peplomycin and pirarubicin

Topics: Aclarubicin; Anti-Bacterial Agents; Antibiotics, Antineoplastic; Bacteria; Benzodiazepinones; Bleomycin; Chemistry; Doxorubicin; Fungi; History, 20th Century; Japan; Maytansine; Naphthacenes; Peplomycin; Peptide Biosynthesis; Peptides; Structure-Activity Relationship

Intra-arterial neoadjuvant chemotherapy (TPP) with pirarubicin, cisplatin and peplomycin produced strong primary effects on oral squamous cell carcinoma, using metoclopramide (MCA) as an anti-emetic. After clinical application of granisetron (GRN), the clinical responses to TPP observed previously were weakened. In this paper, the influence of GRN on TPP is discussed. Sixty-three cases were evaluated with regard to the primary effects of TPP and anti-emetics. GRN was used in 42 cases of the GRN group, and MCA in 21 cases of non-GRN group. The clinical response rate (complete response, CR or partial response, PR) was 95.2% in the non-GRN group, and 76.2% in the GRN group. The rate of CR in the non-GRN group was 47.6%, whereas it was 9.5% in the GRN group. The histological effects in the GRN group were significantly lower (P<0.05) than those of non-GRN group. Concerning the relationship between the clinical responses and the histological responses, 4 of the 18 CR+PR cases (22.2%) in the GRN group showed good histological responses, compared with 6 of the 14 CR+PR cases (42.9%) showing in the non-GRN group. The histological responses in the GRN group were significantly lower (P<0.05) than in the non-GRN group. Our data indicate that GRN reduces the clinical and histological responses of chemotherapy.

Topics: Antiemetics; Antineoplastic Combined Chemotherapy Protocols; Carcinoma, Squamous Cell; Chi-Square Distribution; Cisplatin; Cohort Studies; Doxorubicin; Drug Interactions; Female; Granisetron; Humans; Injections, Intra-Arterial; Male; Middle Aged; Mouth Neoplasms; Peplomycin; Retrospective Studies

We report a case of regionally metastatic pure squamous cell carcinoma of the urinary bladder successfully treated with combined radiation and chemotherapy in a 46-year-old man. Clinical staging was T3bN2M0. The patient received 50 Gy external radiation combined with intraarterial and systemic chemotherapy. Pathological complete response was found both in bladder and regional lymph nodes when he underwent radical cystectomy and lymph node dissection. The patient has been alive without evidence of disease for two years postoperatively.

Topics: Antineoplastic Combined Chemotherapy Protocols; Carcinoma, Squamous Cell; Cisplatin; Combined Modality Therapy; Doxorubicin; Humans; Lymph Nodes; Lymphatic Metastasis; Male; Middle Aged; Peplomycin; Radiotherapy Dosage; Urinary Bladder Neoplasms

The effects of an induction chemotherapy with THP-adriamycin, cisplatin, and peplomycin (TPP) were studied in 32 patients with operable oral cancer. The histological evaluation according to the Shimozato-Oboshi classification was Grade (G) IV in ten cases (31.3%), GIII in one case, and GIIb in four cases. Induction of apoptosis and differentiation-inducing effects, hyperkeratinization or bone formation, were observed in some cases. The overall clinical response rate and histological response rate were 63% and 47%, respectively. Grade III was obtained in seven metastatic lymph nodes of three patients. The expressions of PCNA, p53, and AgNORs before and after chemotherapy were studied. The prechemotherapeutic PCNA positive cell index (PI) of the highly responsive tumors (GIII, IV) was significantly lower than that of the poorly responsive tumors (G0-IIb) (P < 0.01). Similar results were obtained in the evaluation of p53 PI (P < 0.05), suggesting that PCNA and p53 are useful biomarkers for predicting the efficacy of TPP chemotherapy.

Topics: Antibiotics, Antineoplastic; Antineoplastic Agents; Antineoplastic Combined Chemotherapy Protocols; Apoptosis; Biomarkers, Tumor; Carcinoma, Squamous Cell; Cell Differentiation; Cisplatin; Coloring Agents; Doxorubicin; Female; Forecasting; Gene Expression Regulation, Neoplastic; Humans; Keratins; Lymphatic Metastasis; Male; Middle Aged; Mouth Neoplasms; Nucleolus Organizer Region; Osteogenesis; Peplomycin; Proliferating Cell Nuclear Antigen; Remission Induction; Silver; Treatment Outcome; Tumor Suppressor Protein p53

The present paper investigates the pharmacokinetics of pirarubicin (THP) in the plasma and cerebrospinal fluid (CSF) of two patients with glioma during hyperosmotic disruption of the blood-brain barrier (HODBBB) and intra-arterial combination chemotherapy. A 42-year-old Japanese man (patient A) with glioblastoma and a 21-year-old Japanese woman (patient B) with astrocytoma received a course of HODBBB and intra-arterial combination chemotherapy with THP, methotrexate, peplomycin, and vindesine. Patient A was initially administered mannitol, followed by the infusion of anticancer drugs into the right internal carotid artery. Patient B was initially administered mannitol, followed by the infusion of anticancer drugs into the right internal carotid artery and, immediately thereafter, into the right vertebral artery. Samples of blood and of CSF in the brain ventricle were obtained. THP concentration was measured by HPLC, and the pharmacokinetic parameters of this drug were estimated in plasma and CSF. In both patients, the plasma concentration of THP peaked at the end of infusion, then decreased in a bi-exponential decay pattern during the remainder of the treatment period. THP was detectable in CSF beginning 1.0 h after the initiation of infusion, then was slowly eliminated from the ventricle. The maximum CSF concentration of THP was 0.97% of plasma in patient A and 0.89% in patient B. The CSF AUC of THP was 28.4% of plasma in patient A and 13.1% in patient B.

