with formalin-fixed, paraffin-embedded tumor specimens with a success rate of >95%. Such testing may inform the matching of patients with cancer with investigational or approved targeted drugs. IMPLICATIONS FOR PRACTICE: This prospective cohort study was initiated to investigate the feasibility and utility of clinical application of FoundationOne CDx. A total of 181 samples were processed for genomic testing between September 2018 and June 2019, with data being successfully obtained for 175 of these samples, yielding a success rate of 96.7%, and 24 individuals (14%) received matched targeted therapy.

Opioid-induced constipation in patients with cancer pain in Japan (OIC-J study): a post hoc subgroup analysis of patients with lung cancer.

OBJECTIVE: To evaluate the opioid-induced constipation burden in the subgroup of patients with lung cancer who participated in the observational Opioid-Induced Constipation in Patients with Cancer Pain in Japan (OIC-J) study. METHODS: The prospective, observational study, OIC-J, included 212 patients with various tumour types, 33% of whom had lung cancer. The incidence of opioid-induced constipation was evaluated using several diagnostic criteria, as well as the physician's diagnosis and patient's subjective assessment. Following initiation of opioids, patients recorded details of bowel movements (i.e. date/time, Bristol Stool Scale form, sensations of incomplete evacuation or anorectal obstruction/blockage and degree of straining) in a diary for 2 weeks. Relationships between patient characteristics and opioid-induced constipation onset and effects of opioid-induced constipation on quality of life were explored. RESULTS: In total, 69 patients were included in this post hoc analysis. The incidence of opioid-induced constipation varied (39.1-59.1%) depending on which diagnostic criteria was used. Diagnostic criteria that included a quality component or a patient's feeling of bowel movement as an evaluation item (i.e. Rome IV, physician's diagnosis, Bowel Function Index, patient's assessment) showed higher incidences of opioid-induced constipation than recording the number of spontaneous bowel movements alone. Opioid-induced constipation occurred rapidly after initiating opioids and had a significant impact on Patient Assessment of Constipation Symptoms total score (P = 0.0031). Patient baseline characteristics did not appear to be predictive of opioid-induced constipation onset. CONCLUSIONS: In patients with lung cancer, opioid-induced constipation can occur quickly after initiating opioids and can negatively impact quality of life. Early management of opioid-induced constipation, with a focus on quality-of-life improvement and patient's assessments of bowel movements, is important for these patients.

Glasgow Prognostic Score (GPS) and Tumor Response as Biomarkers of Nivolumab Monotherapy in Third- or Later-line Setting for Advanced Gastric Cancer.

BACKGROUND/AIM: This study aimed to seek clinical biomarkers of nivolumab monotherapy for advanced gastric cancer (AGC) of which efficacy is limited. We focused on Glasgow Prognostic Score (GPS), which reflects systemic inflammatory and nutritional status as well as disease control by chemotherapy immediately before nivolumab (DCBC). PATIENTS AND METHODS: AGC patients with measurable lesions who were treated with nivolumab in the third- or later-line were included. DCBC was defined as a best overall response of complete response (CR), partial response, stable disease, or non-CR/non-progressive disease achieved by chemotherapy immediately before nivolumab. RESULTS: Eighty patients were analyzed. Among the various clinical factors, multivariable analysis revealed that a GPS of 2 was significantly associated with a shorter overall survival and DCBC was significantly associated with a longer progression-free survival. CONCLUSION: We present the potential of GPS and DCBC as efficient biomarkers of nivolumab for AGC, that warrants further evaluation.

A Case of Pathological Complete Response Following FOLFIRINOX Therapy for Pancreatic Adenocarcinoma with Synchronous Distant Lymph Node Metastases.

