peplomycin and Lung-Neoplasms

Both basal cell carcinoma (BCC) and squamous cell carcinoma (SCC) are very common in skin malignancy. Operative therapy is the first choice at the treatment for SCC and BCC in early stage. After excision for large skin tumor, occasionally we use skin flap or musculocutaneous flap or free flap. At the old patient of Stage III and IV SCC and BCC, sometimes reduction surgery is useful at the combination therapy. Radiation as adjuvant therapy is sometimes useful for not only SCC but also BCC. The clinical efficacy of CA (C' A') chemotherapy (CDDP, ADM or CBDCA, EPI-ADM), was evaluated on Stage III, IV SCC and BCC. The response rate was 63% in SCC and 75% in BCC.

Topics: Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Bleomycin; Carcinoma, Basal Cell; Carcinoma, Squamous Cell; Chemotherapy, Adjuvant; Cisplatin; Doxorubicin; Female; Humans; Lung Neoplasms; Lymph Node Excision; Male; Middle Aged; Palliative Care; Peplomycin; Prognosis; Radiotherapy, Adjuvant; Skin Neoplasms; Skin Transplantation; Surgical Flaps

The question of whether initial prognostic factors in small-cell lung cancer patients have a predictive value for patients' quality of life (QL) during chemotherapy is addressed in the context of a randomised clinical trial comparing early and late alternating chemotherapy (SAKK protocol 15/84). The relative impact of initial tumour stage and performance status, previous weight loss, sex and age on patient-rated QL was analysed over six chemotherapy cycles in 124-130 patients (according to available QL data) with more than 400 questionnaires. Fatigue/malaise, personal functioning, emotional and general well-being were prospectively selected as QL indicators. Predefined summary measures (average QL score over chemotherapy cycles, 'minimum', 'maximum' and 'final' improvement) were analysed separately by scale in various patient groups. General linear models adjusted for treatment arm and response were used to confirm the univariate findings. Within the overall sample, the average QL scores over six cycles were predicted by initial prognostic factors. Patients with poor prognostic factors reported worse QL. Within a limited sample (with baseline QL), patients with poor prognostic factors reported worse QL at baseline and greater improvement under treatment. Graphical comparison of QL patterns over cycles showed permanent discrimination by levels of prognostic factors. The impact of initial prognostic factors was consistently confirmed in the three analyses. Levels of performance status and weight loss best discriminated QL. Initial tumour stage, performance status and previous weight loss can predict QL in small-cell lung cancer during chemotherapy, even after controlling for response to treatment. Our results may contribute to clinical decision-making with regard to the intensity of chemotherapy and QL outcome, especially in patients with extensive disease.

Topics: Antineoplastic Combined Chemotherapy Protocols; Carcinoma, Small Cell; Cyclophosphamide; Female; Humans; Lomustine; Lung Neoplasms; Male; Methotrexate; Middle Aged; Nimustine; Peplomycin; Prognosis; Quality of Life; Vincristine

From November 1993 to December 1994, a prospective multi-centre phase II clinical trial was done in 137 patients with advanced cancer on China-made pepleomycin (PEP). PEP was effective in patients with cancer of the head and neck, malignant lymphmo and lung cancer, with response rate of 66.7%, 50% and 30%, respectively. The major adverse reactions were fever and mild gastrointestinal reaction. In the controlled study of combination chemotherapy with China-made and Japan-made PEP, the response rates and side effects were similar. The results indicate that China made PEP can be used in lieu of that made in Japan.

Topics: Adolescent; Adult; Aged; Antibiotics, Antineoplastic; Antineoplastic Combined Chemotherapy Protocols; Female; Head and Neck Neoplasms; Humans; Lung Neoplasms; Lymphoma; Male; Middle Aged; Peplomycin; Prospective Studies

The use of thoracic irradiation in the treatment of "limited disease" small-cell lung cancer yields better local control and survival rates than chemotherapy alone, according to meta-analysis studies of randomized clinical trials. Outside experimental studies, however, the role radiotherapy can currently play in the management of this type of cancer is difficult to assess because treatment modalities and patient selection criteria differ greatly. We report on the treatment outcome obtained in the Radiotherapy Department of the University of Siena in a series of 86 patients with small-cell lung cancer consecutively referred, January 1986 to January 1992; after a thorough staging, 46 of them were diagnosed as having a "limited disease". A "sequential" chemo-radiotherapy combination was used: irradiation was delivered after the completion of the initial drug treatment. Twenty-four patients (52.5%) achieved a complete and 22 (47.5%) a partial objective remission after chemotherapy, with acceptable early toxicity rates and severity. Twenty-eight of them received irradiation according to the following selection criteria: objective remission after chemotherapy (19 of 24 complete responders, excluding those with initial pleural effusion or worsening medical status during chemotherapy) and initial large tumor bulk (9 of 22 patients in partial remission). The overall treatment outcome rate (median survival: 18 months, 2-year survival: 28%) is in agreement with that of similar previous studies; toxicity rates are also similar (2% of treatment-related deaths). Survival analysis, according to "performance status" score, chemotherapy schedule and the achievement of complete remission with the initial drug management, exhibited significant differences only relative to the latter parameter. Many recent clinical trials suggest that combined chemo-radiotherapy could improve these results: toxicity is however reported as heavy, with this approach. Some guidelines are here considered, which could make this combination reliable also for current clinical use.

Topics: Aged; Antineoplastic Combined Chemotherapy Protocols; Bleomycin; Carcinoma, Small Cell; Cisplatin; Combined Modality Therapy; Etoposide; Female; Humans; Lung Neoplasms; Male; Middle Aged; Nimustine; Patient Selection; Peplomycin; Radiotherapy Dosage; Survival Rate; Time Factors; Treatment Outcome; Vinblastine; Vincristine

Eighty-six patients with non-small cell lung cancer who underwent curative operations were postoperatively randomized to control and adjuvant chemotherapy groups. In the adjuvant chemotherapy group, patients received cisplatin-based combination chemotherapy 3 or 4 weeks after operation and the average cycle of chemotherapy was 2.3 (from 1 to 6 cycles). In this trial, no evidence of improved survival or delayed recurrence was seen in the treated patients. In multivariate analysis of prognostic variables, the most important factor was the pathological stage of the disease and, second, DNA ploidy of the primary tumor. Although histology (squamous vs. non-squamous cell carcinoma) had a trend to influence the survival, it was not a significant factor. A total of 33 patients had recurrences: 17 and 16 patients were in control and adjuvant chemotherapy groups, respectively. Postrecurrent survival in the adjuvant chemotherapy group was significantly shorter than that in the control group, as determined by the generalized Wilcoxon and log rank tests. Median survival time after recurrence in the control and adjuvant therapy groups was 18.5 and 7.5 months, respectively. These results suggest that DNA ploidy of primary tumors should be considered as a prognostic factor in future trials of adjuvant therapy. Furthermore, analysis of postrecurrent survival in the adjuvant chemotherapy trial, as well as that of overall and disease-free survivals should be done.

