peplomycin and Esophageal-Neoplasms

Pepleo-jelly, peplomycin (PEP) compounded with sodium polyacrylate (PANa), was used as a local preoperative chemotherapy for esophageal cancer. Thirty milligrams of PEP emulsified in 10 ml of jelly was orally administered for 17 patients on consecutive bed time, and the average total dose was 470 mg. Concentrations of PEP in blood and tissue were measured with a bioassay. PEP was not detected in the blood but was detected in esophageal tissue and regional lymphnodes. A significant difference (p less than 0.05) of tissue concentrations between normal esophageal mucosa (0.11 microgram/g) and malignant region (0.34 microgram/g) was noted. Furthermore, PEP was detected in many regional lymphnodes. Histological antitumor effect (Ef2) was noted in three of the eight metastatic lymphnodes. A side effect of this treatment was not recognized. It is believed that this treatment is safe and useful in combination with other adjuvant cancer therapy.

Topics: Acrylic Resins; Administration, Oral; Adult; Aged; Aged, 80 and over; Antineoplastic Agents; Bleomycin; Esophageal Neoplasms; Female; Humans; Male; Middle Aged; Peplomycin; Preoperative Care

Topics: Aged; Antineoplastic Combined Chemotherapy Protocols; Bleomycin; Carcinoma, Squamous Cell; Cisplatin; Combined Modality Therapy; Esophageal Neoplasms; Evaluation Studies as Topic; Female; Humans; Male; Methotrexate; Middle Aged; Peplomycin; Remission Induction

Between 1985 and 1990, 20 patients with stage 2 and 3 esophageal cancer without esophagopulmonary fistulas were treated with alternating radiotherapy and chemotherapy (cisplatin, methotrexate, and peplomycin). Patients given the combined therapy received courses of chemotherapy during weeks 1 and 6 and radiotherapy during weeks 2-5 and 7-9. Chemotherapy consisted of i.v. cisplatin (80 mg/ m2 of body surface area) on day 1, i.v. methotrexate (40 mg/ m2) on day 2, and s.c. peplomycin (10 mg/day) continuously from day 2 to day 5. Radiotherapy was external irradiation with or without intracavitary irradiation. In seven cases, external irradiation alone was administered at 65-70 Gy, and in 13 cases, external irradiation (50-55 Gy) was combined with intracavitary irradiation (14-20 Gy). At the end of treatment, the rate of complete response was 60% with an overall response rate of 95%. Five-year total survival was 25%; cause-specific survival was 36.8%. The most common acute toxicities were bone marrow suppression, hepatic and renal damage, pneumonitis, and esophagitis. There was no life-threatening toxicity.

Topics: Aged; Antineoplastic Combined Chemotherapy Protocols; Carcinoma, Squamous Cell; Cisplatin; Disease-Free Survival; Esophageal Neoplasms; Female; Humans; Male; Methotrexate; Middle Aged; Peplomycin; Prospective Studies; Radiotherapy Dosage

A new dosage formulation consisting of anticancer drugs bound to carbon particles was developed for treating cancers of the upper digestive tract, and is designed to distribute higher levels of anticancer drug to the regional lymph nodes and at the injection site, as compared to a drug in aqueous solution form. Thirteen patients with histologically proven carcinoma (8 with superficial esophageal cancer and 5 with early or proper muscle layer-infiltrating gastric cancer), in whom surgical treatment was contraindicated, received intra- and peritumoral injection of the new dosage formulation (total dose of 35-100 mg of peplomycin or 250-500 mg of methotrexate) guided by esophago- or gastro-fiberscope. Eleven of these 13 patients are currently alive, 12-64 months after therapy, or they died without evidence of recurrence 12-98 months after the treatment. One patient has remained cancer-free for 37 months after a second course of the therapy given to treat a recurrence found 26 months after the first treatment. Another patient has a recurrent tumor 9 months after the therapy and is now going to undergo a second course of treatment. Side effects were not severe and well-tolerable.

Topics: Adenocarcinoma; Antineoplastic Combined Chemotherapy Protocols; Carbon; Carcinoma, Squamous Cell; Endoscopy, Digestive System; Esophageal Neoplasms; Humans; Injections, Intralesional; Lymphatic Metastasis; Methotrexate; Peplomycin; Prognosis; Stomach Neoplasms; Treatment Outcome

According to the data obtained from the fundamental investigations using flow cytometry we designed the schedule of combination chemotherapy for solid cancer patients and we tried this therapy on 25 patients with non-curative, unresectable and recurrent cancers: 9 gastric, 5 colo-rectal, 3 esophageal, 3 pancreatic, 2 gall bladder, 2 lung and 1 breast cancer. The treatment was performed every 3 or 4 weeks as follows: CDDP 70 mg/m2 (d.i.), PEP 4 mg/m2 (i.v.) and MMC 4 mg/m2 (i.v.) on day 1, ADM 15 mg/m2 (i.v.) on day 4, and 5-Fu 250 mg/body (d.i.) every day. Among 22 patients evaluated completely, 1 complete response, 9 partial responses, 11 no changes, 1 progressive disease were obtained. The overall response rate was 45%. From the comparison of survival curves, survival rate was significantly better in patients responded to this therapy than in patients who did not respond to it (p less than 0.05). As for side effects, myelosuppression occurred in 19 patients (86%), increase of BUN and/or creatinine were observed in 3 patients (14%), increase of GOT and/or GPT were seen in 10 patients (45%), gastrointestinal symptoms and alopecia were observed in almost all patients, but all of these toxicity were transient and did not impede the continuous treatment.

