Fatal interstitial pneumonia caused by panitumumab-containing chemotherapy: a case report

A 49-year-old Japanese man visited our institution for the treatment of metastatic rectal cancer. He had no history of interstitial pneumonia or smoking. Although he achieved partial remission with combination chemotherapy consisting of 5-fluorouracil, leucovorin, and oxaliplatin plus bevacizumab, this regimen failed after 46 courses. A salvage chemotherapy consisting of 5-fluorouracil, leucovorin, and irinotecan plus panitumumab was initiated. However, 6 days after treatment initiation, asymptomatic hypoxia was detected. Chest computed tomography revealed interstitial lung disease; therefore, chemotherapy was discontinued and corticosteroid pulse therapy was immediately started. Chest computed tomography on day 20 of the salvage chemotherapy revealed progressive interstitial lesions with lung volume loss and mediastinal emphysema. He passed away a few days later because of respiratory failure. In conclusion, physicians should be aware of the adverse event wherein administration of chemotherapy containing an anti-epidermal growth factor receptor monoclonal antibody might result in a fatal outcome

Importance of cell surface marker to the prognosis of non-Hodgkin's lymphoma.

We studied the correlation between the cell surface markers and prognosis of non-Hodgkin's lymphoma (NHL) patients treated in the Shikoku Cancer Center Hospital from 1980 to 1986. Thirty-one cases were selected on the basis of having a lymphnode as a primary lesion, having been immunophenotyped before chemotherapy, being in the intermediate histologic grade and being in stage II, III or IV. Thirteen cases of the T-cell type (T-lymphomas) and 18 cases of the B-cell type (B-lymphoma) were identified. The complete remission rate was 54% among T-lymphoma patients and 78% among B-lymphoma patients. The median length of survival was 12+ months in T-lymphoma and 26+ months in B-lymphoma. The survival rate of T-lymphoma patients was significantly lower than that of B-lymphoma patients. The importance of making surface marker studies was reappraised in our study.</p

Immunohistochemical detection of P-glycoprotein and carcinoembryonic antigen in small cell lung cancer: with reference to predictability of response to chemotherapy.

In an attempt to elucidate the tumor properties relating to responsiveness to chemotherapy, we examined immunohistochemically the expression of P-glycoprotein (P-gp) and carcinoembryonic antigen (CEA) in small cell lung cancer (SCLC) tumors. Tumor specimens from 33 patients were obtained at the time of diagnosis and relapse. Four patients expressed P-gp in their initial tumors, and 7 others did in recurrent tumors. The overall response rate to chemotherapy of the initial tumors was 75% for P-gp-positive initial tumors and 86% for P-gp-negative tumors, whereas the disease-free and overall survival times were significantly shorter in the former than the latter. Three patients showed CEA in their initial tumors, and 5 others did in recurrent tumors. The patients with CEA-positive initial tumors tended to relapse earlier than those with CEA-negative tumors. In addition, recurrent tumors expressing CEA were resistant to salvage chemotherapy. A clear correlation between CEA expression by tumors and the CEA level in the serum was observed at diagnosis as well as at relapse. These findings indicate that P-gp and/or CEA expression by a tumor and elevated CEA level in the serum may predict refractoriness of the tumor to chemotherapy.</p

Phase II study of ifosfamide, cisplatin, and vindesine combination in advanced non-small cell lung cancer.

Twenty-seven previously untreated patients with unresectable non-small cell lung cancer were treated with a 3-drug combination of ifosfamide, cisplatin, and vindesine as a phase II study. Patients received ifosfamide, 1.3g/m2, on days 1 to 5; cisplatin, 20mg/m2, on days 1 to 5; and vindesine, 3mg/m2, on days 1 and 8; with a sufficient parenteral hydration. Courses were repeated every 4 weeks. Twenty males and seven females with a median age of 61 years were treated and fully evaluated. Five patients had stage IIIA, seven had stage IIIB, and 15 had stage IV disease. One patient with adenocarcinoma achieved a complete response and 16 achieved a partial response, for an overall response rate of 63% (95% confidence limit: 45% to 81%). The median duration of response was 34 weeks (range: 9 to 52 weeks). The median survival time was 58 weeks for patients with IIIA/B disease, and 33 weeks for those with IV disease. The major toxicity was myelosuppression, however, it was generally well-tolerated. These results indicate that the 3-drug combination is active against non-small cell lung cancer and warrants further clinical trials.</p

Mortality and morbidity in two-year disease-free survivors of small cell lung cancer after treatment with combination chemotherapy with or without irradiation.

