Abstract OT3-02-06: A phase 1 study of BMN 673 in combination with carboplatin and paclitaxel in patients with advanced solid tumors (NCI9782)

Background: Poly(ADP-ribose) polymerase (PARP) enzymes are involved in DNA repair and are activated by DNA strand breaks. DNA damage from carboplatin has been associated with activation of PARP. Preclinical data indicate that PARP inhibition potentiates the anti-tumor effect of platinum chemotherapy. BMN 673 (Talazoparib) is an oral, selective PARP inhibitor. The phase I single agent maximum tolerated dose (MTD) of BMN 673 given once daily was 1mg po qd. Myelosuppresion was primary dose-limiting toxicity (DLT), including grade 3-4 thrombocytopenia. Carboplatin with paclitaxel is a current standard treatment for many solid tumors, including ovarian, bladder, upper gastrointestinal, breast and non-small cell lung cancer. Myelosuppression, including thrombocytopenia, is also seen with this combination. This phase 1 study is combining BMN 673 with carboplatin once every 3 weeks and weekly paclitaxel.Trial Design: Two dosing schedules are being investigated. In both schedules intravenous carboplatin will be administered on day 1 and paclitaxel on days 1, 8, 15 of a 21-day cycle. BMN 673 will be dosed orally once daily for days 1-7 (schedule A) or days 1-3 (schedule B) starting on day 1 of each cycle. After 4-6 cycles of the combination therapy, subjects may continue the combination, change to carboplatin and intermittent BMN 673 without paclitaxel or change to BMN 673 alone with continuous daily dosing. Each schedule will have a 6 subject dose expansion at the MTD. The starting do...
Source: Cancer Research - Category: Cancer & Oncology Authors: Tags: Ongoing Clinical Trials Source Type: research

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We describe a unique, complex case of a man resulted affected by both APS-2 and MEN-2a. The patient developed Hashimoto's thyroiditis, diabetes mellitus type 1 and AAD, despite testing negative for adrenal cortex autoantibodies (ACA) and steroid 21-hydroxylase autoantibodies (21-OHAb). Moreover, he had also a family history for MEN-2a and he first developed medullay thyroid cancer, then bilateral pheochromocytoma on the adrenal substrate of an AAD. On adrenal histology we found complete bilateral cortical atrophy in the presence of a lymphocytic infiltration and fibrosis, confirming an ACA and 21-OHAb-negative AAD. This da...
Source: Endocrine Journal - Category: Endocrinology Tags: Endocr J Source Type: research
CONCLUSIONS: The ATA risk stratification system is a reliable predictor of short-term outcomes in patients with DTC in real-world clinical settings characterized by center heterogeneity in terms of size, location, level of care, local management strategies, and resource availability. PMID: 32475305 [PubMed - as supplied by publisher]
Source: Thyroid : official journal of the American Thyroid Association - Category: Endocrinology Tags: Thyroid Source Type: research
Source: World Journal of Surgery - Category: Surgery Source Type: research
Source: World Journal of Surgery - Category: Surgery Source Type: research
Authors: Zamanian-Daryoush M, Lindner DJ, Buffa J, Gopalan B, Na J, Hazen SL, DiDonato JA Abstract Previously, we reported apolipoprotein A-I (apoA-I), the major protein component of high-density lipoprotein (HDL), has potent anti-melanoma activity. We used DNA microarray and bioinformatics to interrogate gene expression profiles of tumors from apoA-I expressing (A-I Tg+/-) versus apoA-I-null (A-I KO) animals to gain insights into mechanisms of apoA-I tumor protection. Differential expression analyses of 11 distinct tumors per group with> 1.2-fold cut-off and a false discovery rate adjusted p
Source: Oncotarget - Category: Cancer & Oncology Tags: Oncotarget Source Type: research
Authors: Miranti CK, Moore S, Kim Y, Chappeta VR, Wu K, De B, Gokhale V, Hurley LH, Reyes-Reyes EM Abstract The androgen receptor (AR) is a major driver of prostate cancer development and progression. Men who develop advanced prostate cancer often have long-term cancer control when treated with androgen-deprivation therapies (ADT). Still, their disease inevitably becomes resistant to ADT and progresses to castration-resistant prostate cancer (CRPC). ADT involves potent competitive AR antagonists and androgen synthesis inhibitors. Resistance to these types of treatments emerges, primarily through the maintenance of ...
Source: Oncotarget - Category: Cancer & Oncology Tags: Oncotarget Source Type: research
CONCLUSIONS: Expression of PD-1 and PD-L1 in gastric cancer lymph nodes was demonstrated for the first time. PD-1 is expressed in positive and negative nodes, which could activate the PD-1 pathway. Lymphocytes from tumor-free lymph nodes were negative for PD-L1, and this might represent an advantage for selecting these lymph nodes as a potential source of immune cells for adoptive immunotherapy. PMID: 32477462 [PubMed]
Source: Oncotarget - Category: Cancer & Oncology Tags: Oncotarget Source Type: research
Authors: Gomes I, de Almeida BP, Dâmaso S, Mansinho A, Correia I, Henriques S, Cruz-Duarte R, Vilhais G, Félix P, Alves P, Corredeira P, Barbosa-Morais NL, Costa L, Casimiro S Abstract The role of RANKL-RANK pathway in progesterone-driven mammary carcinogenesis and triple negative breast cancer tumorigenesis has been well characterized. However, and despite evidences of the existence of RANK-positive hormone receptor (HR)-positive breast tumors, the implication of RANK expression in HR-positive breast cancers has not been addressed before. Here, we report that RANK pathway affects the expression of cel...
Source: Oncotarget - Category: Cancer & Oncology Tags: Oncotarget Source Type: research
CONCLUSIONS: Platelet count, a marker of vascular repair capability, appears to modify the relationship between handgrip strength and CMBs. PMID: 32477460 [PubMed]
Source: Oncotarget - Category: Cancer & Oncology Tags: Oncotarget Source Type: research
Authors: Kapoor V, Collins A, Griffith K, Ghosh S, Wong N, Wang X, Challen GA, Krambs J, Link D, Hallahan DE, Thotala D Abstract The immune system plays a vital role in cancer therapy, especially with the advent of immunotherapy. Radiation therapy induces iatrogenic immunosuppression referred to as radiation-induced lymphopenia (RIL). RIL correlates with significant decreases in the overall survival of cancer patients. Although the etiology and severity of lymphopenia are known, the mechanism(s) of RIL are largely unknown. We found that irradiation not only had direct effects on circulating lymphocytes but also had...
Source: Oncotarget - Category: Cancer & Oncology Tags: Oncotarget Source Type: research
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