Topics: Aged; Antineoplastic Combined Chemotherapy Protocols; Bleomycin; Carcinoma, Non-Small-Cell Lung; Carcinoma, Squamous Cell; Cisplatin; Combined Modality Therapy; Cyclophosphamide; DNA, Neoplasm; Doxorubicin; Female; Humans; Lung Neoplasms; Male; Middle Aged; Mitomycin; Mitomycins; Neoplasm Recurrence, Local; Neoplasm Staging; Peplomycin; Ploidies; Prognosis; Vindesine

We studied the efficacy of cisplatin-based polychemotherapy for non-small-cell lung cancer. One hundred nineteen patients with adenocarcinoma or large cell carcinoma were randomized to receive cyclophosphamide, adriamycin, cisplatin and mitomycin C (CAPM) or mitomycin C, cytosine arabinoside and tegafur (MCT), and 48 patients with squamous cell carcinoma were randomized to receive cisplatin, adriamycin and peplomycin (PAP) or mitomycin C, cyclophosphamide, tespamine, toyomycin and tegafur (MCTTT). Radiation was given to the chest in patients with stage I-III disease. The response rates were CAPM, 34.5%; MCT, 13.1% (p less than 0.01) and PAP, 63.3%; MCTTT, 42.3%. A significant difference in response rate between the CAPM and MCT regimens was observed only in stage IV patients and not in stage I-III patients. The median survival was 9.5 months in the CAPM arm vs. 6.5 months in the MCT arm (p less than 0.007), and 8.5 months in the PAP arm vs. 6.5 months in the MCTTT arm. Improved median survival for the CAPM regimen was noted only in stage IV patients and not in stage I-III patients when compared to patients given the MCT regimen, respectively. Nausea and vomiting were significantly increased in patients with cisplatin-based polychemotherapy. Myelosuppression was more severe with the CAPM regimen than with the other chemotherapy regimens. We concluded that cisplatin-based polychemotherapy, CAPM and PAP therapy were of more benefit to patients with disseminated non-small-cell lung cancer than MCT and MCTTT therapy.

Topics: Adult; Antineoplastic Combined Chemotherapy Protocols; Bleomycin; Bone Marrow; Carcinoma, Bronchogenic; Carcinoma, Non-Small-Cell Lung; Chromomycin A3; Cisplatin; Cyclophosphamide; Doxorubicin; Drug Administration Schedule; Female; Humans; Kidney; Lung Neoplasms; Male; Mitomycin; Mitomycins; Peplomycin

The prognostic significance of evaluation of response according to chest X-ray after only one cycle of treatment was investigated in patients with small cell lung cancer (SCLC). Three hundred and six patients entered a multicenter randomized German trial testing alternating vs. sequential chemotherapy. Decrease of tumor size after the first cycle was seen to be 78% in the alternating group and 70% in the sequential group. Stable disease occurred in 25% of the sequentially treated and 19% of the alternatingly treated patients. No substantial differences in pretreatment characteristics were noticed between patients with stable disease in sequential and alternating treatment. In sequential therapy, median survival was 323 days for patients with decrease of tumor size after the first cycle and 219 days for patients with no change. Only five out of 21 patients with no change after one cycle responded to continuous administration of this regimen including one complete remission. In alternating therapy, median survival was 347 days for patients with decrease in tumor size after the first cycle and 378 days for patients with no change indicating no difference in prognosis. Twelve out of 18 patients with no change responded to continuous administration of alternating treatment including six complete remissions. We concluded that response to the first cycle according to chest X-ray is a reliable and prognostically valid response criterion if sequential therapy is used. In this treatment modality no change in tumor size after the first cycle indicates poor prognosis, and improvement of the patients' outcome may be achieved by a switch to a second non-cross resistant drug combination.

Topics: Antineoplastic Combined Chemotherapy Protocols; Bleomycin; Carcinoma, Small Cell; Clinical Trials as Topic; Cyclophosphamide; Doxorubicin; Etoposide; Female; Humans; Ifosfamide; Lomustine; Lung Neoplasms; Male; Methotrexate; Nimustine; Nitrosourea Compounds; Peplomycin; Prognosis; Random Allocation; Vincristine; Vindesine

From March 1983 to February 1985, we treated 74 patients (pts) with inoperable non-small cell lung cancer. Twenty-seven pts with squamous cell carcinoma were randomized between regimen PMP (CDDP 60 mg/m2, d 1, MMC 6 mg/m2, d 3, d 10 and PEP 5 mg/m2, d 3-7) and regimen PM (CDDP 60 mg/m2, d 1 and MMC 6 mg/m2, d 3, d 10). Forty-seven pts with adenocarcinoma and large cell carcinoma were randomized between regimen PMF (CDDP 60 mg/m2, d 1, MMC 6 mg/m2, d 3, d 10 and FT 800 mg/body, d 3-21) and regimen PM. The response rates of evaluable cases (EC) were as follows: Squamous cell carcinoma; Regimen PMP 50% (1 CR + 4 PR/10 EC). Regimen PM 40% (4 PR/10 EC). Adenocarcinoma plus large cell carcinoma; Regimen PMF 13.6% (3 PR/22 EC). Regimen PM 11.1% (2 PR/18 EC). The median survival time (MST) was increased from 23 weeks in non-responders to 32 weeks in responders. However, the difference between the survival curves for responders and non-responders was not statistically significant. Of the toxic effects shown in all 74 registered pts, hematological (64.9%), gastrointestinal (60.8%) and renal (31.1%) toxicities were the common complications. We concluded that regimen PMP was more useful than regimen PM for pts with squamous cell carcinoma but that regimen PMF demonstrated no appreciable difference, compared with regimen PM for pts with adenocarcinoma and large cell carcinoma.

Topics: Adenocarcinoma; Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Bleomycin; Carcinoma, Non-Small-Cell Lung; Carcinoma, Squamous Cell; Cisplatin; Female; Humans; Lung Neoplasms; Male; Middle Aged; Mitomycin; Mitomycins; Peplomycin; Random Allocation; Tegafur

The effects of two chemotherapeutic regimens, peplomycin (PLM) plus carbazilquinone and PLM plus mitomycin, on non-small cell carcinoma of the lung were evaluated by a randomized controlled trial. Seven partial responses were observed in 53 evaluable patients, for an overall response rate of 13.2%. There was no difference in response rate or in median survival time between PLM plus carbazilquinone (11.5% and 32 weeks) and PLM plus mitomycin (14.8% and 25 weeks). Seven patients developed interstitial pneumonitis, and four died of pulmonary fibrosis. It was concluded that the chemotherapeutic regimens that include PLM are only marginally effective against non-small cell carcinoma of the lung, with relatively frequent pulmonary fibrosis.