Topics: Adult; Antineoplastic Combined Chemotherapy Protocols; Blood-Brain Barrier; Brain Neoplasms; Doxorubicin; Female; Glioma; Humans; Infusions, Intra-Arterial; Methotrexate; Peplomycin; Vindesine

We investigated the clinical usefulness of individualization of chemotherapeutic regimen in neoadjuvant intra-arterial chemotherapy for locally invasive bladder cancer. Anticancer drugs were selected according to the results of an in vitro chemosensitivity test (collagen matrix assay or succinic dehydrogenase inhibition test). Nine patients with locally invasive bladder cancer received 1 to 4 courses of neoadjuvant intra-arterial chemotherapy, followed by radical cystectomy. Histopathological responses in the cystectomized specimens were grade 3 in 3 cases, grade 2 in 2, grade 1b in 2 and no response in 2. Pathologically, a complete response and downstaging were observed in 3 and 4 cases, respectively. Seven of the 9 patients were alive no evidence of disease with a mean follow-up period of 38.9 months, whereas 2 patients died of metastasis within 2 years. Six of the 7 patients who showed a complete response or down staging have been free of recurrence. These findings suggest that our chemotherapeutic strategy may improve the prognosis for locally invasive bladder cancer.

Topics: Aged; Antineoplastic Combined Chemotherapy Protocols; Chemotherapy, Adjuvant; Cisplatin; Doxorubicin; Drug Administration Schedule; Drug Screening Assays, Antitumor; Epirubicin; Etoposide; Female; Fluorouracil; Humans; Infusions, Intra-Arterial; Male; Middle Aged; Mitomycin; Peplomycin; Prognosis; Tumor Cells, Cultured; Urinary Bladder Neoplasms; Vinblastine

Head and neck cancer has hypoxic compartment. The hypoxic cells are resistant to anticancer drugs and thought to be one of the causes of recurrence. We examined effects of anticancer drugs on the hypoxic cells using HEp-2 human laryngeal cell line. Anticancer drugs, CDDP, peplomycin (PEP), 5-FU, THP-adriamycin (THP-ADR), and adriamycin (ADR), were incubated with cells in hypoxic condition (5% CO2 and 95% N2) for 72 hours. Drug effects were measured by proliferation rates (IC50). IC50 of PEP increased 22.89 folds in hypoxic cells. IC50 of CDDP and 5-FU also increased 1.86 and 2.27 folds respectively. However, IC50 of THP-ADR and ADR remained same in the hypoxic cells. It was proved that THP-ADR and ADR were effective for the hypoxic cells. The combination effect with THP-ADR and CDDP or PEP were more than additive against the hypoxic cells. It was suggested that the combination with THP-ADR and CDDP or PEP are effective for head and neck cancer which contains hypoxic cell compartment.

Topics: Antibiotics, Antineoplastic; Antineoplastic Combined Chemotherapy Protocols; Cell Division; Cell Hypoxia; Cisplatin; Doxorubicin; Drug Synergism; Head and Neck Neoplasms; Humans; Peplomycin

We have examined the therapeutic effects of combination therapy of pirarubicin ((2"R)-4'-O-tetrahydropyranyladriamycin, THP) with various antitumor agents against P388 murine leukemia. THP showed a high antitumor activity in combination with various antitumor drugs, especially with cyclophosphamide (CPM), cisplatin (CDDP), mitomycin C (MMC), enocitabine (BHAC), vindesine (VDS) or methotrexate (MTX). The effects of combination therapy depended on the order of administration of THP and combined drugs. THP-preceding treatment gave more synergistic effects in combination with 5-fluorouracil (5-FU) or MTX. THP-preceding or simultaneous treatment with etoposide (ETP) indicated the higher synergistic activity than ETP-preceding one. Moreover, THP showed much higher synergistic effects in any order of the combination with CPM, CDDP, MMC, BHAC, VDS or MTX. These results suggest that THP possesses a therapeutic usefulness clinically in combination with various antitumor drugs, if the selection of drugs combined with THP and the order of administration are suitable.

Topics: Animals; Antineoplastic Combined Chemotherapy Protocols; Cisplatin; Cyclophosphamide; Cytarabine; Doxorubicin; Drug Screening Assays, Antitumor; Fluorouracil; Leukemia P388; Male; Mercaptopurine; Methotrexate; Mice; Mice, Inbred BALB C; Mitomycin; Peplomycin; Vindesine

Aclacinomycin, isolated from the culture of a Streptomyces, and 4'-O-tetrahydropyranyladriamycin, prepared by chemical derivation, exhibit significantly low cardiac toxicity and more effectiveness than does adriamycin. Pepleomycin, a new derivative of bleomycin, has 4-5 times lower pulmonary toxicity and more potent activity than the parent antibiotic. The future prospects of studies on antibiotics with potential usefulness in treatment of lung cancer are discussed.

Topics: Aclarubicin; Adjuvants, Immunologic; Animals; Antibiotics, Antineoplastic; Bleomycin; Daunorubicin; Doxorubicin; Humans; Leukemia L1210; Lung; Lung Neoplasms; Mice; Molecular Weight; Naphthacenes; Peplomycin; Structure-Activity Relationship