peplomycin and Kidney-Neoplasms

We have developed a new combination intravenous chemotherapy regimen called COMPA (IV-COMPA). The clinical value of IV-COMPA chemotherapy was evaluated based on the results of 24 patients with urothelial cancers. From October 1989 through October 1993, a total of 24 patients (20 males and 4 females) received IV-COMPA chemotherapy at Tokyo Medical College Hospital and Tokyo Medical College Hachioji Medical Center. All patients had advanced transitional cell carcinoma or adenocarcinoma of the urothelial tract (renal pelvis, ureter or bladder). One course of IV-COMPA was delivered at 2-week intervals and consisted of 30 mg/m2 CDDP on day 4 and 5, 0.6 mg/m2 VCR (Oncovin) on day 1 and 2, 5 mg/m2 MTX on day 2 and 3, 5 mg/m2 PEP on day 1, 2 and 3, 20 mg/m2 ADM on day 4. A few patients received the same regimen without peplomycin called IV-COMA to avoid pulmonary fibrosis. Fifteen patients with surgically confirmed invasive carcinoma were defined by at least 1 of the following criteria: multiple tumors or size greater than 5 cm, grade 3, stage P3 or P4, pN+, pR1, pL1, pV1, or secondary carcinoma in situ. These patients were treated with 2 or 3 corpses of postoperative IV-COMPA chemotherapy to improve prognosis. In this group, 14 of 15 (93%) are alive at a median follow-up of 22 months (range, 8-57 months) and actuarial survival rates of 1 and 3 years were 100%, 90.9%, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Adenocarcinoma; Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Carcinoma, Transitional Cell; Cisplatin; Doxorubicin; Drug Administration Schedule; Female; Humans; Infusions, Intravenous; Injections, Intramuscular; Kidney Neoplasms; Kidney Pelvis; Male; Methotrexate; Middle Aged; Peplomycin; Urinary Bladder Neoplasms; Vincristine

Topics: Adult; Aged; Bleomycin; Clinical Trials as Topic; Female; Humans; Kidney Neoplasms; Male; Middle Aged; Peplomycin; Prostatic Neoplasms; Suppositories; Urinary Bladder Neoplasms

A 69-year-old woman visited our hospital with complaints of low grade fever and general fatigue in October 1990. Computed tomography (CT), ultrasonogram, and renal arteriography showed left renal tumor and she was diagnosed with renal cell carcinoma (T2M0N0). Left radical nephrectomy was performed in December 12, 1990. After operation, 3 x 10(6) unit per day of IFN-alpha were administered three times per week. She complained of low grade fever and general fatigue in June, 1991. CT showed left lung metastasis (phi 3 cm). She was given combined chemotherapy (MVP: methotrexate, vinblastine, pepleomycin). After 2 courses, lung metastasis decreased and after 4 courses, lung metastasis was not shown by CT in December, 1992. No evidence of relapse was shown by CT in June, 1994.

Topics: Aged; Antineoplastic Combined Chemotherapy Protocols; Carcinoma, Renal Cell; Female; Humans; Kidney Neoplasms; Lung Neoplasms; Methotrexate; Peplomycin; Remission Induction; Vinblastine

We report a case of recurrent squamous cell carcinoma of the renal pelvis. A 61-year-old woman was readmitted to our hospital 4 months after left nephrectomy. The medical imaging method revealed a left retroperitoneal tumor and squamous cell carcinoma related antigen (SCC-Ag) elevated (82 ng/ml). We suspected a recurrent tumor from renal pelvic cancer. She received 2 courses of systemic chemotherapy with 5-FU and CDDP, but the tumor did not change. As a second treatment, combined radiotherapy with PEP was given. The tumor was reduced and SCC-Ag returned to the normal level. The patient is alive with no recurrence or metastasis at one year following these therapies.

Topics: Antineoplastic Combined Chemotherapy Protocols; Bleomycin; Carcinoma, Squamous Cell; Cisplatin; Drug Administration Schedule; Female; Fluorouracil; Humans; Infusions, Intravenous; Kidney Calculi; Kidney Neoplasms; Kidney Pelvis; Middle Aged; Neoplasm Recurrence, Local; Peplomycin

Selective intra-arterial infusion of ethylcellulose microcapsules containing anticancer drug exerts its therapeutic effects through infarction and sustained drug action (i.e., chemoembolization). Seven hundred and fifty-nine patients with malignant tumors of the liver (310), kidney (177), bladder (100), prostate (41), lung (39), pelvic organs (13), bone (4) and other (75) were treated with single or repeated chemoembolization using microcapsules delivered through percutaneous catheterization as a preoperative or palliative measure. Substantial tumor reduction of 50% was found in 18% of hepatoma, 19% renal cell carcinoma, 54% bladder carcinoma and 54% prostate carcinoma cases. Preoperative chemoembolization facilitated radical surgery for various cancers and significantly improved the survival of patients with locally invasive renal cell carcinoma and bladder carcinoma. Systemic toxic effects were mild, and all patients tolerated the treatment except for one who died of remote embolism to spleen and gallbladder. These results suggested that microcapsule chemoembolization can be successfully applied to a variety of tumors with low morbidity and mortality, and also combined with other treatments in multidisciplinary therapy.