Topics: Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Bleomycin; Cisplatin; Colorectal Neoplasms; Doxorubicin; Esophageal Neoplasms; Female; Fluorouracil; Gastrointestinal Neoplasms; Humans; Male; Middle Aged; Mitomycin; Mitomycins; Neoplasm Recurrence, Local; Pancreatic Neoplasms; Peplomycin; Stomach Neoplasms; Survival Rate

Chemosensitivity to anticancer drugs was compared between two human esophageal carcinoma cell lines, T.Tn and YES-6 cells. T.Tn cells were more resistant than YES-6 cells to peplomycin (PEP) but not to the other anticancer drugs such as camptothecin, mitomycin C and cytosine arabinoside. Western blot analysis showed higher expression levels of m-calpain and activated mu-calpain in T.Tn cells than in YES-6 cells. On the other hand, YES-6 cells showed a high expression level of calpastatin, which is a calpain-specific endogenous inhibitor. To investigate whether calpain activity was involved in the chemosensitivity, T.Tn cells were transfected with calpastatin cDNA in an inducible expression vector. The induction of calpastatin was accompanied by increased chemosensitivity to PEP. The increases in calpastatin levels were followed by serial increases in the expression levels of NF-kappaB p65 and Fas. Since purified m- or mu-calpain degraded NF-kappaB p65 in vitro, it is possible that calpastatin suppressed calpain-mediated degradation of NF-kappaB p65. Fas ligand (Fas-L) protein levels increased after treatment of the parental T.Tn and calpastatin-transfected cells with PEP, suggesting the synergism between calpastatin-induced Fas and PEP-induced Fas-L. These results suggest that calpain/calpastatin expression levels are effective markers for predicting the sensitivity of human esophageal carcinoma cells to PEP.

Topics: Antibiotics, Antineoplastic; Calcium-Binding Proteins; Carcinoma; Cell Line, Tumor; Esophageal Neoplasms; Fas Ligand Protein; fas Receptor; Humans; Peplomycin; Transcription Factor RelA

A new dosage formulation consisting of an anticancer drug bound to activated carbon particles was developed for the treatment of digestive cancer in patients in whom operation is contraindicated. The new formulation is designed to distribute higher levels of anticancer drug to the regional lymph nodes and at the injection site compared to distribution of the drug in aqueous solution. In 12 patients with histologically proven carcinoma (7 with superficial esophageal cancer and 5 with early or proper muscle layer-infiltrating gastric cancer), an anticancer drug bound to carbon particles (total dose, 40-100 mg peplomycin or 250-500 mg methotrexate per person) was injected endoscopically into the primary lesions. Eleven of the 12 patients are currently alive, 12-64 months after therapy, or they died without evidence of cancer 12-98 months after the treatment. One patient has remained cancer-free for 32 months after a second course of the new formulation therapy given to treat a recurrence detected 26 months after the first treatment. Endoscopic injection of this new dosage formulation seems to control these digestive cancers in patients in whom operation is contraindicated.

Topics: Adenocarcinoma; Adsorption; Aged; Aged, 80 and over; Antineoplastic Agents; Carbon; Carcinoma, Squamous Cell; Esophageal Neoplasms; Female; Humans; Injections, Intralesional; Lymphatic Metastasis; Male; Methotrexate; Middle Aged; Neoplasm Recurrence, Local; Peplomycin; Pilot Projects; Stomach Neoplasms; Survival Rate

We produced two types of murine monoclonal antibodies, KYSM-1 and KIS-1, against human squamous cell carcinoma of the esophagus for quantitative diagnosis and optimum therapy. The isotypes of KYSM-1 and KIS-1 were IgM and IgG1, respectively. Immunohistochemical staining demonstrated that both antibodies strongly reacted with human carcinoma cell lines of the esophagus, lung and oral cavity. Fluorescence activated cell sorter analysis demonstrated that each antigen of KYSM-1 and KIS-1 exposed to cellular membrane of squamous carcinoma cells and molecular weights of these antigens detected by KYSM-1 and KIS-1 were 60 kDa and 90 kDa, respectively, in non-reduced condition. These 2 monoclonal antibodies were labeled with 125I by the Iodogen method, and each antibody was injected into nude mice with human squamous cell carcinoma of the esophagus. Regarding in vivo accumulation of 125I-labeled antibodies, however, KIS-1 alone showed significantly high values in the tumor at 5 and 7 days after the injection. From this result, KIS-1 was labeled with 131I and injected into the tumor-bearing mice with a dose of 200 microCi. Moderately effective results were found in the tumor by 14 days after the injection. Furthermore, KIS-1 was also conjugated to peplomycin (PEP). In in vitro and in vivo effects of targeting chemotherapy, the conjugates killed human squamous carcinoma cells and tumor-implanted nude mice. These results suggest that the 131I-labeled KIS-1 and/or KIS-1-PEP conjugate may provide a targeting therapy in patients with squamous cell carcinoma of the esophagus.

