peplomycin and Melanoma

At present, the chemotherapeutic combinations for melanoma available are three regimens using DAV, PAV and CDV. Among of them, the DAV combination (dacarbazine, ACNU, vincristine) and PAV (peplomycin, ACNU, vincristine) are used as post-operative adjuvant therapy for stage II and III patients. Their aim is to prevent recurrence and prolong survival. For stage IV patients, the major therapeutic procedure is a CDV combination (cisplatin, dacarbazine, vindesine). Adoptive immunotherapy is almost always used for patients with distant metastases. They have shown comparable effects for metastatic lesion in the lymph nodes, mucous membrane, brain and lung. Excellent results were obtained in patients having skin metastases by intratumoral injection of interferon-beta. Studies on new drugs and their combinations must be undertaken for more effective treatment of malignant melanoma.

Topics: Antineoplastic Combined Chemotherapy Protocols; Bleomycin; Chemotherapy, Adjuvant; Cisplatin; Dacarbazine; Humans; Immunotherapy, Adoptive; Melanoma; Neoplasm Metastasis; Nimustine; Peplomycin; Vincristine

A study of combination chemotherapy with nitrosomethylurea, vincristine and peplomycin or bleomycetin given an 5-6-day cycles showed the cytotoxic regimens to be more effective than single-agent treatment with dacarbazine for disseminated melanoma of the skin with metastases to the subcutaneous fat, lymph nodes, lungs and other viscera. In a group of 129 such patients, complete (12%) and partial remission (38%) was observed with the former combination whereas with nitrosomethylurea, vincristine and bleomycetin, complete and partial response rates were 7.6 and 26.9%, respectively.

Topics: Adolescent; Adult; Aged; Antibiotics, Antineoplastic; Antineoplastic Combined Chemotherapy Protocols; Bleomycin; Female; Humans; Male; Melanoma; Methylnitrosourea; Middle Aged; Neoplasm Recurrence, Local; Peplomycin; Prospective Studies; Remission Induction; Skin Neoplasms; Vincristine

Malignant melanoma is among the malignant tumors which still have the poorest prognosis. Thus, malignant melanoma of stage II and the more advanced stages. At present, chemotherapeutic combinations used as the first choice in Japan are two regimens of postoperative adjuvant therapy for stage II and III patients, that aim at preventing recurrence. One of the regimens is a DAV combination (Dacarbazine, ACNU, vincristine), and another is PAV combination (Pepleomycin, ACNU, vincristine). For stage IV patients, the major therapeutic procedure is a CDV combination (cisplatin, dacarbazine, vindesine). The efficacy of CDV treatment has been approximately 30 per cent in our studies. It has shown comparable effects for metastatic lesion in the lymph nodes, mucous membrane (nasal cavity) and brain, while lesions in other organs are largely unaffected in many instances. Studies of new drugs and combinations must be undertaken for the treatment of malignant melanoma.

Topics: Antineoplastic Combined Chemotherapy Protocols; Bleomycin; Cisplatin; Dacarbazine; Drug Administration Schedule; Female; Humans; Melanoma; Middle Aged; Nimustine; Peplomycin; Skin Neoplasms; Vincristine

Tumor cells derived from 13 different individual human tumors were plated in a colony forming monolayer assay. The effect of bleomycin and peplomycin on colony formation was assessed in normothermic conditions and after a hyperthermic treatment at 40.5 degrees C for 2 h at the beginning of the culture. In three out of the 13 tumor samples (two colon carcinomas, one malignant melanoma), hyperthermic incubation resulted in a thermal enhancement of the effects of bleomycin and peplomycin. In addition, human bone marrow progenitor cells (CFU-C) were subjected to the same procedure. Peplomycin proved to be less toxic to CFU-C than bleomycin. In samples from eight different donors, homogeneous dose-response curves were observed. There was no difference between normo- and hyperthermic incubation.