INTRODUCTION: We report a case of conversion surgery for pancreatic ductal adenocarcinoma (PDAC) with synchronous distant metastases showing pathological complete response (pCR) after FOLFIRINOX therapy. PRESENTATION OF CASE: A 46-year-old woman with obstructive jaundice was referred to our hospital. A CT scan revealed a hypo-vascular mass in the head of the pancreas with multiple para-aortic lymph nodes and a Virchow's node swollen. The serum CA 19-9 level was 71795.1 U/mL. The result of tumor biopsy from the biliary stenotic site was concordant with adenocarcinoma. She was diagnosed with PDAC with distant metastases. After 10 courses of FOLFIRINOX followed by 4 courses of FOLFIRI, a CT scan showed that distant lymph node swellings disappeared, and CA19-9 level became almost normal. She underwent pancreaticoduodenectomy with dissection of para-aortic lymph nodes 8 months after the initiation of chemotherapy. Pathologically, no evidence of residual adenocarcinoma was observed in neither pancreas nor lymph nodes. Adjuvant chemotherapy using S-1 was administered for 6 months, and no recurrence has been observed 4 years after surgery. BRCA1/2 mutations were not detected in patient's DNA. DISCUSSION: With the induction of intensive chemotherapies such as FOLFIRINOX, an increasing number of patients with synchronous distant metastases could become suitable candidates for surgery of the primary lesion because of the potential complete response of metastatic lesions. CONCLUSION: This case presented a rare occurrence of pCR in a patient with unresectable PDAC with distant metastases who received FOLFIRINOX. The feasibility and benefits of conversion surgery in such patients must be investigated in future trials.

Patients' Self-Assessment of the Symptoms and Impact of Opioid-Induced Constipation: Results From a Prospective Observational Cohort Study of Japanese Patients With Cancer.

CONTEXT: Many patients who have cancer consider opioid-induced constipation (OIC) to be a burdensome side effect of opioid treatment. OBJECTIVES: To evaluate patient-reported outcomes in Japanese patients with cancer pain and OIC. METHODS: This prospective observational study evaluated OIC incidence for two weeks in patients with cancer after they initiated strong opioid therapy. Rome IV diagnostic criteria, a physician's diagnosis, spontaneous bowel movements, Bowel Function Index score, and patients' daily self-assessments were used. Changes from baseline in Patient Assessment of Constipation Symptoms and Patient Assessment of Constipation Quality of Life (PAC-QOL) scores were compared between patients with and without OIC. Patients and health care providers (HCPs) completed study-specific questionnaires regarding OIC burden, treatment satisfaction, and patient-provider communications. RESULTS: Among 212 enrolled patients, the incidence of OIC was 47.6% by patients' self-assessments, with a cumulative incidence of 30.2% by Day 3 and 43.5% by Day 7. Patient Assessment of Constipation Symptoms and PAC-QOL overall scores from patients with OIC worsened significantly from baseline compared with patients without OIC by all diagnostic criteria, except for spontaneous bowel movement frequency for PAC-QOL. Patients and HCPs were generally satisfied with OIC treatment; however, 53.5% of patients and approximately 40.0% of HCPs reported that OIC affected pain management. Most patients and HCPs reported that OIC conditions were sufficiently or essentially communicated. CONCLUSION: After starting opioid therapy, patients recognized OIC onset and its impact on cancer pain management, highlighting the need for effective patient-provider communications, diagnosis, and treatment of OIC to improve QOL for patients with cancer receiving opioid analgesics.

[Outcomes of FOLFIRINOX as First-Line Treatment for Recurrent or Unresectable Pancreatic Cancer].

We retrospectively analyzed adverse effects(AEs), overall survival(OS), and progression-free survival(PFS)in 15 consecutive patients treated with FOLFIRINOX as the first-line treatment for recurrent or unresectable pancreatic ductal adenocarcinoma( PDAC)between February 2014 and December 2017 in our hospital. Eleven patients were treated for unresectable PDAC with distant metastases(UR-M), and 4 were treated for locally advanced unresectable PDAC(UR-LA). The median age was 56(range: 40-75)years. Nine patients were male, and 6 were female. The performance status was 0 or 1 in all patients. Tumors were located in the pancreas head in 8 cases and in the body-tail in 7 cases. Grade 5 AEs were observed in 1 case in which liver abscess causing sepsis resulted in mortality. The response rate was 20.0%, and the disease control rate was 66.7%. Two patients underwent conversion surgery after FOLFIRINOX treatment. Seven patients received a nab-paclitaxel plus gemcitabine regimen as second-line treatment. The median OS and PFS were 17.0 and 8.4 months, respectively, and the 1-year survival rate was 66.7%. FOLFIRINOX for recurrent and unresectable PDAC showed relatively good tumor control. However, strict attention is required for severe AEs. Conversion surgery might be effective in patients who are good responders even if they have metastatic disease.

Incidence of opioid-induced constipation in Japanese patients with cancer pain: A prospective observational cohort study.