Topics: Adenocarcinoma; Adult; Aged; Antibiotics, Antineoplastic; Azirines; Bleomycin; Carbazilquinone; Carcinoma, Small Cell; Carcinoma, Squamous Cell; Clinical Trials as Topic; Drug Therapy, Combination; Female; Humans; Lung Neoplasms; Male; Middle Aged; Mitomycins; Peplomycin; Random Allocation

Intraoperatively,the routine method to differentiate malignant lung neoplasms from benign lesions is by the judgment of naked eye or frozen section. It is not accurate to judge by naked eye and will take long time by frozen section. Using a gamma-detecting probe (GDP) to accurately detect the tumors and the metastases, the operators could decide the resection range and the treatment plan. This study was preliminary clinical practice of tumor imaging and radioimmunoguided surgery (RGS) using (99m)Tc-PPM (peplomycin) as a tumor tracer.. Thirty-seven patients were administered with injection of (99m)Tc-PPM. The images were taken preoperatively. Region of interest (ROI) method was performed and tumor-to- normal-tissue (T/NT) ratio was calculated on the image. The radioactivity of the specimens resected from the patients was detected using GDP at the time of surgery. T/NT ratio was obtained by comparing the radioactivity of the tumor tissue with the normal lung tissue.. The uptake ratios (T/NT) of (99m)Tc-PPM were different between malignant and benign lesion (P< 0.01). The ratio (T/NT, x+/-2s) was regarded as the threshold for differentiation of malignant and benign lesions. The sensitivity, specificity, and accuracy of identifying malignant lesion were 90%, 87.5%, and 89.3%, respectively; GDP could be used to accurately detect the invasive range of the tumors, with the sensitivity, specificity, and accuracy of identifying lymph node metastases of 91%, 88%, and 90%, respectively.. (99m)Tc-PPM is a useful agent in differentiating malignant lung neoplasm from benign lesions, and as a tumor tracer can be used in detecting tumor by GDP intraoperatively. The RGS is a simple method that can help the surgeon in the intraoperative assessment of the tumor and the lymph node metastases.

Topics: Adult; Aged; Antibiotics, Antineoplastic; Female; Gamma Rays; Humans; Lung Neoplasms; Male; Middle Aged; Peplomycin; Radionuclide Imaging; Technetium

A 31-year-old man was admitted to our hospital with the chief complaint of painful right scrotal swelling. Based on the diagnosis of right testicular tumor with multiple lung metastasis and L2 vertebral body metastasis, right high orchiectomy and three courses of chemotherapy (peplomycin, etoposide, CDDP) were performed. Histological diagnosis was teratocarcinoma. With the complete remission for lung metastasis and no change for bone metastasis, L2 spondylectomy and additional four courses of the same chemotherapy were performed. The patient has been free of the disease for 11 months after the spondylectomy.

Topics: Adult; Antineoplastic Combined Chemotherapy Protocols; Cisplatin; Combined Modality Therapy; Disease-Free Survival; Etoposide; Humans; Lumbar Vertebrae; Lung Neoplasms; Male; Orchiectomy; Peplomycin; Spinal Neoplasms; Teratocarcinoma; Testicular Neoplasms

Although hyperthermia potentiates the effect of radiation, the combined effect decreases as the time between irradiation and hyperthermia increases. The purpose of this study was to prevent the rapid loss of efficacy by the local injection of epinephrine or peplomycin(PEP), two agents known as hyperthermic potentiators. In this study, Lewis lung carcinoma implanted in the foot of BDF1 mice was used for the assessment of tumor growth, skin reactions, and lung metastasis. The tumors were irradiated, then warmed in a water bath for 45 min. The retarding effects of hyperthermia on tumor growth and skin reactions were lost 2 days after irradiation. However, when PEP or epinephrine was injected before hyperthermia, tumor growth was distinctly delayed. The effect of epinephrine was greater than PEP and still showed enhancement 8 days after irradiation. For skin reactions, no significant enhancing effect was observed. Lung metastasis was significantly inhibited by the addition of epinephrine either 0 or 2 days after irradiation. In conclusion, the local administration of epinephrine combined with hyperthermia significantly retarded tumor growth without an increase in skin reactions or lung metastases. Possible mechanism underlying this phenomenon was discussed.

Topics: Animals; Carcinoma, Lewis Lung; Combined Modality Therapy; Epinephrine; Female; Foot; Hyperthermia, Induced; Lung Neoplasms; Mice; Neoplasm Transplantation; Peplomycin; Skin

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

Since 1989, 4 patients with Stage III nonseminomatous germ cell tumor of the testis underwent thoracotomy for persistent radiographic masses after systemic chemotherapy. They were treated with multi-drug regimen including cisplatin, vincristine, methotrexate, peplomycin, and etoposide until normalization of tumor markers was obtained. Residual masses of the 4 patients consisted of viable cancer cells in 1 patient, immature teratoma in 1, mature teratoma in 1 and necrosis in 1. Of the 4 patients 3 achieved complete remission and are doing well with no evidence of disease, while the other case with residual viable cancer cells died of renal failure. The key to successful treatment of advanced testicular cancer was considered to be a favorable response to chemotherapy and complete resection of any residual tumors.

Topics: Adult; Antineoplastic Combined Chemotherapy Protocols; Bleomycin; Chemotherapy, Adjuvant; Cisplatin; Drug Administration Schedule; Etoposide; Germinoma; Humans; Lung Neoplasms; Lymphatic Metastasis; Male; Methotrexate; Peplomycin; Testicular Neoplasms; Thoracotomy; Vincristine

A case of metastatic infantile yolk sac tumor of testis is reported herein. The patient was 23 months old with a painless swelling of the right scrotal contents. Histological examination revealed yolk sac tumor. Six months later, the serum alpha-fetoprotein (AFP) was re-elevated and solitary lung metastasis had developed. After 4 courses of chemotherapy with cisplatin (CDDP), vincristine (VCR), methotrexate (MTX), peplomycin (PEP) and Etoposide (COMPE), serum AFP was normalized and lung metastasis disappeared. He has shown no evidence of disease for 5 years with normal physical growth. Aggressive chemotherapy including CDDP might be used for Stage III infantile testicular cancer.

Topics: Antineoplastic Combined Chemotherapy Protocols; Bleomycin; Cisplatin; Endodermal Sinus Tumor; Etoposide; Humans; Infant; Lung Neoplasms; Male; Methotrexate; Peplomycin; Remission Induction; Testicular Neoplasms; Vincristine

In Japan the regimen with peplomycin has been mainly used for the treatment of squamous cell carcinoma (SCC). But recently, a regimen with cisplatin, particularly the combination of cisplatin and adriamycin (CA chemotherapy) has been used for the treatment of SCC, and a better prognosis has resulted Since CA chemotherapy is very effective for not only SCC, but also basal cell carcinoma (BCC), we think it is a prominent neoadjuvant therapy for SCC and BCC. We have used CA chemotherapy for multiple lung metastasis of BCC over the past six years, and three times PR was obtained, with survival so far.

