pirarubicin and Pancreatic-Neoplasms

Eighteen patients with either metastatic or locally advanced pancreatic carcinoma were treated with intravenous infusion of Pirarubicin 50 mg/m2/day every 3 weeks. Seventeen patients were evaluable for response. One had minor response, 5 had stable disease, and 11 had progression of disease. Hematological toxicity was moderate, leading to a dose reduction in only 1 patient; there was no clinical cardiac toxicity. We conclude that Pirarubicin used with this dosage and schedule has no activity in advanced pancreatic carcinoma.

Topics: Adult; Aged; Antibiotics, Antineoplastic; Doxorubicin; Drug Administration Schedule; Female; Follow-Up Studies; Humans; Male; Middle Aged; Pancreatic Neoplasms

We developed anticancer drug-conjugated biodegradable polymer-nanoparticle-loaded adipose-derived stem cells (AdSCs) as a tool for biodrug delivery systems for cancer therapy. Pirarubicin was conjugated in polylactic/glycolic acid (PLGA) followed by formation of nanoparticles (NPs), which were loaded with human AdSCs and cocultured. The pirarubicin-conjugated PLGA NP-loaded AdSCs (PirNP-AdSCs) were overall viable within 48 h and exhibited significantly enhanced migration activity. We confirmed that pirarubicin was gradually released into the culture medium from PirNP-AdSCs, and the conditioned medium significantly inhibited the proliferation activity and induced the apoptosis of human pancreatic cancer cells (KP1N). PirNP-AdSCs also significantly induced tumor cell apoptosis in an ex vivo culture system with KP1N-derived tumors, and there was increased invasion/migration of PirNP-AdSCs inside the tumor. Finally, we compared the therapeutic efficacy of the PirNP-AdSCs on KP1N-derived tumor growth with that of treatments of AdSCs alone, PirNPs alone or normal saline (control) in immunodeficient mice. Subcutaneous local administration of PirNP-AdSCs significantly inhibited tumor growth, inducing the apoptosis of tumor cells and vasculature compared with the other groups. The present therapeutic strategy might give rise to a novel cancer therapy minimizing the adverse side effects of anticancer drugs in patients who suffer from cancer.

Topics: Animals; Antineoplastic Agents; Cell Line, Tumor; Cells, Cultured; Culture Media, Conditioned; Doxorubicin; Drug Delivery Systems; Humans; Mesenchymal Stem Cell Transplantation; Mesenchymal Stem Cells; Mice, Inbred NOD; Mice, SCID; Nanoparticles; Pancreatic Neoplasms

Advanced pancreatic cancer is mainly treated by chemotherapy with poor prognosis. This study was designed to evaluate clinical efficacy and application of selective continuous transarterial infusion chemotherapy in treating patients with advanced pancreatic cancer.. Twenty patients with advanced pancreatic cancer were treated by selective continuous transarterial infusion chemotherapy. The interventional treatment was performed with Seldinger technique,12 patients received percutaneous femoral artery cannulization and catheter retention, 8 received percutaneous left subclavian artery port-catheter system implantation. Chemotheraputic drugs were continuously infused when the catheter was selectively placed in turner feeding artery. Nine patients were treated with pirarubicin (THP)/adriamycin (ADM) plus hydroxycamptothecin (HCPT),and 5-fluorouracil (5-FU)/calcium folinate (CF) regimen,and 11 were treated with gemcitabine (GEM) plus carboplatin (CBP),and 5-FU/CF regimen. Treatment regimens were repeated every 4-6 weeks with each cycle of 4 days. Tumor response rate,clinical benefit response (CBR),and survival time were observed.. Objective response rate was 10% with 1 case of complete remission (CR), and 1 case of partial remission (PR), CBR was 70% (14/20), 6-,and 9-month survival rates were 58.8%,and 39.2%. Median survival time for all patients was 8.8 months. No complication related to cannulization was found.. Selective continuous transarterial infusion chemotherapy is safe,and has good efficacy in treating patients with advanced pancreatic cancer, it may prolong survival time of patients.

