pirarubicin and Carcinoma

Eighty patients with measurable metastatic colon or renal cancer, melanoma, or sarcoma entered these Phase II studies. A dose of 25 mg/m2/day of Pirarubicin (THP) for 3 consecutive days every 4 weeks for the first patients, and then 20 mg/m2/day for 3 days every 3 weeks was given by i.v. push. These patients received 225 cycles for a median cumulative dose of 165 mg/m2 (range: 55-630). The mean number of cycles given was 2.8 (range: 1-8). Only 3 partial responses and 18 stable disease (22%) were observed. Hematologic toxicity was the main problem; it was responsible for one death and a 19% and 44% incidence of grade 3 and 4 WHO neutropenia, respectively. Alopecia was rare (4%). Chemotherapy was discontinued in three cases because of suspicion of cardiac toxicity, but only one patient had a significant drop in left ventricular ejection fraction at a cumulative THP dosage of 120 mg/m2. A lack of efficacy in renal and colon cancer and melanoma was presupposed and confirmed by these trials. Due to pretreatment with anthracycline in most patients, definite evaluation of THP in soft tissue sarcoma could not be given.

Topics: Adult; Aged; Antibiotics, Antineoplastic; Carcinoma; Colonic Neoplasms; Doxorubicin; Drug Administration Schedule; Humans; Kidney Neoplasms; Melanoma; Middle Aged; Sarcoma; Soft Tissue Neoplasms

To assess the changes in estrogen receptor (ER), progesterone receptor (PR), human epidermal growth factor receptor 2 (HER2) and Ki-67 expression in breast cancer patients after various neoadjuvant chemotherapies. Data from 138 locally advanced breast cancer patients with histological diagnoses were reviewed. Seventy patients (group 1) were given 4 cycles of 500 mg/m(2) cyclophosphamide and 50 mg/m(2) pirarubicin every 21 days. Sixty-eight patients (group 2) were given 4 cycles of 500 mg/m(2) cyclophosphamide and 75 mg/m(2) docetaxel every 21 days. The biomarker changes of the operated tumor tissues were compared with the initial core biopsies. ER, PR, HER2 and Ki-67 expression changed by 28.6%, 22.9%, 17.1% and 54.3%, respectively, after neoadjuvant chemotherapy in group 1 and 16.2%, 22.1%, 13.2% and 70.6%, respectively, after neoadjuvant chemotherapy in group 2. There were significant differences between the groups regarding ER and Ki-67 status changes, and these changes can be used to inform treatment strategies.

Topics: Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Biomarkers, Tumor; Breast Neoplasms; Carcinoma; Cyclophosphamide; Docetaxel; Doxorubicin; Female; Humans; Ki-67 Antigen; Middle Aged; Neoadjuvant Therapy; Receptor, ErbB-2; Receptors, Estrogen; Receptors, Progesterone; Taxoids

We evaluated antitumoral effect of combined chemotherapy and interleukin-12 (IL-12) gene therapy in in vitro and in vivo experimental urothelial bladder cancer (UBC) model.. EJ UBC cells were transfected with recombinant IL-12 genes using a liposomal transfection agent. Pirarubicin (THP) was added to the experimental samples at a final concentration of 20 mg/l. Four groups were assigned in vitro: untreated cells, transfected cells, untransfected cells plus THP and transfected cells plus THP. Death rates (DR) and cellular micromorphologic changes were evaluated. Bladder tumor model was established by subcutaneous injection of EJ cells to the nude mice. Four groups were assigned in vivo: control group; THP group; IL-12 gene group and IL-12 gene plus THP group. After injection of combined THP and IL-12 gene therapy, tumor size and IL-12 levels were evaluated.. In vitro study: DR in the THP + IL-12 gene therapy group (58.2 ± 15.8%) was significantly higher than transfected group (12.2 ± 5.6%; P = 0.01) and untransfected cells plus THP group (33.4 ± 7.8; P = 0.046). A higher amount of apoptotic changes and necrosis on transmission electron microscope analysis were observed in transfected cells plus THP group. In vivo study: A significant tumor attenuation was found in IL-12 gene in combination with THP group when compared with any other groups that were treated without Il-12 or THP (P < 0.05). IL-12 levels in serum were significant high in IL-12 gene groups (P < 0.01).. The combination of THP chemotherapy and IL-12 gene therapy showed an additive antitumoral effect on bladder cancer cells in vitro and in vivo. Further investigation should be focused on high-level transgene protocols in vivo.