Topics: Adolescent; Adult; Bleomycin; Capsules; Carcinoma, Hepatocellular; Carcinoma, Renal Cell; Cisplatin; Embolization, Therapeutic; Female; Humans; Kidney Neoplasms; Liver Neoplasms; Male; Middle Aged; Peplomycin; Prognosis; Prostatic Neoplasms; Urinary Bladder Neoplasms

The direct antitumor effects of combined administration of alpha-interferon and chemotherapeutic agents against the human tumor cell line derived from renal cell carcinoma were examined in vivo as xenograft in nude mice. The administration regimen was as follows: Human lymphoblastoid interferon (HLBI) was injected intramuscularly (1 x 10(5) IU/mouse/day) every day for 14 days. Peplomycin (PEP), adriamycin (ADM), or 5-fluorouracil (5-FU) was also administered at a dose of one third of their LD50. We evaluated the effect 20 days after initial administration using the ratio of mean tumor weight. Combined administration of HLBI and PEP or ADM was determined effective and inhibited tumor growth more strongly than HLBI alone or control. Furthermore, the histopathological examination suggested that the effect of combined administration was cytostatic rather than cytolytic.

Topics: Animals; Antineoplastic Agents; Bleomycin; Carcinoma, Renal Cell; Combined Modality Therapy; Doxorubicin; Female; Fluorouracil; Humans; Interferon Type I; Kidney Neoplasms; Mice; Mice, Nude; Neoplasm Transplantation; Peplomycin

Rats were treated for 1 week each with 0.05% N-butyl-N-(4-hydroxybutyl)nitrosamine (BBN), 0.2% N-bis(2-hydroxypropyl)-nitrosamine (DHPN) and 0.2% N-ethyl-N-hydroxyethylnitrosamine (EHEN) in the drinking water, and then administered diet containing 5% sodium L-ascorbate (Na-AsA), 1% butylated hydroxytoluene (BHT) or 0.05% phenobarbital (PB), or weekly intraperitoneal injections of 2 mg of pepleomycin per kg body weight until week 36. Histopathological examination revealed that all exerted significant modulation effects on tumor development in the various target organs. Na-AsA was found to inhibit liver but promote renal pelvis and bladder carcinogenesis. BHT similarly decreased liver and enhanced bladder lesion development. PB, in contrast promoted hepatocarcinogenesis. However both PB and BHT were associated with increased incidences of adenomas and adenocarcinomas of the thyroid. Thus the wide-spectrum initiation model allowed confirmation of site-specific modification potential and in addition demonstrated potentiation of kidney and bladder carcinogenesis promotion by pepleomycin.

Topics: Animals; Ascorbic Acid; Bleomycin; Body Weight; Butylated Hydroxytoluene; Cocarcinogenesis; Kidney Neoplasms; Liver Neoplasms; Lung Neoplasms; Male; Neoplasms, Experimental; Peplomycin; Phenobarbital; Rats; Rats, Inbred F344; Thyroid Neoplasms; Urinary Bladder Neoplasms

Two VPM-CisCF chemotherapy regimens (vincristine (VCR), peplomycin (PEP), methotrexate (MTX), cis-diamminedichloroplatinum (II) (CDDP), cytosine arabinoside (Ara-C) and 5-fluorouracil (5-FU), established using human bladder cancer xenografts in nude mice were applied for advanced urothelial cancer. VPM-CisCF (I) consisted of 0.4 mg/m2 VCR on days 1 and 4, 2 mg/m2 PEP on days 1-7, 2 mg/m2 MTX on days 2, 3, 5 and 6, 20 mg/m2 CDDP on days 8, 20 mg/m2 Ara-C on days 8 and 13, and 150 mg/m2 5-FU on days 10-12. VPM-CisCF (II) consisted of 0.6 mg/m2 VCR on days 1 and 3, 3 mg/m2 PEP on days 1-4, 3 mg/m2 MTX on days 2 and 3, 35 mg/m2 CDDP on day 4, 20 mg/m2 Ara-C on days 4 and 7, and 200 mg/m2 5-FU on days 5 and 6. These doses were adjusted for each case: the above mentioned dose x [(80/(40 + Age))2 + (Karnofsky's performance status/100)2]. VPM-CisCF (I) was administered to 6 patients (bladder cancer and transitional cell carcinoma), intra-arterially in two cases. One patient showed a complete response and survived for 7 months, three partial response (PR) surviving for 13, 8 and 37 (arterial-infused case) months, one showed minor response (MR) surviving for 4 months, and one had no change (NC) surviving for 5 months. VPM-CisCF (II) was administered to 11 patients (1 ureteral cancer, 1 renal pelvic cancer, 9 bladder cancer, and 10 transitional cell carcinoma except a case of mixed type of transitional cell carcinoma and squamous cell carcinoma). Four of the patients who had PR survived for 9, 8, 8 and 7 (alive) months, two who had MR survived for 8 and 4 months, three who had NC survived for 6, 4 and 4 months, and who two had progressive disease survived for 8 and 6 months. The major toxicities were myelosuppression and gastrointestinal symptoms, especially nausea and vomiting, but the treatment was well-tolerated.

