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Specific Therapy for Leukemias
Published in Tariq I Mughal, John M Goldman, Sabena T Mughal, Understanding Leukemias, Lymphomas, and Myelomas, 2017
Tariq I Mughal, John M Goldman, Sabena T Mughal
Drugs such as idarubicin and epirubicin are the second generation of anthracyclines. These agents appear less harmful to the heart and idarubicin also appears to be more potent in killing leukemia cells. In 2009, a third generation anthracycline, a synthetic daunorubicin analog called amrubicin, entered the clinics after studies in patients with small cell lung cancer suggested good efficacy and fewer cardiac side-effects. Another related drug, mitozantrone, may also have fewer side-effects than daunorubicin. It belongs to another family (anthraquinones) but resembles anthracyclines in chemical structure and function. It has proven quite useful in the treatment of leukemias and may also have a role in lymphomas. All of these drugs can also produce substantial hair loss which may begin a week after the first injection. The amount of hair lost varies from individual to individual and is usually restricted to the scalp, although pubic, armpit, and facial hair may also be affected. In almost all cases, the hair grows back completely and this is discussed in chapter 11.
Therapeutic options in thymomas and thymic carcinomas
Published in Expert Review of Anticancer Therapy, 2022
Several prospective trials with chemotherapy regimens without anthracyclines have also been conducted. The European Organization for Research and Treatment of Cancer Lung Cancer Cooperative Group (EORTC) study [38], in which cisplatin and etoposide were reported in 16 patients with recurrent or metastatic malignant thymoma, demonstrated an ORR, median PFS, and median OS of 56%, 2.2 years, and 4.3 years, respectively. The combination of cisplatin, etoposide, and ifosfamide was also investigated [39]. Among the 28 patients with advanced thymoma (N = 20) or thymic carcinoma (N = 8), the ORR was 32%, and the median OS was 31.6 months. Another Phase 2 study examined the efficacy of carboplatin plus paclitaxel in 44 patients with thymoma or thymic carcinoma [40]. Among the 21 patients with unresectable thymoma, the ORR was 42.9%, and the median PFS was 16.7 months. In 2014, a Phase 2 study conducted by the North Japan Lung Cancer Group (NJLCG) evaluated the efficacy of a combination of amrubicin and carboplatin [41]. Fifty-one patients with thymic carcinoma or thymoma (including 18 patients with thymoma) were enrolled; the ORR and PFS in the thymoma group were 17% and 7.6 months, respectively. Although the data listed above are from Phase 2 trials or retrospective studies including only few participants, chemotherapy regimens including cisplatin and anthracycline have yielded relatively good results. According to the NCCN guidelines, PAC therapy every 3 weeks is the most recommended treatment [21].
Emerging drugs for small cell lung cancer: a focused review on immune checkpoint inhibitors
Published in Expert Opinion on Emerging Drugs, 2020
Haritha G. Reddy, Angel Qin, Gregory P. Kalemkerian
Lurbinectedin recently received accelerated approval from the FDA based on a single-arm phase II trial that enrolled 105 patients with progression of disease after receiving one prior treatment regimen [26]. Response rate was 35% in all patients, 22% in patients with resistant disease and 45% in those with sensitive disease. In all patients, median PFS and OS were 3.5 months and 9.3 months, respectively, and both survival endpoints were substantially better in patients with sensitive disease. Phase III trials comparing lurbinectedin to standard therapy are on-going. In Japan, amrubicin is available as second-line treatment for SCLC. However, a phase III trial comparing amrubicin vs. topotecan did not demonstrate a survival benefit [27]. In the U.S., two PD-1-targeted ICIs, nivolumab and pembrolizumab, have been FDA-approved for third-line therapy in SCLC based on phase Ib/II clinical trials [28,29].
Current and future therapeutic approaches for the treatment of small cell lung cancer
Published in Expert Review of Anticancer Therapy, 2018
Antonio Rossi, Rebecca Tay, Jaseela Chiramel, Arsela Prelaj, Raffaele Califano
Amrubicin, a fully synthetic 9-aminoanthracycline, has been extensively investigated in Japan in second-line setting. Two randomized phase II trials compared amrubicin, at the dose of 40 mg/m2 on days 1–3, every 3 weeks, to topotecan [57,58] in patients with relapsed disease. In the first study, amrubicin reported a higher ORR (38% vs. 13%) and median PFS (3.5 vs. 2.3 months) without difference in median OS (8.1 vs. 8.4 months) [57]. The second study confirmed these results with an ORR of 44% vs. 15%, for amrubicin and topotecan, respectively (p = 0.02) [58]. These improvements were independently on first-line outcomes and they were reported in Japanese population. A phase III trial enrolling 637 Caucasian patients confirmed a higher ORR (31.1% vs. 16.9%, p < 0.001) for amrubicin compared to topotecan with a median PFS of 4.1 vs. 3.5 months (HR 0.8, p = 0.01), and a median OS of 7.5 vs. 7.8 months (HR 0.88, p = 0.17), respectively. Notably, amrubicin did not improve OS in the whole population, despite median OS reported in the refractory patients was 6.2 vs. 5.7 months (HR 0.77, p = 0.047) [59]. A meta-analysis pooled 803 patients from randomized trials comparing amrubicin versus topotecan in second-line setting. Amrubicin showed a higher ORR and similar OS for sensitive disease while a better OS for resistant relapsed disease was reported with Japanese patients. The toxicity profile was similar except for higher rate of febrile neutropenia [60].