Topics: Adult; Aged; Aged, 80 and over; Antineoplastic Combined Chemotherapy Protocols; Bleomycin; Carcinoma, Basal Cell; Carcinoma, Squamous Cell; Chemotherapy, Adjuvant; Cisplatin; Doxorubicin; Drug Administration Schedule; Female; Humans; Lung Neoplasms; Lymphatic Metastasis; Male; Middle Aged; Peplomycin; Skin Neoplasms

A 32-year-old Japanese male consulted a clinic complaining of gynecomastia. Right painless scrotal swelling was also detected. Right high orchiectomy was performed, then the surgical specimen was histopathologically confirmed as choriocarcinoma and mature teratoma. The imaging revealed cerebral, pulmonary, retroperitoneal metastases. After 3 courses of combination chemotherapy with cisplatin, etoposide and peplomycin (PEP therapy), the brain metastasis completely disappeared and the serum titer of the tumor markers such as beta-HCG became normal. The regression rates of lung and retroperitoneal metastases were 68% and 27%, respectively. Therefore, retroperitoneal lymph node dissection was performed. After the 5th course of PEP therapy, lung metastases disappeared completely. Until the present, no evidence of disease has persisted. The PEP therapy, which is a salvage therapy for refractory testicular cancer, was performed as first-line chemotherapy in this case. It was an excellent modality against choriocarcinoma, along with the surgical treatment.

Topics: Adult; Antineoplastic Combined Chemotherapy Protocols; Bleomycin; Brain Neoplasms; Chemotherapy, Adjuvant; Choriocarcinoma; Cisplatin; Etoposide; Humans; Lung Neoplasms; Lymph Node Excision; Male; Neoplasms, Multiple Primary; Orchiectomy; Peplomycin; Remission Induction; Retroperitoneal Neoplasms; Teratoma; Testicular Neoplasms

A 77-year-old man with recurrent lung cancer was administered peplomycin (PEP) 15 mg 1A only one time, from a link in the chain of chemotherapy. But just after it was occurred dyspnea, and heard crepitus by auscultation. And it was recognized of ground glass appearance and air-bronchogram in the entire lung field by chest X-ray photograph, so made a diagnosis of acute diffuse interstitial pneumonia by clinical. He died two days after in spite of emergency treatment, that is high dose steroid, O2 flow etc. We discussed the acute pulmonary side effect of peplomycin which is one of the carcinostatic antibiotic, according to this clinical progress.

Topics: Aged; Bleomycin; Carcinoma, Squamous Cell; Humans; Infusions, Intravenous; Lung Neoplasms; Male; Neoplasm Recurrence, Local; Peplomycin; Pulmonary Fibrosis

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

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

Chemotherapy with bronchial artery infusion (BAI) was given to 34 patients with primary lung cancer. Treatment regimens usually employed cis-diammine-dichloroplatinum (CDDP) plus peplomycin for squamous cell carcinoma, and CDDP plus vindesine for adenocarcinoma. The provisional therapeutic effects were evaluated roentgenographically with reference to histological type, T factor and degree of vascularization. Out of 10 cases of squamous cell carcinoma, 7 cases (70%) showed tumor regression greater than 50%, in contrast to 4 of 17 cases (23.5%) of adenocarcinoma. The effects in cases of squamous cell carcinoma were correlated with tumor vascularity. Twenty-two surgically treated cases were examined for the histological effects of BAI. Five of 6 cases (83.3%) of squamous cell carcinoma showed IIb effects by Shimosato's criteria. These results showed that the therapeutic effect of BAI was excellent in cases of squamous cell carcinoma in comparison with cases of adenocarcinoma. Serious side effects including esophago-bronchial fistula, massive hemoptysis and esophageal ulcer were observed in 4 cases.

Topics: Adenocarcinoma; Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Bleomycin; Carcinoma, Small Cell; Carcinoma, Squamous Cell; Cisplatin; Doxorubicin; Drug Administration Schedule; Female; Fluorouracil; Humans; Lung Neoplasms; Male; Middle Aged; Mitomycin; Mitomycins; Peplomycin; Vindesine

A patient with large cell carcinoma of the lung with multiple intrapulmonary metastases has been treated with three courses of cisplatin-based polychemotherapy (cisplatin, adriamycin and peplomycin). He experienced nausea, vomiting, alopecia, and bone marrow suppression as side effects, which proved to be mild, that he tolerated well. A complete response was obtained, and he has been free of disease for more than three years.

Topics: Adult; Antineoplastic Combined Chemotherapy Protocols; Bleomycin; Carcinoma, Small Cell; Cisplatin; Doxorubicin; Humans; Lung Neoplasms; Male; Peplomycin; Remission Induction

Topics: Aged; Antineoplastic Combined Chemotherapy Protocols; Bleomycin; Bronchial Arteries; Carcinoma, Non-Small-Cell Lung; Cisplatin; Combined Modality Therapy; Female; Humans; Infusions, Intra-Arterial; Lung Neoplasms; Male; Middle Aged; Mitomycin; Mitomycins; Peplomycin; Radiotherapy Dosage; Vindesine

Topics: Bleomycin; Female; Humans; Lipid Peroxides; Lung Neoplasms; Male; Peplomycin; Peptide Fragments; Peptidyl-Dipeptidase A; Phospholipids; Procollagen; Pulmonary Fibrosis; Radiotherapy; Testicular Neoplasms

Topics: Adenocarcinoma; Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Bleomycin; Bronchial Arteries; Carcinoma, Small Cell; Carcinoma, Squamous Cell; Cisplatin; Doxorubicin; Female; Humans; Infusions, Intra-Arterial; Lung Neoplasms; Male; Middle Aged; Mitomycins; Peplomycin; Vincristine

Topics: Aclarubicin; Aged; Antineoplastic Combined Chemotherapy Protocols; Bleomycin; Bronchoalveolar Lavage Fluid; Bronchopneumonia; Carcinoma, Small Cell; Carcinoma, Squamous Cell; Cisplatin; Cyclophosphamide; Doxorubicin; Humans; Lung; Lung Neoplasms; Male; Methotrexate; Middle Aged; Peplomycin; Vincristine

Advanced squamous cell carcinoma of the head and neck, lung, esophagus, and uterine cervix is still a challenging cancer to the medical practice. We have treated 23 such patients with a combination of cis-platinum, vincristine, and peplomycin. Cis-platinum was given at a dose of 60 mg/m2 on day 1, and 1.0 mg/m2 of vincristine was given on day 3, followed 6 hours later by peplomycin 10 mg/day by continuous infusion iv or sc over the next 5 days. This combination was given every 3 weeks. The overall response rate was 71% for 17 evaluable patients, including one complete response. The median duration of response and survival was 2 and 5 months, respectively. Six other patients with esophageal and cervical carcinoma were treated with two cycles of this combination followed by radical radiation therapy or surgery. Five of them achieved significant response prior to radical treatment. Major side effects were nausea, vomiting, alopecia, and mild myelotoxicity, which were acceptable. This regimen, with a high response rate and acceptable toxicity, warrants further investigation.

