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Applications of Antiviral Nanoparticles in Cancer Therapy
Published in Devarajan Thangadurai, Saher Islam, Charles Oluwaseun Adetunji, Viral and Antiviral Nanomaterials, 2022
Anusha Konatala, Sai Brahma Penugonda, Fain Parackel, Sudhakar Pola
The first priority to treat HCC is to surgically resect the cancer for patients who are suitable candidates. For patients who cannot undergo respective surgery, performing a transplant might be the best option to perform curative therapy. The United Network of Organ Sharing (UNOS) has set out some specific criteria that are used to evaluate transplant eligibility for nonmetastatic (localised) yet unresectable tumours. Ablation, radiation, and embolization are prescribed to patients that do not meet the UNOS criteria as the next priority. Finally, for patients who are not suitable for any of the above treatment strategies and have an unresectable tumour, a management-type approach is taken through systemic treatment. Some of the common systemic treatment options include sorafenib (Colagrande et al. 2016), lenvatinib, bevacizumab (in combination with atezolizumab). Some other commonly used chemotherapeutics include regorafenib, nivolumab, pembrolizumab, cabozantinib, and ramucirumab. Some of the chemotherapeutics that have shown marginal activity in small clinical trials include gemcitabine, capecitabine, and doxorubicin.
Small-Molecule Targeted Therapies
Published in David E. Thurston, Ilona Pysz, Chemistry and Pharmacology of Anticancer Drugs, 2021
Commonly reported side effects of regorafenib include GI disturbances (e.g., mucositis, diarrhea, and decreased appetite), blood dyscrasias (e.g., thrombocytopenia, lymphocytopenia, neutropenia, and anemia), asthenia, fatigue, hemorrhage, hyperbilirubinemia, hypertension, palmar-plantar erythrodysesthesia, proteinuria, and skin rash. Treatment is also associated with a high risk of Gilbert’s syndrome and hyperbilirubinemia. While receiving treatment, patients should be monitored for symptoms of myocardial ischemia, and treatment discontinued if signs develop.
Gastrointestinal Stromal Tumors: From Molecular Pathogenesis to Therapy
Published in Sherry X. Yang, Janet E. Dancey, Handbook of Therapeutic Biomarkers in Cancer, 2021
Joaquina Baranda, Stafinur Atay, Andrew K. Godwin
Regorafenib (Stivarga®) is an oral multi-kinase inhibitor developed by Bayer HealthCare Pharmaceuticals, which targets angiogenic, stromal and oncogenic receptors tyrosine kinase (RTK), including KIT, PDGFR, and VEGFR. It is similar in structure to sorafenib. Regorafenib has a broad-spectrum of anticancer activity. To determine efficacy and safety of regorafenib in patients with metastatic and/or unresectable GI stromal tumor after failure of imatinib and sunitinib, a multicenter single-stage phase II trial was performed and reported by George et al. [132]. Patients received regorafenib orally, 160 mg daily, on days 1 to 21 of a 28-day cycle. Disease assessment was performed every two cycles per RECIST 1.1. Primary end point was clinical benefit rate (CBR), defined as objective responses (i.e., complete or partial response [PR] as well as stable disease [SD] >16 weeks). Thirty-four patients were enrolled at four US centers. CBR was 79% (95% CI, 61% to 91%). Four patients achieved PR, and 22 exhibited SD>16 weeks. Median progression-free survival was 10.0 months. The most common grade 3 toxicities were hypertension and hand-foot-skin reaction. Report of a long-term follow-up of these patients suggests particular benefit among patients with primary KIT exon 11 mutations and those with SDH-deficient GIST [133].
Emerging drugs for the treatment of hepatocellular carcinoma
Published in Expert Opinion on Emerging Drugs, 2022
Walid S Ayoub, Patricia D. Jones, Ju Dong Yang, Paul Martin
Regorafenib, a multikinase inhibitor, was the first agent to be approved as a second-line therapy for HCC in 2017. The RESORCE trial included 567 patients with Child A cirrhosis and advanced HCC progression on previous treatment with sorafenib. It was the first positive phase 3 trial in second-line advanced HCC. Patients were randomized to receiving regorafenib vs. placebo. Regorafenib was associated with an OS of 10.6 months vs 7.8 months in the placebo group (p < 0.0001) and an HR of 0.63 (95% CI 0.5–0.79). The ORR was 11% (CR 2 patients, PR 38) in the regorafenib group compared to 4% in the placebo group (CR 0, PR 8). PFS was better in the regorafenib group compared to placebo (3.1 months vs 1.5 months)[32]. Regorafenib is approved for the treatment of colorectal cancer, gastrointestinal stromal tumor (GIST), and HCC.
Prolonged clinical response with regorafenib administered as second-line therapy in an elderly patient suffering from peritoneal carcinomatosis of colon cancer
Published in Journal of Chemotherapy, 2021
In January 2017, full dose regorafenib (160 mg/day for 21 days, every 4 weeks) was initiated as a second-line treatment for metastatic disease. Basal and serial serum levels of carcinoembryonic antigen (CEA) and CA 19-9 are shown in Table 1. The patient was monitored weekly for the first 2 cycles due not only for the possible appearance of resistant hypertension, but above all for liver and skin toxicity. The typical toxicities of regorafenib were however absent. On the contrary, thrombocytopenia and neutropenia grade 1-2 were reported with the postponement of cycles, each time of 7-10 days. In April, a PET/CT (Figure 1C and D) showed a partial remission (PR) of disease. Starting from the 3rd cycle, the regorafenib dose was reduced to 120 mg/day. The patient then continued treatment at the same dose maintaining PR (Figure 2) for a total of 23 cycles, at the price of a modest hoarseness and above mentioned haematological toxicity. In July 2019, after 30 months from the start of regorafenib, the patient showed a progression of disease with the detection of new peritoneal carcinomatosis nodules (Figure 3).
Regorafenib, an investigational agent for the treatment of cholangiocarcinoma
Published in Expert Opinion on Investigational Drugs, 2021
Ibrahim Halil Sahin, Elaine Tan, Richard Kim
Regorafenib has been investigated in early clinical studies to evaluate the safety profile of this agent and early clinical signs of clinical efficacy. In a dose–escalation study of regorafenib, the author investigated the regorafenib in 53 advanced stage solid tumor patients [30]. The patients have received dose levels between 10 to 220 mg daily and 160 mg once-daily oral dose was determined to be the maximum-tolerated dose and was recommended phase II dose. The authors also investigated the pharmacodynamics of the regorafenib monotherapy and reported a reduction of plasma VEGFR2 concentration over the various time points during the cycles of treatment. Early efficacy outcomes of regorafenib were also assessed in this study. The authors reported 3 (6%) of ORR and 60% of patients had stable disease as the best response. The patients who achieved partial response in this study had colorectal cancer, renal cell carcinoma, and osteosarcoma. The authors also reported durable disease control in a pancreatic adenocarcinoma patient with ongoing 21 months of stable disease.