Topics: Bleomycin; Cell Survival; Colonic Neoplasms; Colony-Forming Units Assay; Dose-Response Relationship, Drug; Gallbladder Neoplasms; Hematopoietic Stem Cells; Hot Temperature; Humans; Lung Neoplasms; Melanoma; Myosarcoma; Neoplastic Stem Cells; Peplomycin; Tumor Stem Cell Assay

Topics: Animals; Bleomycin; Combined Modality Therapy; Hyperthermia, Induced; Male; Melanoma; Mice; Mice, Inbred BALB C; Mice, Nude; Neoplasm Transplantation; Peplomycin; Skin Neoplasms

A 76-year-old woman visited us with the chief complaint of a urethral mass on September 11, 1984. There was a thumb-sized, brownish and painless mass in the posterior wall of the urethra. Although excretory urogram revealed nothing remarkable, CT scan suggested metastasis of retroperitoneal lymph nodes. Biopsy of the urethral mass revealed malignant melanoma. She was treated with combined chemotherapy of dimethyltriazenoimidazole carboxamide, peplomycin, and cis-diamine-dichloride platinum, but died of respiratory insufficiency on January 6, 1985. Thirteen cases of primary malignant melanoma of the female urethra, including our own, have been reported in the Japanese literature.

Topics: Aged; Antineoplastic Combined Chemotherapy Protocols; Bleomycin; Cisplatin; Combined Modality Therapy; Dacarbazine; Female; Humans; Melanoma; Peplomycin; Urethral Neoplasms

Cases of maxillary cancer treated at our institute can be divided into two groups. In the first group (1971-1982, N = 85), we treated maxillary cancer by preoperative intraarterial infusion of 5-FU and Linac X-ray irradiation (60 Gy/6 weeks), followed by maxillectomy. In the second group (1982-1986, N = 32), we further combined intraarterial or intravenous chemotherapy using CDDP preoperatively or postoperatively depending upon the stage of the cancer. Five-year survival rate was 64.7% in the first group and 73.9% in the second. In the first group, the most frequent cause of death was distant metastasis without local recurrence. In the second group, the histopathological effect of chemotherapy and radiotherapy was improved with a reduced frequency of distant metastasis and it has now become possible to have 5-year survivors from among N2 and M1 cases. Judging from the histopathological effects of chemotherapy and radiotherapy, it seems possible to treat T2 and some T3 cases of maxillary cancer without performing maxillectomy. However, in T4 and most of T3 cases in which early recurrence is difficult to detect, it seems safer to combine total maxillectomy primarily.

Topics: Adenocarcinoma; Aged; Antineoplastic Combined Chemotherapy Protocols; Bleomycin; Carcinoma, Squamous Cell; Cisplatin; Combined Modality Therapy; Female; Humans; Injections, Intra-Arterial; Lymphatic Metastasis; Male; Maxillary Neoplasms; Melanoma; Middle Aged; Peplomycin

The cytotoxic effect of bleomycin and peplomycin was compared using a methylcellulose monolayer assay for the cultivation of human tumor cells. In 3 out of 4 samples from human malignant melanomas peplomycin proved to be more cytotoxic than bleomycin. Peplomycin was more cytotoxic than bleomycin in 1 of 5 myosarcoma samples, whereas 2 samples from squamous cell carcinomas of the lung showed identical dose response curves. In 1 carcinoma of the gall bladder peplomycin was more toxic than bleomycin.

Topics: Bleomycin; Cells, Cultured; Colonic Neoplasms; Colony-Forming Units Assay; Dose-Response Relationship, Drug; Humans; Lung Neoplasms; Melanoma; Myosarcoma; Peplomycin; Tumor Stem Cell Assay; Urinary Bladder Neoplasms