Topics: Adult; Antibiotics, Antineoplastic; Antineoplastic Combined Chemotherapy Protocols; Bleomycin; Carcinoma, Squamous Cell; Cisplatin; Combined Modality Therapy; Drug Evaluation; Esophageal Neoplasms; Female; Head and Neck Neoplasms; Humans; Lung Neoplasms; Neoplasm Recurrence, Local; Peplomycin; Time Factors; Uterine Cervical Neoplasms; Vincristine

Based on the cell types in bronchogenic carcinoma, we treated 123 patients with different regimens of combination chemotherapy. The chemotherapy regimens consisted of CAP (cyclophosphamide + adriamycin + platinum) for 60 patients with adenocarcinoma and large cell carcinoma, PP (peplomycin + platinum) for 29 patients with squamous cell carcinoma and CAV (cyclophosphamide + adriamycin + vincristine) for 35 patients with small cell carcinoma. These regimens were repeated every 4 weeks for at least 2 cycles. The response rates for CAP, PP and CAV were 18.3% (11 PR), 20.7% (6 PR) and 60% (10 CR + 11 PR), respectively. Median survival time (MST) was 12.5 months for CAP, 8.5 months for PP and 9.5 months for CAV. Responders had a significantly (P less than 0.002) improved survival (MST, 15.5 months) compared to non-responders (MST, 7.5 months) in small cell carcinoma. However, there was no significant difference between responders and non-responders in CAP and PP. Survival of patients with PS 0-1 was significantly better than that with PS 2-3 in all treated patients. Nausea and vomiting were severe in patients treated with platinum-based polychemotherapy. There was no renal failure although a transient increase of serum creatinine was noted in CAP and PP. Myelosuppression was mild to moderate in all patients treated with CAP, PP and CAV.

Topics: Adenocarcinoma; Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Bleomycin; Carcinoma, Bronchogenic; Carcinoma, Small Cell; Carcinoma, Squamous Cell; Cisplatin; Cyclophosphamide; Doxorubicin; Female; Humans; Lung Neoplasms; Male; Middle Aged; Peplomycin; Peptichemio; Vincristine

The effect of PPM therapy, consisting of cisplatin, peplomycin and mitomycin C, was evaluated in 15 cases of squamous cell lung cancer. Ten partial responses were achieved in primary cases and the response rate was 66.7%. Nephrotoxicity was well controlled with a continuous infused drip and FOM. The nausea and vomiting were reasonably well controlled with methylprednisolone and metoclopramide. Severe interstitial pneumonitis occurred in 5 cases (33.3%). PPM therapy is considered to be a very useful combination chemotherapy for squamous cell lung cancer but careful attention must be paid to pulmonary toxicity.

Topics: Aged; Antibiotics, Antineoplastic; Antineoplastic Combined Chemotherapy Protocols; Bleomycin; Carcinoma, Squamous Cell; Cisplatin; Drug Administration Schedule; Female; Humans; Infusions, Parenteral; Isotonic Solutions; Lung Neoplasms; Male; Methylprednisolone; Metoclopramide; Middle Aged; Mitomycin; Mitomycins; Nausea; Peplomycin; Ringer's Lactate

A 38-year-old man was admitted to Nara Medical University Hospital on Feb.7,1983, because of swelling of the scrotal contents on the right side and elevated serum AFP, beta-HCG and LDH suggestive of testicular tumor. Right orchiectomy was carried out and a pathological diagnosis of embryonal cell carcinoma of the right testis (pT3N0M1) was made. The patient, upon evidence of multiple pulmonary metastases, was treated with a combination chemotherapy of cis-Diamminedichloroplatinum, vincristine and peplomycin. After three courses of combination chemotherapy, pulmonary metastases were decreased, but their foci persisted. The patient was then treated with Etoposide 62 mg/m2 daily for 5 days every three weeks, and after this course, complete remission of pulmonary metastases was obtained. The patient recieved 3 courses of Etoposide and retroperitoneal lymph node dissection, and has since shown no evidence of disease for 2 years and 4 months after surgery.

Topics: Adult; Antineoplastic Combined Chemotherapy Protocols; Bleomycin; Cisplatin; Combined Modality Therapy; Drug Administration Schedule; Etoposide; Humans; Lung Neoplasms; Lymph Node Excision; Male; Peplomycin; Podophyllotoxin; Teratoma; Testicular Neoplasms; Vincristine

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

The relationship between morphological manifestations and cell kinetic changes of three lung cancer cell lines after exposure with chemotherapeutic agents was studied. After treatment with Cis-dichloro diammine platinum (II) (CDDP), an increase in cells of G2/M compartment at first, and then of S compartment was observed. As for the morphological manifestation, enlarged nuclear cells were more frequently observed. These cells seemed to be in S-G2/M compartment and to die finally. However a part of cells escaped from complete blockade may show multiple nuclei. Also after treatment with Etoposide (VP-16), an increase of G2/M compartment was observed, and on the morphological manifestation enlarged nuclear cells or double-or multiple-nuclear cells were observed. As these cells seemed to enter into G2/M compartment immediately. Cell destruction was thought to be started earlier compared with other two drugs. After treatment with Peplomycin (PEP), its effects on cell cycle traverse were only minimum accumulation of G2/M compartment in high PEP concentration. However concerning the morphological manifestation, many cells treated with PEP revealed enlarged, double or multiple nuclei. This suggests that morphological manifestation may reflect cytocydal effects more dominantly than cell cycle traverse. Each chemotherapeutic agent influenced the morphological manifestation and the cell kinetics of human lung cancer cells characteristically. It seemed to be important to study these relations in order to estimate the effect of chemotherapeutic agents and the therapeutic efficacy on cancer cells.

Topics: Adenocarcinoma; Antineoplastic Agents; Bleomycin; Carcinoma, Small Cell; Carcinoma, Squamous Cell; Cell Cycle; Cell Line; Cisplatin; DNA, Neoplasm; Etoposide; Flow Cytometry; Humans; Lung Neoplasms; Peplomycin

Topics: Aged; Bleomycin; Humans; Infusions, Parenteral; Lung; Lung Neoplasms; Male; Middle Aged; Peplomycin; Prostatic Neoplasms

Topics: Aged; Bleomycin; Carcinoma, Squamous Cell; Humans; Lung Neoplasms; Male; Peplomycin; Pulmonary Fibrosis

Advances in the treatment of inoperable non-small cell lung cancer (NSCLC) have been falling behind the recent results obtained for small cell lung cancer (SCLC) which had been considered the more malignant type with the shortest survival time. Recently, however, with the introduction of cisplatin, the results of combination chemotherapy for NSCLC have shown a degree of advancement so that an average response rate of 40% and a median survival time (MST) of 8-10 months can be obtained. Our method of combination chemotherapy, PPM (cisplatin, peplomycin, mitomycin C), resulted in an overall response rate of 44% (40% squamous, 29% adeno, 64% large) and an MST of more than 23.3 months in responders. With PFM (cisplatin, 5FU, mitomycin C), response rate was 35% and an MST of 18.7 months was obtained for adenocarcinoma responders. It can therefore be said that we have achieved a new degree of success in the treatment in NSCLC.