Topics: Animals; Antineoplastic Agents; Apoptosis; Carcinoma; Cell Line, Tumor; Combined Modality Therapy; Doxorubicin; Genetic Therapy; Humans; Interleukin-12; Mice; Mice, Inbred BALB C; Mice, Nude; Models, Animal; Transfection; Tumor Burden; Urinary Bladder Neoplasms

This concurrent chemoradiotherapy with CPA, THP, and CDDP showed major antitumor activity with manageable toxicity as treatment of advanced salivary gland carcinoma patients. The high response rate (RR) justifies further evaluation of this chemoradiotherapy combination.. The aim of this study was to evaluate the efficacy and toxicity of a concurrent chemoradiotherapy using cyclophosphamide (CPA), pirarubicin (THP), and cisplatin (CDDP) in patients with locally advanced salivary gland carcinoma.. Seventeen patients with previously untreated stage III-IV salivary gland carcinoma were entered in this trial between January 2000 and September 2005. Chemotherapy consisted of CPA 400 mg/m2 on day 1, THP 40 mg/m2 by 6-h infusion on day 1, and CDDP 60 mg/m2 by 2-h infusion on day 1. Radiotherapy (2.0 Gy/fraction/day, mean total dose: 67.2 Gy (64.0-72.0 Gy)) administered 5 days per week, was targeted to begin on day 1.. The RR was 76% (13/17) and the pathological complete response (CR) was 24% (4/17). The primary site CR was 29% (5/17) and metastatic lymph node CR was 33% (4/12). The 5-year survival rate was 70%. Neutropenia, leukocytopenia and mucositis were common adverse effects, but all 17 patients were assessable for toxicity.

Topics: Aged; Antineoplastic Combined Chemotherapy Protocols; Carcinoma; Cisplatin; Combined Modality Therapy; Cyclophosphamide; Doxorubicin; Female; Humans; Male; Middle Aged; Salivary Gland Neoplasms

Free malignant cells, which are frequently detected in the washing liquid from the peritoneal cavity before and after resection of human colorectal cancer, are suspected to cause recurrent peritoneal cancer. We carried out an experimental study to compare the prophylactic efficacy of washing the peritoneum with several anticancer drugs and the antiseptic povidone-iodine against the development of peritoneal carcinomatosis from colonic origin in rats and nude mice. The in vitro anticancer activity of a short, 15-minute exposure of pirarubicin, doxorubicin, 5-fluorouracil, cisplatin, mitomycin C, and 1% povidone-iodine was first evaluated by an MTT assay on DHD/K12/PROb rat and LS174T human colon cancer cells. For the in vivo experiments, BDIX rats were inoculated intraperitoneally (i.p.) with 1 x 10(6) DHD/K12/PROb cells followed by peritoneal scarring and a colocolic anastomosis. A 15-minute peritoneal washing with the anticancer drugs or povidone-iodine was then performed. Nude mice were i.p.-inoculated with 1 x 10(7) LS174T human cells and treated 2 hours later with i.p. pirarubicin. Only pirarubicin, mitomycin C, and povidone-iodine were fully cytotoxic in vitro against DHD/K12/PROb rat colon cancer cells. In contrast to pirarubicin and povidone-iodine, mitomycin C was not completely active against LS174Tcells. 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. Short exposure to i.p. pirarubicin is nontoxic and more active than povidone-iodine and other anticancer drugs in preventing the development of peritoneal carcinomatosis from colonic origin in rats and mice. The prophylactic effect of preoperative peritoneal washing with pirarubicin on the development of recurrent peritoneal cancer should be evaluated in a randomized clinical trial.