We evaluated the long-term outcome of 148 patients with small cell lung cancer (SCLC) who had been entered into clinical trials of chemotherapy with or without thoracic and prophylactic cranial irradiation (PCI) between 1981 and 1987. Eighteen patients (12%) survived for 2 or more years. With a minimum follow-up of 4.5 years, 10 of the 18 patients who remained disease-free at 2 years are currently alive and free of SCLC. Seven of these 10 patients currently function as they did before diagnosis. However, three suffer from central nervous system changes of varying degrees in severity which appeared 2-3 years after PCI. Eight of the 18 patients who were disease-free at 2 years have died. Two died of isolated relapse in the brain at 3.6 and 4.2 years after initiation of chemotherapy. Five died of other malignancies while continuing their complete response to SCLC; two of non-small cell lung cancer, two of acute myelogenous leukemia, and one of hepatocellular carcinoma. Another patient died of an unrelated disease without any evidence of SCLC. A small but substantial proportion of patients who underwent intensive treatment will achieve long-term survival; however, these patients remain at higher risk for second cancers and late toxicities. Therefore, attention must be directed to defining the safest way to employ such treatment in the management of SCLC.</p

Novel Urinary Glycan Biomarkers Predict Cardiovascular Events in Patients With Type 2 Diabetes: A Multicenter Prospective Study With 5-Year Follow Up (U-CARE Study 2)

Background: Although various biomarkers predict cardiovascular event (CVE) in patients with diabetes, the relationship of urinary glycan profile with CVE in patients with diabetes remains unclear. Methods: Among 680 patients with type 2 diabetes, we examined the baseline urinary glycan signals binding to 45 lectins with different specificities. Primary outcome was defined as CVE including cardiovascular disease, stroke, and peripheral arterial disease. Results: During approximately a 5-year follow-up period, 62 patients reached the endpoint. Cox proportional hazards analysis revealed that urinary glycan signals binding to two lectins were significantly associated with the outcome after adjustment for known indicators of CVE and for false discovery rate, as well as increased model fitness. Hazard ratios for these lectins (+1 SD for the glycan index) were UDA (recognizing glycan: mixture of Man5 to Man9): 1.78 (95% CI: 1.24-2.55, P = 0.002) and Calsepa [High-Man (Man2-6)]: 1.56 (1.19-2.04, P = 0.001). Common glycan binding to these lectins was high-mannose type of N-glycans. Moreover, adding glycan index for UDA to a model including known confounders improved the outcome prediction [Difference of Harrel's C-index: 0.028 (95% CI: 0.001-0.055, P = 0.044), net reclassification improvement at 5-year risk increased by 0.368 (0.045-0.692, P = 0.026), and the Akaike information criterion and Bayesian information criterion decreased from 725.7 to 716.5, and 761.8 to 757.2, respectively]. Conclusion: The urinary excretion of high-mannose glycan may be a valuable biomarker for improving prediction of CVE in patients with type 2 diabetes, and provides the rationale to explore the mechanism underlying abnormal N-glycosylation occurring in patients with diabetes at higher risk of CVE

Plasma angiotensin-converting enzyme 2 (ACE2) is a marker for renal outcome of diabetic kidney disease (DKD) (U-CARE study 3)