Topics: Adenocarcinoma; Antineoplastic Combined Chemotherapy Protocols; Bleomycin; Carcinoma, Small Cell; Carcinoma, Squamous Cell; Cisplatin; Drug Administration Schedule; Fluorouracil; Humans; Lung Neoplasms; Mitomycin; Mitomycins; Peplomycin

Effects of BAI therapy on 86 cases of lung cancer were evaluated in three groups: single-use of MMC group after intravenous PEP administration (PEP (iv).MMC group), PEP and MMC combination use group (PEP + MMC group) and single use of MMC group. Tumor regression rate determined by chest X-ray film 2 or 3 weeks after BAI was highest in the PEP (iv).MMC group followed by the PEP + MMC and MMC group. Cavity formation was more typical in the group treated with PEP + MMC. Histopathological effects were best for the PEP + MMC group followed by those of the PEP (iv).MMC and MMC group. As for side effects, pulmonary fibrosis and necrotizing bronchitis were noted in 8% of the PEP + MMC group, but side effects in the other two groups were mild. In conclusion single use of MMC after intravenous PEP administration was found to be the best way to give BAI in these three groups.

Topics: Adenocarcinoma; Bleomycin; Bronchial Arteries; Carcinoma, Small Cell; Carcinoma, Squamous Cell; Humans; Infusions, Intra-Arterial; Lung Neoplasms; Mitomycin; Mitomycins; Peplomycin

Twelve patients with unresectable and recurrent non-small cell carcinoma of the lung were treated with a combination chemotherapy consisting of cis-platinum and adriamycin. The overall response rate was 42% with two complete responses and three partial responses. The durations of response were 9+ and 8.5+ months in two complete responses, and 7.5+, 5.5+ and 2.5 months in three partial responses. The overall median survival was 8 months ranging 3.5+ to 16+ months. Three patients had leukopenia less than 2,000/mm3, two patients had thrombocytopenia less than 100 X 10(3)/mm3, and four patients had hemoglobin decrease of 3 g/dl or more. Severe nausea occurred in nine patients, whereas vomiting did in seven patients. Nearly total alopecia was observed in all patients. Renal toxicity in four patients was also observed, but was reversible. We believe that the combination chemotherapy with cis-platinum and adriamycin is promising in the management of patients with non-small cell carcinoma of the lung.

Topics: Adenocarcinoma; Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Bleomycin; Carcinoma, Squamous Cell; Cisplatin; Doxorubicin; Female; Humans; Lung Neoplasms; Male; Middle Aged; Mitomycin; Mitomycins; Peplomycin

Six patients with recurrent carcinoma of the uterine cervix were treated with a combination of peplomycin, adriamycin and cis-platinum (PAP). The PAP regimen consisted of peplomycin at a dose of 5 mg/day, continuous i.v. drip on days 1-7, adriamycin at a dose of 40 mg/m2 i.v. on day 1, and cis-platinum at a dose of 40 mg/m2, continuous i.v. drip on day 1, repeating at five to six week intervals. Three complete responses and three partial responses were obtained in six evaluable patients. Toxicities included mild to moderate nausea and vomiting, alopecia, nephrotoxicity, and myelosuppression, were generally manageable. We have concluded that PAP regimen is one of the useful regimens for recurrent uterine cervical carcinoma with pulmonary metastasis.

Topics: Adult; Antineoplastic Combined Chemotherapy Protocols; Bleomycin; Carcinoma, Squamous Cell; Cisplatin; Doxorubicin; Female; Humans; Lung Neoplasms; Middle Aged; Neoplasm Recurrence, Local; Peplomycin; Uterine Cervical Neoplasms

The nutritional and immune status were studied in advanced lung cancer patients receiving combined chemotherapy and an elemental diet to test the effectiveness of the latter. Parameters such as skin tests, lymphocyte count, total protein and albumin values, body weight, and nitrogen balance were improved or maintained by the administration of the elemental diet. A better response to chemotherapy was achieved in patients receiving the elemental diet. Elemental diet support is suggested as a useful addition to chemotherapy in advanced lung cancer.

Topics: Antineoplastic Combined Chemotherapy Protocols; Bleomycin; Blood Proteins; Cisplatin; Doxorubicin; Humans; Lung Neoplasms; Mitomycin; Mitomycins; Parenteral Nutrition; Parenteral Nutrition, Total; Peplomycin; Serum Albumin; Skin Tests

The application of a heat pad in the hyperthermia treatment of malignant skin tumors was examined. The temperature on the skin surface, and at a depth of 1 mm and 2 mm became 42C, 41C and 40C respectively, and was maintained for 4 hours. Two patients were treated with the heat pad alone, four were treated in combination with radiotherapy and one patient each with Pepleomycin injection and Bleomycin ointment. Irrespective of the above methods used, the heat pad was effective.

Topics: Adult; Aged; Bleomycin; Breast Neoplasms; Combined Modality Therapy; Female; Hot Temperature; Humans; Lung Neoplasms; Male; Middle Aged; Ointments; Peplomycin; Picibanil; Skin Neoplasms; Skin Temperature

The serum carcinoembryonic antigens (CEA) levels in 177 advanced lung cancer patients were studied to assess their value for the prognosis and indicating the effectiveness of chemotherapy. The relationship of pretreatment CEA levels with histology and stage of disease was also examined. Levels in excess of 5 ng/ml and 20 ng/ml were found in 55% and 32% of lung cancer patients, respectively. The elevated CEA levels were more frequently observed in patients with adenocarcinoma (65% in excess of 5 ng/ml) and extensive disease, but pretreatment CEA levels were not significantly correlated with the histology and clinical stage of disease. In 102 patients with adenocarcinoma, there was no significant difference of survival time in each patient with CEA levels less than 5 ng/ml, 5.0 less than or equal to - less than 20 ng/ml and in excess of 20 ng/ml; median survival time was 7, 7, 8 mo, respectively, and response to chemotherapy was not significant in each of these groups. Serial serum CEA measurements in patients with pretreatment levels in excess of 20 ng/ml correlated well with changes in disease status reflecting clinical response to chemotherapy. Mean percent changes of CEA levels to pretreatment levels were-77.4% in patients with partial response (PR), -55.6% in those with minor response (MR), -4.0% in patients with no change (NC) and +79.0% in patients showing progressive disease (PD). There was a significant difference in the percent changes of CEA levels between patients with an objective response (PR) and patients who had none (MR + NC) (p less than 0.02). CEA levels of all patients who had PD increased or unchanged. Serial measurements of serum CEA are useful in patients whose pretreatment levels are more than 20 ng/ml for monitoring the response to chemotherapy, and may be a useful noninvasive technique for patients with unmeasurable disease as a monitor of tumor burden in response to chemotherapy and recurrent disease.

