peplomycin and Neoplasms

Optimal dose schedule of administration of antitumor antibiotics-bleomycin, adriamycin and aclacinomycin A-was reviewed from a point of view of pharmacokinetics. In case of bleomycin, according to its fast disappearance from blood, fast and significant excretion into urine, cell-cycle-dependent antitumor action, fast repair of potentially lethal damage, and pulmonary toxicity due to damage in endothelium of pulmonary capillary caused by high blood concentration of bleomycin, continuous intravenous administration seems to be a useful method to prevent pulmonary toxicity and to enhance antitumor effect. In case of adriamycin, according to its cardiotoxicity due to damage in cardiac muscle cell caused by high blood concentration on adriamycin, drip infusion or weekly low dose schedule is a safe, effective therapy to prevent cardiomyopathy. In case of aclacinomycin A, based on the mechanism of action of its marked inhibition in RNA synthesis compared to adriamycin, daily administration for certain days is an effective method.

Topics: Aclarubicin; Antibiotics, Antineoplastic; Bleomycin; Doxorubicin; Drug Administration Schedule; Humans; Infusions, Parenteral; Kinetics; Naphthacenes; Neoplasms; Peplomycin

Bleomycins are a group of glycopeptide antibiotics synthesized by Streptomyces verticillus that are widely used for the treatment of various neoplastic diseases. These antibiotics have the ability to chelate a metal center, mainly Fe(II), and cause site-specific DNA cleavage. Bleomycins are differentiated by their C-terminal regions. Although this antibiotic family is a successful course of treatment for some types of cancers, it is known to cause pulmonary fibrosis. Previous studies have identified that bleomycin-related pulmonary toxicity is linked to the C-terminal region of these drugs. This region has been shown to closely interact with DNA. We examined the binding of Zn(II)peplomycin and Zn(II)bleomycin-A

Topics: Antibiotics, Antineoplastic; Binding Sites; Bleomycin; DNA; Humans; Neoplasms; Nuclear Magnetic Resonance, Biomolecular; Peplomycin; Zinc

Topics: Antibiotics, Antineoplastic; Bleomycin; Dactinomycin; Humans; Mitomycin; Neoplasms; Peplomycin

To evaluate the feasibility of intraarterial infusion of microencapsulated anticancer drugs (chemoembolization), collective data on 1013 cancer patients were reviewed. Ethylcellulose microcapsules containing mitomycin C (median total dose 20 mg), cisplatin (60 mg) or peplomycin (40 mg) were given to tumor-feeding arteries by bolus infusion in 79% of the patients and by fractionated infusion in the others, as a palliative (71%) or preoperative measure (29%). The target sites were the liver (42%), kidney (24%), intrapelvic organs (18%), lung (4%), head and neck (3%), bone (1%) and others (9%), excluding the central nervous system and gastrointestinal tract. The incidence of overall adverse effects ranged from 0.2 to 54.9%, but grade 2-3 hematological, renal and hepatic toxicities, local pain, abdominal discomfort, cutaneous reaction, remote embolization and infection were < 10%. Nine patients (0.9%) in the early stages of trials suffered serious complications including treatment-related death in two with critical underlying diseases of the target organs. The remaining patients recovered from the adverse effects, except for grade 2 cutaneous reactions, within 2 months by routine palliative measures. A > or = 50% tumor reduction was seen in 28% of 427 evaluable tumors (42% for < 25-cm2 tumors and 20% for > or = 25-cm2 tumors) with a median treatment number of one. The response rate depended on both the tumor size and the treatment number (P < 0.05), but it was not affected by prior therapies. Mitomycin C microcapsules produced a higher response rate. Complete or partial remission of intractable pain and genitourinary gross hemorrhage was found in two-thirds of eligible patients. The results indicate that this treatment modality, though restricted by catheter technique, can be applied to various tumor lesions with an acceptable morbidity and prospective trials are justified to evaluate the potential role of such a targeted chemotherapy.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Antibiotics, Antineoplastic; Antineoplastic Combined Chemotherapy Protocols; Capsules; Chemoembolization, Therapeutic; Chemotherapy, Adjuvant; Cisplatin; Drug Administration Schedule; Feasibility Studies; Female; Humans; Infusions, Intra-Arterial; Japan; Male; Middle Aged; Mitomycin; Neoplasms; Palliative Care; Peplomycin; Retrospective Studies; Treatment Outcome

Peplomycin, derivative of Bleomycin which was developed because of a lower pulmonary toxicity and broader anti-tumor spectrum in animal study, also showed to be effective in clinical studies on adenocarcinomas such as prostatic cancer, breast cancer, etc. as well as on squamous cell carcinoma and the anti-tumor spectrum were observed to be broader than those of Bleomycin. Further, the combination therapy with other anti-cancer drugs showed higher effectiveness. Clinically lower pulmonary toxicity was also observed. Liblomycin, derivative of Bleomycin having a lipophyllic characteristics, was developed since it showed in animal studies a lower pulmonary toxicity than that of Peplomycin and broader anti-tumor spectrum. At present, this substance is under Phase I study in Japan.

