Disease relevance of Therarubicin

• Phase II clinical and pharmacological study of pirarubicin in combination with 5-fluorouracil and cyclophosphamide in metastatic breast cancer [1].
• A significant decrease in left ventricular ejection fraction occurred in 12 patients (at a median cumulative pirarubicin dose of 460 mg/m2) and led to congestive heart failure in 4 of these patients (cumulative pirarubicin doses of 500, 520, 590, and 730 mg/m2, respectively) [1].
• Studies from our laboratory have also shown that TRAIL-resistant renal cell carcinoma, prostate gland cancer, and bladder cancer cells are sensitized by subtoxic concentrations of chemotherapeutic drugs including doxorubicin, epirubicin, pirarubicin, and cisplatin [2].
• Biweekly THP-COPBLM including pirarubicin (THP), which is thought to be less toxic than doxorubicin, was used to treat non-Hodgkin's lymphoma (NHL) and the remission rate and adverse events were studied in 42 patients younger than 69 years [3].
• Pharmacology and antitumour effects of intraportal pirarubicin on experimental liver metastases [4].

High impact information on Therarubicin

• Two anthracyclines, the doxorubicin derivative pirarubicin and 2'-bromo-4'-epi-DNR seemed to have a slightly higher Ka value for Pgp than for MRP [5].
• Eleven patients underwent endomyocardial biopsy, either because they experienced a drop in left ventricular ejection fraction or because they had received a cumulative pirarubicin dose of 600 mg/m2 and were still responding to the treatment [1].
• Evidence for reversal of multidrug resistance by quinine in LR73 cells without alteration of nuclear pirarubicin uptake and down-regulation of mdr1 gene expression [6].
• PURPOSE: To evaluate the safety and efficacy of a modified version of cyclophosphamide, doxorubicin, vincristine, prednisone (pirarubicin, cyclophosphamide, vincristine, and prednisone [THP-COP]) plus radiotherapy for early-stage aggressive non-Hodgkin's lymphoma of the head and neck [7].
• First-line hepatic infusion of pirarubicin in patients with isolated liver metastases: is it really promising [8]?

Chemical compound and disease context of Therarubicin

• We conducted a Phase II trial of an anthracycline analogue, pirarubicin, administered in combination with 5-fluorouracil and cyclophosphamide every 3 weeks, as front-line chemotherapy in women with metastatic breast cancer [1].
• Data of all phase II studies of pirarubicin (THP-doxorubicin) have been analysed for toxicity or activity in breast cancer and compared with published reports on doxorubicin, epirubicin or mitoxantrone used as single drugs [9].
• Combination chemotherapy with pirarubicin (THP), cyclophosphamide, vincristine, and prednisolone (VEP-THP therapy) in the treatment of non-Hodgkin's lymphoma [10].
• Furthermore, in mice with hepatic neoplastic nodules of colon adenocarcinoma 26, ME2303 also showed a marked antitumour effect compared to pirarubicin or doxorubicin [11].
• Five anthracycline derivatives, i.e. doxorubicin, epirubicin, pirarubicin, aclarubicin and a new fluorinated anthracycline derivative (ME2303), were tested for antitumour activity in mice with hepatic neoplastic nodules of Lewis lung carcinoma and colon adenocarcinoma 26 [11].

Biological context of Therarubicin

• Pirarubicin also induced apoptosis, however, its apoptosis was significantly (p = 0.0069) less than that induced by ADR [12].
• When drug-sensitive cells were incubated with pirarubicin, the spectrum recorded from inside the nucleus was characteristic of anthracycline intercalated between the base pairs in the nucleus [13].
• Pharmacokinetics and metabolism of pirarubicin in humans: correlation with pharmacodynamics [14].
• A relationship was observed between some pharmacokinetic parameters and the toxic effects of the drug: the percentage of survival of granulocytes was significantly correlated with the AUC values for doxorubicin and doxorubicinol, whereas that of platelets was significantly correlated with the AUC values for pirarubicin and pirarubicinol [15].
• As the intranuclear concentration of pirarubicin is dependent on nuclear transport, the increases in not only cell membrane transport, but also nuclear membrane transport contributed to the enhancement of the efficacy of pirarubicin [16].

