Deep and ongoing response of castrate-resistant prostate cancer on very low-dose enzalutamide in an elderly chemotherapy –naïve patient: a case report
ConclusionLow doses of enzalutamide may be efficacious, while also reducing the risk of side effects. Furthermore, employing a lower dose would reduce healthcare costs and increase access to enzalutamide. Studies exploring the efficacy of lower enzalutamide doses are warranted. (Source: Cancer Chemotherapy and Pharmacology)
Source: Cancer Chemotherapy and Pharmacology - April 4, 2021 Category: Cancer & Oncology Source Type: research

Clinical pharmacology strategies in supporting drug development and approval of antibody –drug conjugates in oncology
AbstractAntibody –drug conjugates (ADCs) are important molecular entities in the treatment of cancer. These conjugates combine the target specificity of monoclonal antibodies with the potent anti-cancer activity of small-molecule therapeutics. The complex structure of ADCs poses unique challenges to characterize t he drug’s pharmacokinetics (PKs) and pharmacodynamics (PDs) since it requires a quantitative understanding of the PK and PD properties of multiple different molecular species (e.g., ADC conjugate, total antibody and unconjugated cytotoxic drug). As a result, clinical pharmacology strategy of an AD C is rather...
Source: Cancer Chemotherapy and Pharmacology - April 1, 2021 Category: Cancer & Oncology Source Type: research

Switching from zoledronic acid to denosumab increases the risk for developing medication-related osteonecrosis of the jaw in patients with bone metastases
ConclusionOur results suggest that switching from ZA to denosumab significantly increases the risk for developing MRONJ in patients with bone metastases. (Source: Cancer Chemotherapy and Pharmacology)
Source: Cancer Chemotherapy and Pharmacology - March 31, 2021 Category: Cancer & Oncology Source Type: research

Changes in expression of lysosomal membrane proteins in leucocytes of cancer patients treated with tyrosine kinase inhibitors
Conclusion: prolonged treatment of cancer patients with SUN and IM did not induce leucocyte lysosomal biogenesis but dramatically  affected expression of ATP6V1B2. (Source: Cancer Chemotherapy and Pharmacology)
Source: Cancer Chemotherapy and Pharmacology - March 30, 2021 Category: Cancer & Oncology Source Type: research

The pharmacokinetics of pamiparib in the presence of a strong CYP3A inhibitor (itraconazole) and strong CYP3A inducer (rifampin) in patients with solid tumors: an open-label, parallel-group phase 1 study
ConclusionsPamiparib plasma exposure was reduced 38 –43% with rifampin coadministration but was unaffected by itraconazole coadministration. Pamiparib dose modifications are not considered necessary when coadministered with CYP3A inhibitors. Clinical safety and efficacy data will be used with these results to recommend dose modifications when pamip arib is coadministered with CYP3A inducers. (Source: Cancer Chemotherapy and Pharmacology)
Source: Cancer Chemotherapy and Pharmacology - March 27, 2021 Category: Cancer & Oncology Source Type: research

Selinexor population pharmacokinetic and exposure –response analyses to support dose optimization in patients with diffuse large B-cell lymphoma
ConclusionsSimulations of the safety and efficacy ER models suggested that, compared to a starting dose of 60  mg twice weekly (BIW), a 40 mg BIW regimen resulted in an absolute decrease in AE probabilities between 1.9 and 5.3%, with a clinically significant absolute efficacy decrease of 4.7% in ORR. The modeling results support that 60 mg BIW is the optimal dose in patients with DLBCL. (Source: Cancer Chemotherapy and Pharmacology)
Source: Cancer Chemotherapy and Pharmacology - March 26, 2021 Category: Cancer & Oncology Source Type: research

Oral recombinant methioninase combined with paclitaxel arrests recalcitrant ovarian clear cell carcinoma growth in a patient-derived orthotopic xenograft (PDOX) nude-mouse model
ConclusionPTX plus o-rMETase arrested the OCCC tumor growth. o-rMETase is readily administered and can greatly enhance first-line therapy of a recalcitrant cancer. The novel and effective treatment strategy in the present report has future clinical potential for patients with OCCC, especially for patients who cannot well tolerate platinum-based therapy. (Source: Cancer Chemotherapy and Pharmacology)
Source: Cancer Chemotherapy and Pharmacology - March 25, 2021 Category: Cancer & Oncology Source Type: research

Renal toxicity of targeted therapies for renal cell carcinoma in patients with normal and impaired kidney function
AbstractThe introduction of novel targeted therapies during the last 2 decades has led to a significant improvement in patients' clinical outcomes with renal cell carcinoma. However, this improvement came at the price of a whole new spectrum of adverse events, including renal toxicity. Systemic treatment of patients with kidney neoplasms who often present with impairment of kidney function, even prior to treatment, poses an increasing diagnostic and therapeutic challenge for clinicians. Common lifestyle-related comorbidities, i.e., hypertension and diabetes, may contribute to further impairment of kidney function. The lack...
Source: Cancer Chemotherapy and Pharmacology - March 25, 2021 Category: Cancer & Oncology Source Type: research