Topics: Adenocarcinoma; Antineoplastic Combined Chemotherapy Protocols; Bleomycin; Carbazilquinone; Carcinoembryonic Antigen; Carcinoma, Small Cell; Carcinoma, Squamous Cell; Cisplatin; Cyclophosphamide; Humans; Lung Neoplasms; Mitomycin; Mitomycins; Nimustine; Nitrosourea Compounds; Peplomycin; Vinblastine; Vincristine; Vindesine

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

Pneumonitis-fibrosis which was induced by the treatment with antineoplastic agent(s) and/or irradiation was encountered in 37 (14.1%) of a total of 515 patients with lung cancer who had been treated in our institute during a period of seven years from 1976 through 1982. Of 251 patients who had been treated with bleomycin or pepleomycin alone or in combination with other antineoplastic agent(s) or irradiation, 46 (18.3%) had pneumonitis-fibrosis and 19 (7.6%) died therefrom. It was revealed that the patients over 50 years of age, whose PaO2 and % VC prior to the treatment with bleomycin were less than 79 mmHg and 79% respectively appeared to be predisposed to bleomycin pulmonary toxicity. Most of the pneumonitis which developed in these patients was progressive and fatal. Daily oral administration of 10 mg of prednisolone was in effective for the prevention of bleomycin-induced pneumonitis-fibrosis. A sudden decrease of PaO2 and a sharp elevation at a certain point in time during treatment were indicative of the fatal outcome of toxic pulmonary complications. Thoracic irradiation prior to, concomitant with or after bleomycin therapy enhanced the pulmonary toxicity of bleomycin. Therefore, combination therapy should be avoided. A continuous intravenous infusion may be the most effective and least toxic method to administer bleomycin.

Topics: Adenocarcinoma; Antibiotics, Antineoplastic; Bleomycin; Carcinoma, Small Cell; Carcinoma, Squamous Cell; Female; Humans; Lung Neoplasms; Male; Peplomycin; Prognosis; Pulmonary Fibrosis

The effect and toxicities of Cis-containing combination chemotherapy were tested in 28 patients with primary lung cancer. All patients were treated with 80 mg/m2 Cisplatinum on the first day and 750 mg ftorafur p.o. every day. In addition to these drugs, patients with squamous cell cancer were treated with continuous subcutaneous infusion of 4 mg/m2 Peplomycin for 5 days and one shot i.v. of 4 mg MMC. Patients with adeno- and large cell cancer were treated with 30 mg/m2 Adriamycin and 4 mg MMC, while patients with small cell cancer were given 150 mg/m2 VP-16 p.o. for 5 days. The following results were obtained. Of 22 evaluable patients, overall response rate was 50%. In each histologic type, response rate was 50% (5/10) for squamous cell carcinoma 50% (4/8) for adenocarcinoma 33% (1/3) for large cell carcinoma and 100% (1/1) for small cell carcinoma. No CR was obtained in this series. Main side effects due to Cisplatinum were nausea, vomiting, loss of appetite, mild leukopenia and thrombocytopenia, mild elevation of serum creatinine and BUN and alopecia, all of which were transient. Interstitial pneumonitis was observed in 40% of patients with squamous cell cancer. Two patients with adenocarcinoma died within 3 weeks after treatment due to embolism of the abdominal aorta and myocardial infarction probably caused by treatment with Adriamycin.

Topics: Adenocarcinoma; Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Bleomycin; Carcinoma, Small Cell; Carcinoma, Squamous Cell; Cisplatin; Doxorubicin; Drug Administration Schedule; Female; Humans; Lung Neoplasms; Male; Middle Aged; Mitomycin; Mitomycins; Peplomycin; Tegafur

Twenty patients with unresectable non-small cell lung cancer were treated with a combination chemotherapy of cisplatin (30 mg/body i.v., days 1-5), peplomycin (5 or 8 mg/body continuous infusion, days 1-5), mitomycin C (4 mg/body i.v., day 1), and vincristine (2 mg/body i.v., day 1), of 15 patients evaluable for response (9 with squamous cell carcinoma, 2 with adenocarcinoma, nd 4 with large cell carcinoma), the overall response rate was 46.7% with 7 partial responses. The median survival period for responders. Toxicity included hair loss, nausea and/or vomiting, mild to moderate myelosuppression, nephrotoxicity, and pulmonary toxicity, all of which was manageable. This four-drug combination chemotherapy is concluded to be effective for non-small cell lung cancer.

Topics: Adenocarcinoma; Aged; Antineoplastic Combined Chemotherapy Protocols; Bleomycin; Carcinoma, Small Cell; Carcinoma, Squamous Cell; Cisplatin; Female; Humans; Lung Neoplasms; Male; Middle Aged; Mitomycin; Mitomycins; Peplomycin; Vincristine

A phase II trial has been performed in squamous cell carcinoma of the lung using peplomycin. This compound is a bleomycin analogue with less pulmonary toxicity and a broader antitumor effect than bleomycin in experimental animal systems. Twenty-one evaluable patients were treated using a dose schedule of 5 mg/m2 twice weekly intravenously. None of the patients had previously received radiation or chemotherapy. The median dose of peplomycin received was 160 mg (range 45-254). One patient obtained a partial remission lasting 3 months. One out of 21 patients developed clinical symptoms and a decrease in the lung function test performed during treatment indicative of toxicity. Other manifestations of toxicity are comparable to those of bleomycin.

Topics: Aged; Antibiotics, Antineoplastic; Bleomycin; Carcinoma, Squamous Cell; Drug Evaluation; Humans; Lung Neoplasms; Middle Aged; Peplomycin

Twelve patients with recurrent breast cancer were treated with Peplomycin monotherapy. Peplomycin was given intermittently with a dose of 10 mg intramuscularly twice a week. As side effects of Peplomycin, fever elevation in 75% (9/12), malaise in 67%, nausea and vomiting in 42%, anorexia in 42%, pulmonary toxicity in 8%, and loss of hair in 8%, were observed. Out of 8 evaluable cases, CR was obtained in 1, PR in 1, NC in 3, and PD in 3 cases, respectively.

