Salvage chemotherapy with methotrexate, etoposide and actinomycin D in men with metastatic nonseminomatous germ cell tumors with a choriocarcinoma component: A preliminary report

Abstract

Abstract:The objective of the present study was to assess the use of salvage chemotherapy using methotrexate, etoposide and actinomycin D (MEA) in men with nonseminomatous germ cell tumor (NSGCT) with a choriocarcinoma component. Nine patients were included. They had initially received bleomycin, etoposide and cisplatin, and high-dose ifosfamide, carboplatin and etoposide as induction chemotherapies. However, they failed to achieve the normalization of b-human chorionic gonadotropin (b-HCG). Therefore, MEA therapy (methotrexate: 450 mg/body on day 1, actinomycin D: 0.5 mg/body on days 1-5, etoposide: 100 mg/body on days 1-5) was subsequently administered. After MEA therapy (median: 3 cycles), serum b-HCG was normalized in five of the nine patients. Of these five, three achieved long-term disease-free survival and one died of disease unrelated to NSGCT, whereas the remaining patient developed disease recurrence and died of disease progression. All four patients who failed to achieve the normalization of b-HCG died of disease progression. Although several severe toxicities greater than grade 3, which were mainly associated with bone marrow suppression, occurred in all patients, there was no treatment-related death. Considering the current outcomes, MEA regimen could be an attractive option as a salvage chemotherapy for metastatic NSGCT patients with a choriocarcinoma component showing resistance to intensive conventional chemotherapies.

Low‐Dose Actinomycin‐D Induces Redistribution of Wild‐Type and Mutated Nucleophosmin Followed by Cell Death in Leukemic Cells

“…Actinomycin D (Dactinomycin, actD), an antitumor antibiotic inhibiting transcription, is one of the oldest chemotherapy drug used to treat various cancer types [Ward, ; Terakawa et al, ]. Pharmacokinetic studies of actD reported a median plasma concentration about 100 ng/ml (i.e., 80 nM) [Hill et al, ].…”

An overview of recent advances in duplex DNA recognition by small molecules

“…Several DNA intercalating drugs have been identified over the years, which include daunomycin (trade name Cerubidine), doxorubicin (trade name Adriamycin), epirubicin (anthracycline family), dactinomycin (trade name Cosmegen), ditercalinium, bleomycin, elsamicin A, m-AMSA, mitoxantrone, acridines, ethidium bromide and so on ( Fig. 14 ) [ 30 , 148 – 151 ]. Anthracyclines are a class of antitumor antibiotics, isolated from Streptomyces species, mostly used in various cancer chemotherapy such as acute leukemia, Hodgkin’s and non-Hodgkin’s lymphoma, breast and ovarian cancer, lung cancer, gastric (stomach) cancer, testicular cancer, bladder cancer and soft tissue sarcoma etc.…”

Treatment of patients with relapsed and/or cisplatin‐refractory metastatic germ cell tumours: an update

“…, 2010a,b). A Japanese group of investigators very recently demonstrated that the use of a combination regimen of methotrexate, etoposide and actinomycin D could be an option after failure to HDCT as a salvage chemotherapy for patients with a choriocarcinoma component in their tumours (Terakawa et al. , 2010).…”

“…In a group of 76 heavily pre-treated relapsed patients, including patients previously treated with HDCT (78%) or showing cisplatin-refractory disease (73%), a PFS of 17 and 3% was seen after a 2 year follow-up among the patients treated with the combination of gemcitabine, oxaliplatin and paclitaxel (GOP), or gemcitabine and oxaliplatin, respectively (Oechsle et al, 2010a,b). A Japanese group of investigators very recently demonstrated that the use of a combination regimen of methotrexate, etoposide and actinomycin D could be an option after failure to HDCT as a salvage chemotherapy for patients with a choriocarcinoma component in their tumours (Terakawa et al, 2010).…”