Introduction ACE cleaves angiotensin I (Ang I) to angiotensin II (Ang II) inducing vasoconstriction via Ang II type 1 (AT1) receptor, while ACE2 cleaves Ang II to Ang (1-7) causing vasodilatation by acting on the Mas receptor. In diabetic kidney disease (DKD), it is still unclear whether plasma or urine ACE2 levels predict renal outcomes or not. Research design and methods Among 777 participants with diabetes enrolled in the Urinary biomarker for Continuous And Rapid progression of diabetic nEphropathy study, the 296 patients followed up for 9 years were investigated. Plasma and urinary ACE2 levels were measured by the ELISA. The primary end point was a composite of a decrease of estimated glomerular filtration rate (eGFR) by at least 30% from baseline or initiation of hemodialysis or peritoneal dialysis. The secondary end points were a 30% increase or a 30% decrease in albumin-to-creatinine ratio from baseline to 1 year. Results The cumulative incidence of the renal composite outcome was significantly higher in group 1 with lowest tertile of plasma ACE2 (p=0.040). Group 2 with middle and highest tertile was associated with better renal outcomes in the crude Cox regression model adjusted by age and sex (HR 0.56, 95% CI 0.31 to 0.99, p=0.047). Plasma ACE2 levels demonstrated a significant association with 30% decrease in ACR (OR 1.46, 95% CI 1.044 to 2.035, p=0.027) after adjusting for age, sex, systolic blood pressure, hemoglobin A1c, and eGFR. Conclusions Higher baseline plasma ACE2 levels in DKD were protective for development and progression of albuminuria and associated with fewer renal end points, suggesting plasma ACE2 may be used as a prognosis marker of DKD.Trial registration number UMIN000011525

Chemothrapy of small cell lung cancer : Comparative phase Ⅱ study of CAV-PVP hybrid regimen and CAV-PVP sequential regimen in patients with small cell lung cancer(SCLC)

One hundred and forty three patients with previously untreated SCLC were randomly allocated to receive either the CAV-PVP hybrid (Hyb) regimen or CAV-PVP sequential(Seq) regimen between November 1987 and October 1992. The Hyb regimen consisted of CAV (cyclophosphamide 700mg/㎡,iv,day 1 ; adriamycin 30mg/㎡,iv,day 1 ; and vincristine 1.4mg/㎡,iv,day 1) and PVP (cisplatin 60mg/㎡,iv,day 8 ; and etoposide 100mg/㎡,iv,days 8 and 9), and was repeated up to 6 cycles at 4-week intervals. The Seq regimen consisted of an initial 3 cycles of CAV (cyclophosphamide 700mg/㎡,iv,days 1 and 8 ; adriamycin 30mg/㎡,iv days 1 and 8 ; and vincristine 1.4mg/㎡,iv,day 8 ; and vincristine 1.4mg/㎡,iv days 1 and 8) followed by 3 cycles of PVP (cisplatin 60mg/㎡,iv,days 1 and 8 ; and etoposide 100mg/㎡,iv,days 1, 2, 8 and 9) at 4-week intervals. For patients with limited disease (LD), thoracic irradiation at a dose of 50 Gy was given after a maximal response with chemotherapy, and LD patients achieving a complete response (CR) received prophylactic cranial irradiation at a dose of 30 Gy. For the LD patients, the overall response rate was 97% for the Hyb regimen with a CR rate of 59% and 100% for the Seq regimen with a CR rate of 45%. For the patients with extensive disease (ED), the overall response rate was 94% for the Hyb regimen with a CR rate of 21% and 78% for the Seq regimen with a CR rate of 16%. The median survival time (MST) for the LD patients was 17.9 months for the Hyb group and 20.9 months for the Seq group, and the MST for the ED patients was 9.7 months for the Hyb group and 12.2 months for the Seq group. The 3-year survival rate for the LD patients was 21.9% for the Hyb group and 18.8% for the Seq group. There was a trend favoring the Hyb regimen in terms of overal response rate, CR rate, and 3-year survival rate for the LD patients as well, but there was no significant difference in survival between the two treatment groups. Hematologic toxicity was the major dose-limiting toxicity, but it was generally well-tolerated in both treatment groups. These findings indicate that both Hyb and Seq regimens are equally effective for the prolongation of life in patients with SCLC