Anatomical context of Therarubicin

• Effect of granulocyte colony-stimulating factor administration in elderly patients with aggressive non-Hodgkin's lymphoma treated with a pirarubicin-combination chemotherapy regimen. Groupe d'Etudes des Lymphomes de l'Adulte [17].
• Pirarubicin may therefore be considered to be an anthracycline without marked side-effects on gastric mucosa [18].
• These compounds have the same efficacy as verapamil to increase pirarubicin (pira) incorporation into living multidrug resistant (MDR) K562 cells and to sensitize them to the cytotoxic effect of this anthracycline derivative, indicating that they act as typical MDR modifiers in MDR cells [19].
• Comparative evaluation of pirarubicin and adriamycin in gynecologic cancer cell lines [20].
• Possibility of contribution of nucleoside transport systems to pirarubicin uptake by HL60 cells but not mononuclear cells [21].

Associations of Therarubicin with other chemical compounds

• The ADR analogs, epirubicin and pirarubicin, also enhanced the susceptibility of bladder cancer cells to lysis by autologous PBL [22].
• The copolymer of styrene-maleic acid (SMA) was used to construct micelles containing pirarubicin (4'-O-tetrahydropyranyladriamycin, or THP) as a new anticancer drug formulation [23].
• CONCLUSION: Embosphere microspheres can be mixed with carboplatin, mitomycin C, 5-fluorouracil, or pirarubicin for chemoembolization therapy without any risk of damaging their morphology, dimensions, or geometric characteristics [24].
• The patient received THP-COP chemotherapy (pirarubicin, cyclophosphamide, vincristine, and prednisolone) and radiotherapy, achieved complete remission, and was free of disease for 16 months after treatment [25].
• We performed chemotherapy with two courses of 5-fluorouracil, pirarubicin hydrochloride, and mitomycin-C, resulting in no beneficial effect [26].

Gene context of Therarubicin

• The activity of latent benzoperimidine esters to inhibit P-glycoprotein and multidrug resistance-associated protein 1 dependent efflux of pirarubicin from several lines of multidrug resistant tumor cells [27].
• Fas antigen was overexpressed in the hearts of ADR and ADR+FasL groups, however, an expression of Fas antigen in the pirarubicin group was similar to the expression of Fas antigen in the control group [12].
• Artemisinin, artesunate and dihydroartemisinin increased cytotoxicity of pirarubicin and doxorubicin in P-glycoprotein-overexpressing K562/adr, and in MRP1-overexpressing GLC4/adr, with the delta(0.5) ranging from 200 to 860 nM, but not in their corresponding drug-sensitive cell lines [28].
• In the present study we examined the effects of pirarubicin [(2"R)-4'-O-tetrahydropyranyladriamycin, THP] on a cardiovascular system [29].
• In vivo, pirarubicin cured DHD/K12/PROb-inoculated rats, even at the site of the peritoneal scarring and intestinal anastomosis. i.p. pirarubicin prevented the development of peritoneal carcinomatosis and liver metastasis in LS174T-inoculated mice. i.p. washing with pirarubicin cured 2-day-old, but not 7-day-old, peritoneal carcinomatosis in rats [30].

Analytical, diagnostic and therapeutic context of Therarubicin

• Twenty one patients with either metastatic or inoperable locally advanced bladder carcinoma were treated with intravenous infusion of pirarubicin: 25 mg/m2/day for 3 days every 4 weeks in the first 15 patients and 20 mg/m2/day for 3 days every 3 weeks in the others [31].
• Mice survived for more than 1 year after treatment with micellar drug doses as high as 100 mg/kg pirarubicin equivalent [23].
• Antitumoral efficacy and pharmacokinetic properties of pirarubicin upon hepatic intra-arterial injection in the rabbit V x 2 tumour model [32].
• Twenty one patients with hormone resistant prostate cancer were entered in a phase II study of pirarubicin 70 mg/m2, as a single intravenous injection given at 21 day intervals [33].
• In M5076 solid tumor-bearing mice, pirarubicin reduced the tumor weight to 60% of the control level, although doxorubicin had no effect [16].

References