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

Malignant melanoma is one of the most malignant froms of cancer, for which the prognosis is still very grave. However, it need not necessarily be regarded as such a fearful tumor if it is found at an early stage and treated thoroughly and adequately. An understanding of the early clinical changes in the size, color and shape of the tumor is required, and early discovery can save a patient's life. Histopathological examination should be done for diagnosis, and S-100 protein should be checked together with monoclonal antibody studies sometimes. The main principle of treatment in the early stage of malignant melanoma is to make an incision 2 to 5 cm away from the edge of the tumor. As a rule, exploratory excision and minor resection should not be performed. It may be said, accordingly, that multidisciplinary treatment should only be given for malignant melanoma of stage 1b and more advanced stages. At present, chemotherapeutic combinations used as the first choice in Japan are two regimens, one of which is DAV (DTIC, ACNU and vincristine), and the other, PAV (peplomycin, ACNU and vincristine). The effectiveness rate with DAV and PAV have been approximately 30% in various clinical studies. Favorable clinical responses obtained by radiotherapy have often been observed after fast neutron irradiation and hyperthermia therapy. Immunotherapy and interferon treatment are also often applied for malignant melanoma.

Topics: Antineoplastic Combined Chemotherapy Protocols; Bleomycin; Combined Modality Therapy; Dacarbazine; Humans; Lymph Node Excision; Melanoma; Nimustine; Nitrosourea Compounds; Peplomycin; Prognosis; Skin; Skin Neoplasms; Vincristine

The combined effect of cryosurgery and anticancer drugs (cryochemotherapy) was studied in an experimental B16 melanoma/BDF1 tumor system. Vascular volume and vascular permeability after cryosurgery of normal skin and the tumor were measured by using 51Cr-labeled red blood cells and 125I-labeled serum albumin. The vascular volume and vascular permeability of both the normal vessels and the tumor vessels greatly increased immediately after cryosurgery, and their vascular volume decreased to less than the normal level within a few hours. However, the tumor vessels showed less dilatation and increase in permeability than the vessels of normal tissue. There was a difference in functional characteristics in response to cryoinjury between the normal vessels and the tumor vessels. The anticancer drugs, peplomycin and adriamycin, were administered intraperitoneally in combination with cryosurgery. When peplomycin was administered 5 min, 1 hr, and 3 hr after cryosurgery, the drug concentration in the frozen tumor was higher than that in the untreated tumor. But when administered 1 hr before cryosurgery, peplomycin was not trapped in the tumor. Trapping of adriamycin was not observed after the same treatment. In cryochemotherapy, it is necessary to administer the appropriate drug at the appropriate time. However, the trapping of the anticancer drug results in a high concentration and lasts for a long time, so that cryochemotherapy is expected to be a new mode of cancer therapy, particularly as a multidisciplinary treatment for cancer.

Topics: Animals; Antineoplastic Agents; Bleomycin; Cell Line; Combined Modality Therapy; Cryosurgery; Dacarbazine; Doxorubicin; Female; Melanoma; Mice; Peplomycin

By continuous infusion of angiotensin II, a marked increase in blood flow can be induced in tumour tissues, with no increase in normal tissues. This functional characteristic of tumour blood vessels, i.e., lack of autoregulation, has been utilized as an aid to chemotherapy by selectively enhancing drug delivery to tumour tissues. We describe our results in seven patients with malignant melanoma.

Topics: Adult; Aged; Angiotensin II; Antineoplastic Combined Chemotherapy Protocols; Bleomycin; Blood Flow Velocity; Dacarbazine; Female; Humans; Male; Melanoma; Middle Aged; Peplomycin; Vincristine

Topics: Adenocarcinoma; Bleomycin; Carcinoma, Squamous Cell; Cisplatin; Female; Genital Neoplasms, Female; Humans; Melanoma; Peplomycin; Tumor Stem Cell Assay

Topics: Animals; Bleomycin; Humans; Male; Melanoma; Mice; Neoplasms, Experimental; Peplomycin; Prostatic Neoplasms

The pulmonary toxicity and antitumor activity of a new bleomycin analog butylamino-3-propylamino-3-propylamine (Blm-BAPP) was investigated and compared with bleomycin and pepleomycin. Blm-BAPP was significantly more pulmonary toxic than bleomycin and had no greater activity against B16 melanoma than either bleomycin or pepleomycin. Although pepleomycin was as equitoxic as bleomycin in producing pulmonary fibrosis, doses of pepleomycin greater than 5 mg/kg were more lethal than bleomycin. Not only did the three drugs function similarly in vivo, but they behaved similarly in two in vitro test systems: microsome-catalyzed drug-mediated DNA deoxyribose cleavage and binding to DNA.