Topics: Animals; Anti-Infective Agents, Local; Antineoplastic Agents; Carcinoma; Cell Line, Tumor; Colonic Neoplasms; Doxorubicin; Immunosuppressive Agents; Injections, Intraperitoneal; Male; Mice; Mice, Nude; Neoplasm Seeding; Peritoneal Lavage; Peritoneal Neoplasms; Pharmaceutical Solutions; Povidone-Iodine; Rats

We report a case of advanced ureteral cancer successfully treated with systemic chemotherapy combined with irradiation. A 47-year-old man was diagnosed as having a right ureteral cancer at the clinical stage of T4, N2 and M1 (liver). A papillary tumor was also found in the bladder and the resected specimen showed a grade 1 transitional cell carcinoma. Although three cycles of methotrexate, vinblastine, pirarubicin and cisplatin (MVAC) gave partial response to the ureteral tumor, new metastases to the lung and pelvic bone were observed. The patient received 50 Gy external irradiation to the pelvis, 11 cycles of paclitaxel (270 mg) and cisplatin (60-80 mg) followed by four cycles of docetaxel (100 mg) and cisplatin. Thereafter, he underwent bone biopsy, partial hepatectomy, total nephroureterectomy and lymph node resection, by which a complete response was achieved pathologically. The patient has been alive without evidence of disease for 12 months.

Topics: Antineoplastic Combined Chemotherapy Protocols; Biopsy, Needle; Carcinoma; Chemotherapy, Adjuvant; Cisplatin; Combined Modality Therapy; Dose-Response Relationship, Drug; Doxorubicin; Drug Administration Schedule; Follow-Up Studies; Humans; Magnetic Resonance Imaging; Male; Methotrexate; Middle Aged; Neoplasm Staging; Paclitaxel; Radiotherapy, Adjuvant; Tomography, X-Ray Computed; Treatment Outcome; Ureteral Neoplasms; Vinblastine

Early liver metastases have a predominant portal blood supply. Intraportal (i.port.) vein administration of cytotoxics could theoretically achieve enhanced drug concentrations in tumour cells and be effective as adjuvant therapy after resection of colorectal carcinoma. Pirarubicin (which has a higher hepatic extraction than doxorubicin) was investigated on liver metastases of the VX2 rabbit tumour, which were of less than 2 mm in diameter 7 days after cells injection into the portal vein. To evaluate antitumour activity, 24 rabbits were randomised into three groups 7 days after implantation: (a) control, (b) i.v. pirarubicin, (c) i.port. pirarubicin at doses of 2 mg kg-1 in both groups. Portal infusions led to no hematological or hepatic toxicity. Pharmacokinetic parameters showed a significantly reduced systemic exposure after i.port. administration. Fourteen days after treatment, livers and lungs were analysed. The mean number (+/- s.d.) of tumour foci was (a) 8.62 (+/- 5.4), (b) 4.62 (+/- 3.2), (c) 2.25 (+/- 1.4) (P < 0.05 a vs c). The mean tumour area was (a) 6.31 (+/- 6.1), (b) 1.31 (+/- 2.2), (c) 0.43 (+/- 0.4 cm2) (P < 0.05 a vs c) and the percentage (95% C.I.) of rabbits with lung metastasis was: (a) 87.5% (47-99%), (b) 75% (35-97%), (c) 12.5% (3-52%) (P < 0.02 b vs c). Intraportal pirarubicin seems to be well tolerated and more efficient than i.v. administration, particularly in preventing extrahepatic dissemination.

Topics: Animals; Antibiotics, Antineoplastic; Carcinoma; Doxorubicin; Infusions, Intravenous; Liver Neoplasms; Portal Vein; Rabbits

One-day CAP therapy utilizing CPM, THP-ADM and CDDP was performed on 33 patients with malignant tumors in the head and neck region which were able to be evaluated. As a result, CR was obtained in 6 patients and PR in 11 patients; thus the overall response rate was 51.5%. The present therapy is worthwhile as a neo-adjuvant chemotherapy and it was effective in patients with relatively severe systemic condition or those with lung metastasis. When the tissues were classified histologically, the present therapy was effective against anaplastic carcinoma and adenocarcinoma. Since agents significantly effective against adenocarcinoma have not been available so far, the present therapy is considered to be a useful method especially for the treatment of adenocarcinoma. Moreover, because irreversible side effects scarcely appeared and because the period for 1 course of treatment is short enough, the present therapy is considered to be a method with little burden on patients.

Topics: Adenocarcinoma; Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Carcinoma; Carcinoma, Squamous Cell; Cisplatin; Cyclophosphamide; Doxorubicin; Female; Head and Neck Neoplasms; Humans; Lung Neoplasms; Lymphatic Metastasis; Male; Middle Aged