Topics: Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Camptothecin; Carboplatin; Deoxycytidine; Doxorubicin; Female; Fluorouracil; Gemcitabine; Humans; Infusion Pumps, Implantable; Infusions, Intra-Arterial; Leucovorin; Liver Neoplasms; Lymphatic Metastasis; Male; Middle Aged; Neoplasm Staging; Pancreatic Neoplasms; Remission Induction; Survival Rate

A patient with liver metastasis of pancreatic cancer received chemotherapy using mitomycin C and degradable starch microspheres. The patient was a 52-year-old woman who had undergone surgery for cancer of the head of the pancreas in October 1996. She had stage III disease and was followed up as an outpatient on oral therapy with a combined uracil and tegafur preparation. In October 2000, abdominal computed tomography (CT) scans detected multiple liver metastases. Three courses of intra-arterial infusion of mitomycin C and microspheres (1000 mg) resulted in regression of her tumor and a decrease of tumor marker levels. After three more courses of this therapy, the patient developed bile duct necrosis and died of disseminated intravascular coagulation. As her metastases were controlled for about 7 months, hepatic arterial infusion of mitomycin C and degradable starch microspheres appears to be useful for treating liver metastasis of pancreatic cancer, but careful attention should be paid to the risk of severe complications such as bile duct necrosis.

Topics: Antineoplastic Combined Chemotherapy Protocols; Bile Duct Diseases; Carcinoma, Hepatocellular; Chemoembolization, Therapeutic; Chemotherapy, Adjuvant; Combined Modality Therapy; Doxorubicin; Fatal Outcome; Female; Humans; Infusions, Intra-Arterial; Liver Neoplasms; Middle Aged; Mitomycin; Necrosis; Neoplasm Staging; Pancreatic Neoplasms; Pancreaticoduodenectomy; Risk Assessment; Starch; Tomography, X-Ray Computed

A case of pancreatoblastoma in a 4-year-old girl is presented. She was admitted with an abdominal mass and vomiting in August 1994. Computed tomography scan showed a 10- x 8- x 7-cm mass occupying both the head and body of the pancreas. Serum alpha-fetoprotein (AFP) level was 9,600 ng/mL (normal, <8.3 ng/mL). Results of open biopsy of the tumor showed pancreatoblastoma. Chemotherapy was administered using the new A-1 regimen consisting of cyclophosphamide, etoposide, pirarubicin, and cisplatin. After 3 cycles of chemotherapy, the size of the tumor was reduced to 5 x 4 x 3 cm, the portal vein became patent, and the AFP value decreased to 98.1 ng/mL. Total removal of the tumor was performed leaving the head and tail of the pancreas. Postoperative chemotherapy continued for 2 years. The patient has been disease free for 5 years, and her serum AFP remained within normal levels.

Topics: Antineoplastic Combined Chemotherapy Protocols; Biopsy, Needle; Child, Preschool; Cisplatin; Combined Modality Therapy; Cyclophosphamide; Doxorubicin; Etoposide; Female; Follow-Up Studies; Humans; Neoplasms, Germ Cell and Embryonal; Pancreatectomy; Pancreatic Neoplasms; Time Factors; Tomography, X-Ray Computed; Treatment Outcome

THP-ADM is a new antitumor agent which belongs to the anthracycline family. This agent has shown a high therapeutic index compared with the mother compound, Adriamycin, in preclinical and clinical studies. This time, a pharmacokinetic study of THP-ADM was performed and the following characteristics of this agent were clarified. A short t 1/2 alpha was noted in comparison with that of Adriamycin in a 3-compartment open model. Leukocyte concentration with THP-ADM was much higher than that of plasma of red blood cells. Renal excretion over 48 hours was 9% and biliary excretion over the same period was 20%. High THP-ADM and low Adriamycin tissue concentrations were revealed in all tissues excluding the liver. In liver tissue, a high concentration of Adriamycin and a low concentration of THP-ADM was observed. A small amount of Adriamycin was noted in the plasma following THP-ADM administration. This was probably related to the small amount of existing Adriamycin in THP-ADM or conversion of THP-ADM to Adriamycin in the liver tissue, or both. Poor penetration of THP-ADM into the third space was noted.

Topics: Doxorubicin; Erythrocytes; Humans; Infusions, Intravenous; Kinetics; Lymph Nodes; Pancreatic Neoplasms; Pleural Effusion; Stomach Neoplasms

We tested the effect of Bisantrene (BS) and Theprubicin (THP-ADR) on cell growth of a human pancreatic carcinoma cell line (MIA PaCa-2). After 1 h exposure ID50 of BS or THP-ADR was 3 X 10(-7) and 5 X 10(-8) M, respectively. Increasing the exposure time from 1 h to continuous exposure for 5d resulted in 11-fold decrease in ID50 for BS and a 6-fold decrease for THP-ADR. Both drugs inhibited [14C]thymidine incorporation to the same extent and caused an accumulation of cells into G2 + M phase of the cell cycle.

Topics: Anthracenes; Antibiotics, Antineoplastic; Cell Division; Cell Line; DNA; Doxorubicin; Humans; Pancreatic Neoplasms