This multicenter, prospective, observational cohort study assessed opioid induced constipation (OIC) in Japanese patients with cancer. Eligible patients had stable cancer and an ECOG PS of 0-2. OIC incidence based on the Rome IV diagnostic criteria was determined by patient diary entries during the first 14 days of opioid therapy. The proportion of patients with OIC was calculated for each 1-week period and the overall 2-week study period. Secondary measurements of OIC included the Bowel Function Index (BFI) score (patient assessment administered by physician), spontaneous bowel movements (SBMs) per week (patient assessment), and physician assessments. Medication for constipation was allowed. Two hundred and twenty patients were enrolled. The mean morphine-equivalent dose was 22 mg/day. By Rome IV criteria, the cumulative incidence of OIC was 56% (95% CI: 49.2%-62.9%); week 1, 48% (95% CI: 40.8%-54.6%); week 2, 37% (95% CI: 30.1%-43.9%). The cumulative incidence of OIC was lower in patients who received prophylactic agents for constipation (48% [95% CI: 38.1%-57.5%]) than in patients who did not (65% [95% CI: 55.0%-74.2%]). The cumulative incidences of OIC were 59% (95% CI: 51.9%-66.0%), 61% (95% CI: 54.3%-68.1%), and 45% (95% CI: 38.0%-51.8%) based on BFI scores, physician assessments, and SBM frequency, respectively. Frequency of BMs/week before starting opioids was the most influential factor for the occurrence of OIC. Utilization of prophylactic agents for constipation was associated with a modest effect on reducing the incidence of OIC. The incidences of OIC reported were variable depending on the diagnostic tool involved.

Retrospective study of unplanned hospital admission for metastatic cancer patients visiting the emergency department.

PURPOSE: The purpose of the study was to identify factors that predict unplanned admission for metastatic cancer patients visiting the emergency department (ED). METHODS: Patients visiting the ED of a general hospital from April 2012 to March 2013 were investigated retrospectively. Data including demographics, vital signs, and laboratory measurements were collected from a chart review for each patient. Factors related to emergency admission were identified by univariate and multivariate analyses. RESULTS: A total of 15,716 individuals visiting the ED during the study period included 1244 (7.9%) patients with cancer. Among the 491 cancer patients with metastasis, univariate analysis revealed that emergency admission was significantly associated with an age of ≥76 years; an altered mental status; fever (≥38 °C); a blood oxygen saturation of <90%; a white blood cell (WBC) count of ≤2000 or ≥10,000/µL; hypoalbuminemia (≤2.5 g/dL); and elevated levels of aspartate aminotransferase (≥100 IU/L), blood urea nitrogen (≥25 mg/dL), and C-reactive protein (CRP, ≥10 mg/dL). Multivariate analysis identified age, an altered mental status, hypoxemia, an abnormal WBC count, and elevated CRP as putative independent predictive factors for emergency admission. The number of these five factors present was also correlated with 30-day mortality (c-statistic = 0.72). CONCLUSIONS: Age, unconsciousness, hypoxemia, an abnormal WBC count, and elevated CRP were found to be associated with emergency admission and 30-day mortality for metastatic cancer patients. Prospective validation of a predictive scoring system based on these findings is warranted.

Chronic nicotine exposure mediates resistance to EGFR-TKI in EGFR-mutated lung cancer via an EGFR signal.

BACKGROUND: Some of patients with non-small cell lung cancer (NSCLC) harboring somatic activating mutations of the epidermal growth factor receptor gene (EGFR mutations) show poor responses to EGFR-tyrosine kinase inhibitors (EGFR-TKIs) treatment. Cigarette smoking is the strongest documented risk factor for the development of lung cancer. Nicotine, while not carcinogenic by itself, has been shown to induce proliferation, angiogenesis, and the epithelial-mesenchymal transition; these effects might be associated with EGFR-TKI resistance. MATERIALS AND METHODS: PC-9 and 11_18 cell lines (EGFR-mutated NSCLC cell lines) were cultured with 1µM nicotine for 3 months and were designated as PC-9/N and 11_18/N cell lines, respectively. The sensitivities of these cell lines to EGFR-TKI were then tested in vitro. Moreover, the association between the smoking status and the progression-free survival (PFS) period was investigated in patients with EGFR-mutated NSCLC who were treated with gefitinib. RESULTS: The PC-9/N and 11_18/N cell lines were resistant to EGFR-TKI, compared with controls. The phosphorylation of EGFR in these cell lines was reduced by EGFR-TKI to a smaller extent than that observed in controls, and a higher concentration of EGFR-TKI was capable of further decreasing the phosphorylation. Clinically, smoking history was an independent predictor of a poor PFS period on gefitinib treatment. CONCLUSIONS: Chronic nicotine exposure because of cigarette smoking mediates resistance to EGFR-TKI via an EGFR signal. Smoking cessation is of great importance, while resistance may be overcome through the administration of high-dose EGFR-TKI.