Topics: Adult; Aged; Animals; Antineoplastic Combined Chemotherapy Protocols; Bleomycin; Carcinoma, Squamous Cell; Carcinoma, Transitional Cell; Cisplatin; Cytarabine; Female; Fluorouracil; Humans; Kidney Neoplasms; Male; Methotrexate; Mice; Mice, Nude; Middle Aged; Neoplasm Transplantation; Peplomycin; Ureteral Neoplasms; Urinary Bladder Neoplasms; Vincristine

Bleomycins (BLM) are widely used as antineoplastic agents either alone or in combination regimens. Results of earlier studies in experimental animals were said to be inadequate to evaluate the carcinogenicity of BLM, which is a known mutagen. In a dose-response study, BLM and peplomycin (PEP) were investigated in Sprague-Dawley rats of both sexes. For the first 10 weeks weekly doses of 0.35, 0.70, 1.40, and 2.80 mg/kg BLM and of 0.32, 0.63, 1.25, 2.50, and 5.0 mg/kg PEP were applied subcutaneously (BLM: 30 male and 30 female rats/group; PEP: 25 male and 25 female rats/group). In the case of BLM, thereafter the doses were given once every fortnight either for 1 year (BLM: 1.40 and 2.80) or for life (lower doses). In the case of PEP, application of the high doses was stopped after the 13th time (5.0: 10 X 1/week and 3 X 1 every 2 weeks) and the 19th application (2.5 mg: 10 X 1/week and 9 X 1/every 2 weeks). After the 10th dosing, the remaining groups were treated once every fortnight for life. 60 male and 60 female rats served as solvent-treated (physiological saline) controls. The animals were observed for life. Repeated doses of BLM and PEP reduced body weight and life expectancy of the animals in a dose-related pattern. Tubular cell damages and cell proliferations were seen as a symptom of major toxicity in the kidneys. In this model BLM and PEP are carcinogenic: treatments resulted in significant dose-related incidences of animals with tumors at the site of application (fibrosarcomas) and with renal tumors (adenomas, adenocarcinomas, sarcomas).

Topics: Animals; Antibiotics, Antineoplastic; Bleomycin; Body Weight; Carcinogens; Dose-Response Relationship, Drug; Female; Injections, Subcutaneous; Kidney Neoplasms; Male; Peplomycin; Rats; Risk; Sex Factors; Skin Neoplasms; Time Factors

In the search for bleomycin analogues with less pulmonary toxicity than bleomycin itself, peplomycin was selected for a phase I clinical trial, based on experimental animal data. Eighteen patients received peplomycin at three exploratory levels. Six patients were treated at a level of 5 mg/m2, 8 patients at 10 mg/m2 and 4 patients at 15 mg/m2 of peplomycin, each dosage being given twice weekly intravenously. Pulmonary function tests were performed prior to treatment and serially thereafter. Pulmonary toxicity was encountered when the administered total dose of peplomycin was in the range 190-350 mg in patients who had received either 10 or 15 mg/m2 twice weekly. Pulmonary toxicity was not observed when the dosage of peplomycin was restricted to 5 mg/m2 twice weekly. During the trial no haematological, hepatic or renal changes induced by the drug were observed. Skin changes, stomatitis and fever were observed with increasing frequency the higher the cumulative dose of peplomycin, and these effects were similar to those seen with bleomycin. Two of fifteen patients with cervical cancer obtained a partial response, lasting 1 and 2 months respectively. Although peplomycin is free from pulmonary toxicity at a dose of 5 mg/m2 twice weekly, the maximum tolerated cumulative dose has still to be defined.

Topics: Adult; Aged; Antibiotics, Antineoplastic; Bleomycin; Breast Neoplasms; Dose-Response Relationship, Drug; Drug Evaluation; Female; Humans; Kidney Neoplasms; Lung Diseases; Middle Aged; Ovarian Neoplasms; Peplomycin; Respiratory Function Tests; Skin Diseases; Uterine Cervical Neoplasms

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