Topics: Animals; Bleomycin; Drug Interactions; Hydroxyproline; Lung; Male; Melanoma; Mice; Microsomes; Peplomycin

A combination chemotherapy (PAV) consisting of peplomycin, ACNU and vincristine (VCR) was given to 30 patients with malignant melanoma and its therapeutic evaluation was performed. The objective response rate was 42.9% for the patients with stage IV metastatic lesions; three of 7 patients showed improvement. This regimen was particularly effective for both cutaneous and subcutaneous metastatic lesions. When PAV was applied as an adjuvant therapy to the operable cases with stage Ib and II, a five-year survival rate was 50% and the result was far better than that of operation alone. Our results in PAV regimen almost identical with those of DAV(DTIC, ACNU, and VCR) regimen as an adjuvant therapy. The result indicates that PAV regimen is useful for the treatment of malignant melanoma since toxic reactions were mild. Further studies are necessary to assess the efficacy of PAV regimen.

Topics: Adult; Antineoplastic Combined Chemotherapy Protocols; Bleomycin; Drug Administration Schedule; Female; Humans; Melanoma; Nimustine; Nitrosourea Compounds; Peplomycin; Skin Neoplasms; Vincristine

Therapeutic effects of PEP-AC and PEP-saline on pulmonary growth of intratracheally implanted tumor and metastasis into the hilar lymph nodes were studied in mice. Pharmacokinetic studies of PEP-AC and PEP-saline were made by autoradiography (ARG) using 3H-PEP and microbial assay method using B. subtilis. The ARG using 3H-PEP-AC and 3H-PEP-saline demonstrated qualitatively slower elimination of PEP-AC from mouse lung than that of PEP-saline. The half-life time (t1/2) of PEP-AC was estimated to be about 3 days by bioassay method, while about 60 min. was given for PEP-saline. Intratracheal administration of PEP-saline produced no therapeutic effect to pulmonary growth of B16 melanoma, while that of PEP-AC gave a good response depending on doses. Furthermore, PEP-AC inhibited metastasis of B16 melanoma into the hilar lymph nodes. Better therapeutic effects were produced by PEP-AC when decreased inoculum sizes of B16 melanoma or P388 leukemia cells were transplanted.

Topics: Adsorption; Animals; Antibiotics, Antineoplastic; Bleomycin; Charcoal; Isotonic Solutions; Lung Neoplasms; Male; Melanoma; Mice; Mice, Inbred C57BL; Mice, Inbred DBA; Neoplasms, Experimental; Peplomycin

1. The therapeutic effects of pepleomycin seem superior to those achieved with bleomycin against squamous cell carcinoma and malignant lymphoma. 2. In basal cell epithelioma, carcinoma in situ (e.g., actinic keratosis, Bowen's disease), adenocarcinoma (e.g., mammary and genital Paget's disease), and adult soft tissue sarcoma, pepleomycin as well as bleomycin was clinically ineffective. 3. Of the two cases of stage IV malignant melanoma, pepleomycin combined with MeCCNU and VCR exerted a moderate effect against multiple disseminated skin metastases in one, and a slight effect against a VI rib metastasis in the other. 4. The sorts of side effects of pepleomycin were almost the same as those of bleomycin. Lung toxicities were less frequent under pepleomycin treatment than those under bleomycin treatment.

Topics: Adolescent; Adult; Aged; Antineoplastic Agents; Bleomycin; Carcinoma, Squamous Cell; Drug Evaluation; Female; Humans; Japan; Lymphoma; Male; Melanoma; Middle Aged; Peplomycin; Skin Neoplasms