Pharmacogenomics and functional imaging to predict irinotecan pharmacokinetics and pharmacodynamics: the predict IR study
ConclusionsExploratory associations were observed between Irinotecan PK/PD with hepatic functional imaging and extensive pharmacogenomics. Further work is required to confirm and validate these findings in a larger cohort of patients.Australian New Zealand Clinical Trials Registry (ANZCTR) NumberACTRN12610000897066, Date registered: 21/10/2010. (Source: Cancer Chemotherapy and Pharmacology)
Source: Cancer Chemotherapy and Pharmacology - March 23, 2021 Category: Cancer & Oncology Source Type: research

Dynamics of leucocyte DNA thioguanine nucleotide levels during maintenance therapy of childhood acute lymphoblastic leukemia
ConclusionFluctuations in DNA-TGTotal are predominantly caused by corresponding fluctuations in DNA-TGPMN, thus DNA-TGTotal measures recent TGN incorporation in these short-lived cells. Measurement of DNA-TGTotal at 2 –4 weeks intervals provides a reliable profile of DNA-TG levels. (Source: Cancer Chemotherapy and Pharmacology)
Source: Cancer Chemotherapy and Pharmacology - March 23, 2021 Category: Cancer & Oncology Source Type: research

Niraparib with androgen receptor-axis-targeted therapy in patients with metastatic castration-resistant prostate cancer: safety and pharmacokinetic results from a phase 1b study (BEDIVERE)
ConclusionsThese results support the choice of niraparib 200  mg as the RP2D with AAP. The niraparib–AAP combination was tolerable in patients with mCRPC, with no new safety signals. An ongoing phase 3 study is further assessing this combination in patients with mCRPC.Trial registration no.NCT02924766 (ClinicalTrials.gov). (Source: Cancer Chemotherapy and Pharmacology)
Source: Cancer Chemotherapy and Pharmacology - March 22, 2021 Category: Cancer & Oncology Source Type: research

Pharmacokinetics of docetaxel and ritonavir after oral administration of ModraDoc006/r in patients with prostate cancer versus patients with other advanced solid tumours
ConclusionThe exposure to docetaxel and ritonavir was significantly lower in prostate cancer patients as compared to patients with other types of solid tumours, treated on ModraDoc006/r 30 –20/100–100. An increase of the ritonavir dose increased the docetaxel exposure in mCRPC patients. Therefore, a different RP2D of ModraDoc006/r is pursued in castrated prostate cancer patients as compared to patients with other types of solid tumours.Trial registrationStudy 1: ClinicalTrials.gov Identifier NCT01173913, date of registration August 2, 2010. Study 2: ClinicalTrials.gov Identifier NCT03066154, date of registration Februa...
Source: Cancer Chemotherapy and Pharmacology - March 20, 2021 Category: Cancer & Oncology Source Type: research

Anticancer potential of metformin: focusing on gastrointestinal cancers
AbstractGastrointestinal cancers are one of the most common types of cancer that have high annual mortality; therefore, identification and introduction of safe drugs in the control and prevention of these cancers are of particular importance. Metformin, a lipophilic biguanide, is the most commonly prescribed agent for type 2 diabetes management. In addition to its great effects on lowering the blood glucose concentrations, the anti-cancer properties of this drug have been reported in many types of cancers such as gastrointestinal cancers. Hence the effects of this agent as a safe drug on the reduction of gastrointestinal c...
Source: Cancer Chemotherapy and Pharmacology - March 20, 2021 Category: Cancer & Oncology Source Type: research

Clinical utility of ABCB1 and ABCG2 genotyping for assessing the clinical and pathological response to FAC therapy in Mexican breast cancer patients
ConclusionThe early clinical response and its association with SNPs in the ABCB1 transporter are preserved until the pathological response to neoadjuvant chemotherapy; therefore, it could be used as a predictor of chemoresistance in locally advanced  breast cancer patients of the Mexican population. (Source: Cancer Chemotherapy and Pharmacology)
Source: Cancer Chemotherapy and Pharmacology - March 19, 2021 Category: Cancer & Oncology Source Type: research

Foretinib induces G2/M cell cycle arrest, apoptosis, and invasion in human glioblastoma cells through c-MET inhibition
ConclusionThe results indicated that foretinib might have the therapeutic potential against human GBM which deserve further investigation. (Source: Cancer Chemotherapy and Pharmacology)
Source: Cancer Chemotherapy and Pharmacology - March 10, 2021 Category: Cancer & Oncology Source Type: research