Feasibility study of two schedules of sunitinib in combination with pemetrexed in patients with advanced solid tumors.

BACKGROUND: Sunitinib is an oral multitargeted tyrosine kinase inhibitor of vascular endothelial growth factor and platelet-derived growth factor receptors, as well as of other receptor types. We have performed a feasibility study to investigate the safety of sunitinib in combination with pemetrexed for treatment of advanced refractory solid tumors. METHODS: Sunitinib was administered once daily on a continuous daily dosing (CDD) schedule (37.5 mg/day) or a 2-weeks-on, 1-week-off treatment schedule (50 mg/day, Schedule 2/1) in combination with pemetrexed at 500 mg/m(2) on day 1 of repeated 21-day cycles. RESULTS: Twelve patients were enrolled in the study: six on the CDD schedule and six on Schedule 2/1. None of the treated patients experienced a dose-limiting toxicity. Toxicities were manageable and similar in type to those observed in monotherapy studies of sunitinib and pemetrexed. Pharmacokinetic analysis did not reveal any substantial drug-drug interaction. One patient with squamous cell lung cancer showed a partial response and five patients had stable disease. CONCLUSIONS: Combination therapy with sunitinib administered on Schedule 2/1 (50 mg/day) or a CDD schedule (37.5 mg/day) together with standard-dose pemetrexed (500 mg/m(2)) was well tolerated in previously treated patients with advanced solid tumors.

High-dose dexamethasone plus antihistamine prevents colorectal cancer patients treated with modified FOLFOX6 from hypersensitivity reactions induced by oxaliplatin.

BACKGROUND: Oxaliplatin is a third-generation platinum compound and a key agent for the management of colorectal cancer. Patients treated with oxaliplatin are at risk for hypersensitivity reactions. We designed a modified premedication regimen to prevent oxaliplatin-related hypersensitivity reactions and assessed if this approach is effective. METHODS: A retrospective cohort study of patients with advanced colorectal cancer who received modified FOLFOX6 (mFOLFOX6) was performed. Patients received routine premedication with dexamethasone 8 mg and granisetron 3 mg for the first five cycles of mFOLFOX6. From the sixth cycle onward, cohort 1 received the same premedication, and cohort 2 received modified premedication (diphenhydramine 50 mg orally, followed by dexamethasone 20 mg, granisetron 3 mg, and famotidine 20 mg). We compared the incidence of hypersensitivity reactions, duration of treatment, and reasons for treatment withdrawal between the two cohorts. RESULTS: A total of 181 patients were studied (cohort 1, 81; cohort 2, 100). Hypersensitivity reactions developed in 16 patients (20%) in cohort 1 and 7 (7.0%) in cohort 2 (P = 0.0153). The median number of cycles increased from 9 in cohort 1 to 12 in cohort 2. Apart from progressive disease, neurotoxicity was the reason for discontinuing treatment in 20% of the patients in cohort 1, as compared with 53% in cohort 2. CONCLUSION: Increased doses of dexamethasone and antihistamine significantly reduced oxaliplatin-related hypersensitivity reactions. This effective approach should be considered for all patients who receive FOLFOX, allowing treatment to be completed as planned.

Left atrial extension of metastatic lung tumor via pulmonary vein: report on the first case of Ewing sarcoma.

Extension of metastatic lung tumors into the left atrium via pulmonary veins is rare. Here, we report the first case of Ewing sarcoma exhibiting such extension. A 31-year-old man with pulmonary metastasis from Ewing sarcoma presented with a mass in the left lung, extending to the left atrium through the left inferior pulmonary vein. As the patient was considered to be at risk of tumor embolism, the mass was excised surgically.