Potential Diagnostic Value of Salivary Tumor Markers in Breast, Lung and Ovarian Cancer: A Preliminary Study.

The aim of the study was to determine the content of tumor markers for breast, lung and ovarian cancer in saliva, as well as for benign diseases of the corresponding organs and in the control group, and to evaluate their diagnostic significance. Strictly before the start of treatment, saliva samples were obtained and the concentrations of tumor markers (AFP, NSE, HE4, CA15-3, CA72-4, CA125 and CEA) were determined using an enzyme immunoassay (ELISA). CA125 and HE4 were simultaneously determined to be in the blood serum of patients with ovarian cancer. The concentrations of salivary CEA, NSE, CA15-3, CA72-4 and CA125 of the control group were significantly lower than in oncological diseases; however, these tumor markers also increased in saliva with benign diseases. The content of tumor markers depends on the stage of cancer, and the presence of lymph node metastasis; however, the identified patterns are statistically unreliable. The determination of HE4 and AFP in saliva was not informative. In general, the area of potential use of tumor markers in saliva is extremely narrow. Thus, CEA may be diagnostic for breast and lung cancer, but not for ovarian cancer. CA72-4 is most informative for ovarian mucinous carcinoma. None of the markers showed significant differences between malignant and non-malignant pathologies.

A Phase II Randomized, Double-Blind, Placebo-Controlled Study of Simtuzumab or Placebo in Combination with Gemcitabine for the First-Line Treatment of Pancreatic Adenocarcinoma.

LESSONS LEARNED: The safety profile in the gemcitabine/simtuzumab group was similar to that in the gemcitabine/placebo group.The addition of simtuzumab to gemcitabine does not improve clinical outcomes in patients with metastatic pancreatic adenocarcinoma ABSTRACT: Background.The humanized IgG4 monoclonal antibody simtuzumab inhibits the extracellular matrix-remodeling enzyme lysyl oxidase-like 2 maintaining pathological stroma in tumors. METHODS: Adult patients with metastatic pancreatic adenocarcinoma (mPaCa) were randomly assigned to receive intravenous gemcitabine, 1,000 mg/m2, in combination with 200 or 700 mg simtuzumab or placebo. Primary endpoint was progression-free survival (PFS), secondary endpoints included overall survival (OS), objective response rate (ORR), and safety. RESULTS: Of 240 patients, 80 were randomly assigned to gemcitabine/simtuzumab 700 mg, 79 to gemcitabine/simtuzumab 200 mg, and 81 to gemcitabine/placebo. After a median follow-up of 3.0, 1.9, and 3.4 months for gemcitabine/simtuzumab 700 mg, gemcitabine/simtuzumab 200 mg, and gemcitabine/placebo, respectively, the median PFS was 3.7 months (adjusted hazard ratio [HR], 95% confidence interval [CI], p value vs placebo: 1.09 [0.74-1.61]; p = .73), 3.5 months (1.13 [0.76-1.66], p = .61]), and 3.7 months, respectively. Median OS was 7.6 months (0.83 [0.57-1.22]; p = .28), 5.9 months (1.07 [0.73-1.55]; p = .69), and 5.7 months, respectively. ORRs were 13.9%, 14.5%, and 23.5%, respectively. Simtuzumab was well tolerated. CONCLUSION: The addition of simtuzumab to gemcitabine did not improve clinical outcomes in patients with mPaCa. The Oncologist 2017;22:241-e7.

A Phase II, Randomized, Double-Blind, Placebo-Controlled Study of Simtuzumab in Combination with FOLFIRI for the Second-Line Treatment of Metastatic KRAS Mutant Colorectal Adenocarcinoma.

LESSONS LEARNED: The safety profile in the patient groups who received FOLFIRI and simtuzumab did not differ from that in the FOLFIRI and placebo group.The addition of simtuzumab to chemotherapy with FOLFIRI does not improve clinical outcomes in patients with metastatic KRAS mutant colorectal carcinoma. BACKGROUND: Simtuzumab, a humanized IgG4 monoclonal antibody to lysyl oxidase-like 2 (LOXL2), blocks desmoplastic reaction in colorectal carcinoma (CRC) cells in vitro. METHODS: Patients with metastatic Kirsten rat sarcoma viral oncogene homolog (KRAS) mutant CRC were randomized to receive second-line 5-fluorouracil, leucovorin, and irinotecan (FOLFIRI) with either 200 or 700 mg simtuzumab or placebo every 2 weeks in cycles of 28 days. Progression-free survival (PFS), overall survival (OS), objective response rate (ORR), and safety were assessed. RESULTS: In total, 249 patients were randomized and treated with FOLFIRI/simtuzumab 700 mg (n = 84), FOLFIRI/simtuzumab 200 mg (n = 85), and FOLFIRI/placebo (n = 80). After a median follow-up of 5.1, 3.8, and 5.5 months, respectively, median PFS for each of the respective treatment groups was 5.5 months (adjusted HR [95% CI], p value versus placebo; 1.32 [0.92, 1.89]; p = .10), 5.4 months (1.45 [1.01, 2.06]; p = .04), and 5.8 months. Median OS was 11.4 months (1.23 [0.80, 1.91]; p = .25), 10.5 months (1.50 [0.98, 2.30]; p = .06), and 16.3 months, respectively. ORR was 11.9%, 5.9%, and 10%, respectively. Simtuzumab was tolerable in metastatic KRAS mutant CRC patients. CONCLUSION: The addition of simtuzumab to FOLFIRI did not improve clinical outcomes in patients with metastatic KRAS mutant CRC. The Oncologist 2017;22:243-e8.