Topics: Adult; Aged; Antibiotics, Antineoplastic; Bleomycin; Breast Neoplasms; Carcinoma, Intraductal, Noninfiltrating; Carcinoma, Papillary; Drug Evaluation; Female; Humans; Lung Neoplasms; Middle Aged; Neoplasm Metastasis; Neoplasm Recurrence, Local; Peplomycin

Effects of BAI with PEP 30 mg+MMC 10 mg on 26 patients with lung cancer were evaluated in comparison with 34 cases treated with single PEP or MMC. Histopathological findings of the cases treated with PEP+MMC and PEP alone showed more effective results than that of MMC alone. The tumor decreased rate on the chest X-ray film of the cases treated with PEP+MMC was highest and the cavity formation was also typical in the cases with PEP+MMC and PEP alone. The side effects of the cases with PEP+MMC were able to reduce markedly to about 50% compared with single administration of PEP or MMC; however pulmonary fibrosis and necrotizing bronchitis were noted in 8%.

Topics: Antibiotics, Antineoplastic; Bleomycin; Bronchial Arteries; Drug Therapy, Combination; Humans; Infusions, Intra-Arterial; Lung Neoplasms; Lymphatic Metastasis; Mitomycin; Mitomycins; Peplomycin

Chemotherapy regimens containing pepleomycin, a derivative of bleomycin, were used for 81 patients with advanced primary lung cancer and 32 patients with metastatic pulmonary tumors. Among the patients with non-small cell carcinoma of the lung, partial responses were observed in three of 27 patients treated with pepleomycin + carbazilquinone and four of 26 patients treated with pepleomycin + mitomycin C (published in Cancer Treatment Reports, 1983). Five partial responses (primary organ: larynx, esophagus, lung, pancreas and uterus; one patient each) in 23 evaluable patients with metastatic pulmonary tumors were observed during treatment, for an overall response rate of 21.7%. In patients with primary lung cancer, no correlation between the incidence of the decrease in partial arterial oxygen tension (PaO2) during treatment and age was observed. Decrease in PaO2 during treatment was found more frequently in patients with abnormal pulmonary function before treatment than in patients with normal pulmonary function, but the mean lowest values of PaO2 in the two groups were the same. Intravenous weekly injection of pepleomycin is less likely to result in a decrease in PaO2 than two daily intramuscular injections. Definite pulmonary toxicity occurred in seven of the 113 patients (6.2%). Each of the seven received a total dose of over 60 mg and their ages were over 60 yr, although no correlation between the incidence of pulmonary fibrosis and total cumulative dose of pepleomycin was observed. Six of the seven patients died of pulmonary fibrosis in spite of prednisone treatment. Clinical, radiologic and histopathologic findings associated with pepleomycin were the same as those of bleomycin pulmonary toxicity. Further studies are needed to determine the appropriate dose schedule and route of administration of pepleomycin with regard to its benefit and toxicity.

Topics: Age Factors; Aged; Antibiotics, Antineoplastic; Bleomycin; Carbazilquinone; Drug Therapy, Combination; Humans; Lung; Lung Neoplasms; Middle Aged; Oxygen; Peplomycin; Prednisone; Pulmonary Fibrosis

Topics: Adenocarcinoma; Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Bleomycin; Carcinoma, Small Cell; Carcinoma, Squamous Cell; Cisplatin; Female; Humans; Lung Neoplasms; Male; Middle Aged; Mitomycin; Mitomycins; Peplomycin

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

The effect of chemotherapy on natural killer (NK) activity and antibody-dependent cell-mediated cytotoxicity (ADCC) in 15 advanced carcinomas of the lung was examined with regard to the drug, dose, route and timing of administration. The relationship between the effect of chemotherapy on the prognosis for the patients, and the changes in NK activity and ADCC, was also analysed. The NK activity and ADCC in patients with poor prognosis were significantly subnormal, even before treatment. The NK activity and ADCC began to decrease 2 weeks after the initiation of treatment and reached the lowest level during the 3rd or 4th week in all patients. Thereafter, they returned to the pretreatment level in 8 patients with stabilized disease. In contrast, they were not restored in 7 patients with progressive disease and poor prognosis. In 4 patients it was found that the effect of chemotherapy with pepleomycin and carbazilquinone on NK activity and ADCC differed according to the drug used. From this pilot study it is suggested that NK activity and ADCC are valuable prognostic factors in patients with advanced carcinoma of the lung, and that detailed analysis of the effect of each anticancer agent on NK activity and ADCC is desirable for the establishment of better treatment regimens for advanced carcinoma of the lung.

Topics: Aged; Antibiotics, Antineoplastic; Antibody-Dependent Cell Cytotoxicity; Azirines; Bleomycin; Carbazilquinone; Female; Humans; Killer Cells, Natural; Lung Neoplasms; Male; Middle Aged; Neoplasm Staging; Peplomycin; Pilot Projects; Prognosis; Time Factors

Eighteen previously untreated patients with squamous cell carcinoma of the lung were treated with a combination of a new bleomycin derivative, peplomycin and esquinon (PQ). One patient achieved a complete response (5.5%) and 5 patients a partial response (27.8%). Overall response rate was 33.3%. Median survival time of 6 patients with complete and partial response was 54 weeks and that of 12 patients with no change and progressive disease was 15 weeks. Toxicities included nausea and/or vomiting in 89%, fever in 61%, interstitial pneumonitis in 28% and leukopenia in 17%. PQ regimen appears to be effective in the treatment of squamous cell carcinoma of the lung.

Topics: Aged; Antibiotics, Antineoplastic; Azirines; Bleomycin; Carbazilquinone; Carcinoma, Squamous Cell; Drug Therapy, Combination; Female; Humans; Lung Neoplasms; Male; Middle Aged; Peplomycin

(1) Therapeutic effects of bronchial artery infusion (BAI) of peplomycin (PEP), a derivative of bleomycin, were examined in the 13 patients with lung cancer. The effectiveness of PEP was compared with that of 59 patients treated with mitomycin (MMC) or carboquon (CQ). (2) In all cases treated with PEP, histopathological effects revealed to be more than grade IIa of Shimosato's criteria, which were more effective than that with MMC or CQ. (3) Histopathological changes of the metastatic lymph nodes were similar to that of the main tumor. (4) In the cases treated with PEP, tumor decreased rates shown in the chest X-ray films 2 weeks after BAI were lower than that with MMC or CQ. Cavity formation in the tumor was recognized in 62% of the cases treated with PEP. (5) Low fever lasting several days after administration of BAI and GI symptoms such as nausea and vomiting were main side effects, which were mild and not so serious.

Topics: Adenocarcinoma; Azirines; Bleomycin; Bronchial Arteries; Carbazilquinone; Carcinoma, Small Cell; Carcinoma, Squamous Cell; Humans; Infusions, Intra-Arterial; Lung Neoplasms; Mitomycins; Peplomycin

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

Topics: Adenocarcinoma; Aged; Antibiotics, Antineoplastic; Bleomycin; Carcinoma; Carcinoma, Squamous Cell; Drug Therapy, Combination; Female; Humans; Lung; Lung Neoplasms; Male; Middle Aged; Peplomycin