Topics: Animals; Antibiotics, Antineoplastic; Antineoplastic Combined Chemotherapy Protocols; Bleomycin; Dogs; Humans; Methotrexate; Mice; Neoplasms; Neoplasms, Experimental; Peplomycin; Rats; Vincristine

Four kinds of cultured human tumor cell lines sensitive or resistant to bleomycin (BLM) were examined for the effect of filipin, a polyene antibiotic, on peplomycin (PEP)-induced cell killing. Although PEP was more effective than BLM against BLM-resistant HeLa cells (HeLa-BLMr), neoplastic cells derived from salivary gland (HSG) and melanoma cells (MEC), these three cell lines were still at least ten times more resistant to PEP than epidermoid carcinoma cell lines including HeLa cells by comparison of IC50, and showed lower cellular accumulation of 3H-PEP as compared with HeLa cells. When these lines were pretreated with filipin, 3H-PEP accumulation by the cells was increased 1.33-, 2.34-, 1.91- and 1.14-fold in HeLa, HeLa-BLMr, HSG and MEC cells, respectively. Combination use of PEP and filipin resulted in a remarkable enhancement of cytocidal effect in HeLa-BLMr and HSG cells (100- and 25-fold decrease of IC50, respectively), and a slight enhancement in HeLa cells, but not in MEC cells. It is therefore suggested that there are differences among cell types in the potentiation of PEP-induced cell killing by filipin.

Topics: Bleomycin; Cell Division; Cell Line; Cell Survival; Cells, Cultured; Drug Synergism; Filipin; HeLa Cells; Humans; Melanoma; Neoplasms; Peplomycin; Polyenes; Salivary Gland Neoplasms

In cancer therapy, the authors have attempted to decrease the side effects. Since 1975 they have used immuno-thermo-chemotherapy(so-called ITC therapy). At this time the ITC therapy is used in combination with induced-hypertension-chemotherapy (IHC therapy). This new approach has been applied to patients with terminal or advanced malignancy, which have been unsuccessfully treated by conventional ITC therapy. This report compares the clinical effects of conventional ITC therapy those of new modality in the same patient. The clinical results are 6 cases of I-A and one case of I-B according to Karnofsky's criteria. This New modality is more effective than the conventional ITC therapy in all 7 patients.

Topics: Angiotensin II; Antineoplastic Combined Chemotherapy Protocols; Bleomycin; Blood Pressure; Cisplatin; Cyclophosphamide; Doxorubicin; Female; Fluorouracil; Humans; Hyperthermia, Induced; Liver Neoplasms; Lung Neoplasms; Male; Middle Aged; Mitomycin; Mitomycins; Neoplasms; Peplomycin; Uterine Neoplasms; Vincristine

Five mg of peplomycin was administered continuously for 24 hours by intravenous or subcutaneous infusion. Subcutaneous administration of peplomycin was performed done with the use of an SP-5 microinfusion pump made by the in Nipro Company. The plasma concentration after intravenous infusion was 0.0106 +/- 0.039 microgram/ml, while that after subcutaneous infusion was 0.131 +/- 0.037 microgram/ml. There was no statistical significance between the differences observed for intravenous and subcutaneous infusion.

Topics: Antibiotics, Antineoplastic; Bleomycin; Esophageal Neoplasms; Female; Humans; Infusions, Parenteral; Lymphoma; Male; Neoplasms; Peplomycin; Prostatic Neoplasms

Selective arterial infusion of microencapsulated anticancer drugs has been introduced as an effective mode of targeted drug delivery system in cancer therapy. The potential therapeutic effect of this treatment comes from both the infraction and the sustained drug action, thus being described as CHEMOEMBOLIZATION. There is an increasing number of patients subjected to microcapsule therapy; during the recent 4 years, 285 patients with advanced carcinoma of the kidney, liver, urinary bladder, prostate and others including the GI tract, female genital organs, bone and lung were treated in 60 institutes of this country. Ninety percent of the patients received only single or duplicated infusion of the microcapsules with a mean dose of 21 mg. Of 211 measurable tumors, 74 (35%) showed a marked tumor reduction greater than 50%, 77 (37%) showed a moderate reduction less than 50% and 60 (28%) failed to respond. Intractable symptoms such as gross hemorrhage from the GU tract or severe pain were well controlled (75-81%). The remarkable antineoplastic effect of microcapsules often facilitated the radical surgery for highly invasive tumors and/or the organ preserving operation for locally invasive tumors. Additionally, a preoperative microcapsule therapy significantly improved 3 year survival rate of the patients with renal cell carcinoma, suggesting its usefulness as a preoperative adjuvant use. The results indicate that chemoembolization with microcapsules is an effective targeted cancer therapy for various organs.

Topics: Antibiotics, Antineoplastic; Bleomycin; Capsules; Female; Humans; Male; Mitomycin; Mitomycins; Neoplasms; Peplomycin; Prognosis

Topics: Adult; Aged; Antineoplastic Agents; Bleomycin; Drug Evaluation; Female; Humans; Male; Middle Aged; Neoplasms; Peplomycin

The blood lymphocyte population was monitored in 6 patients with advanced malignant tumors who were treated with large doses of a new cytotoxic drug termed pepleomycin. It was observed that the size of the cell population, its cellular composition, mitogen stimulations and natural killer activity did not change in any consistent ways during or after treatment. It is concluded that pepleomycin does not directly affect the lymphocytic population.

Topics: Adenocarcinoma; Adult; Aged; Antineoplastic Agents; Bleomycin; Female; Fibrosarcoma; Humans; Kidney Neoplasms; Killer Cells, Natural; Leiomyosarcoma; Leukocyte Count; Lymphocytes; Male; Middle Aged; Neoplasms; Peplomycin; Testicular Neoplasms; Thyroid Neoplasms