Topics: Animals; Antibodies, Monoclonal; Carcinoma, Squamous Cell; Esophageal Neoplasms; Humans; Immunotoxins; Mice; Mice, Nude; Neoplasm Transplantation; Peplomycin

Activated carbon particle adsorbed-peplomycin (PEP-CH) was administered to three patients who had advanced esophageal cancer and its clinical usefulness was evaluated. The PEP-CH was injected endoscopically into the tumor or the adjacent normal esophageal tissue. Case 1 and case 3 were treated by topical injection of PEP-CH with or without surgery and case 2 was subjected to the PEP-CH treatment with radiation. The barium swallow and endoscopic examination exhibited a marked tumor reduction in all the patients at the end of the PEP-CH treatment. Although a marked clinical response was seen, case 1 died of postoperative complication. Two patients were capable of oral food intake after the treatment, which had been impossible before the treatment. There were no serious adverse side effects caused by the PEP-CH treatment in all the patients. PEP-CH should prove valuable as a new form of chemotherapy for the treatment of esophageal cancer patients.

Topics: Aged; Antibiotics, Antineoplastic; Bleomycin; Carbon; Carcinoma, Squamous Cell; Drug Carriers; Esophageal Neoplasms; Esophagoscopy; Humans; Male; Middle Aged; Peplomycin; Pilot Projects

A new drug-delivery format comprising activated carbon particles adsorbing peplomycin (PEP-CH) was developed for the treatment of superficial esophageal cancer.. The drug distribution was measured in rats that received subcutaneous injections of PEP-CH or peplomycin aqueous solution. In 6 patients with superficial esophageal cancer, peplomycin as PEP-CH, 5-10 mg once a week for 4-10 weeks (total, 40-100 mg/patient) was injected endoscopically into primary lesions.. Rats given PEP-CH had significantly higher peplomycin levels in the regional lymph nodes and the injection site than rats given aqueous solution. Five patients have survived to the present or died without cancer after 27-72 months. The remaining patient has survived without cancer for 8 months after a second course of PEP-CH against recurrence.. PEP-CH therapy seems to have a good therapeutic effect on superficial esophageal cancer, although the present clinical study may have been biased by patient selection.

Topics: Aged; Aged, 80 and over; Animals; Antibiotics, Antineoplastic; Bleomycin; Carcinoma, Squamous Cell; Endoscopy; Esophageal Neoplasms; Female; Follow-Up Studies; Humans; Injections; Lymph Nodes; Male; Middle Aged; Peplomycin; Pilot Projects; Rats; Rats, Inbred Strains; Tissue Distribution

Sixteen inoperable esophageal cancer patients, including six over 80 years of age, were given combined chemoradiation therapy. The treatment consisted of radiation therapy (50-60 Gy for 6-7 wk on days 1 to 46) combined with cisplatin (50 mg/m2 i.v. on days 22 and 50), vindesine (3 mg/m2 i.v. on days 22 and 50) and pepleomycin (5 mg i.m. on days 23 to 27 and 51 to 55). The treatment was well-tolerated. The overall response rate was 56%, with three complete responses and six partial responses. For 10 patients with loco-regional disease (stage II-III), the response rate was 70%. The overall median survival was 7 mo and the survival rate was 31% at one year and 23% at two years. For loco-regional disease, the one and two-year survival rates were 40 and 27%, respectively, with a median survival of 8 mo. The protocol is worthy of being considered for treating inoperable, poor-risk esophageal cancer patients.

Topics: Actuarial Analysis; Aged; Aged, 80 and over; Antibiotics, Antineoplastic; Antineoplastic Combined Chemotherapy Protocols; Bleomycin; Cisplatin; Combined Modality Therapy; Esophageal Neoplasms; Female; Humans; Male; Middle Aged; Peplomycin; Radiotherapy Dosage; Survival Analysis; Treatment Outcome; Vindesine

We have developed a new dosage form, PEP-CH, consisting of peplomycin adsorbed onto small activated carbon particles. Ten patients with inoperable advanced esophageal cancer were treated with endoscopic local injection of PEP-CH combined with radiation using 60Co. Two of 5 patients who completed the treatment have survived over one year (19 and 23 months) now.

Topics: Aged; Antibiotics, Antineoplastic; Bleomycin; Carbon; Cobalt Radioisotopes; Combined Modality Therapy; Delayed-Action Preparations; Esophageal Neoplasms; Humans; Male; Middle Aged; Peplomycin; Prognosis

We attempted intra-arterial infusion chemotherapy using a reservoir system in recurrent cervical lymph nodes after surgery for esophageal cancer, and obtained favorable results. Intra-arterial infusion chemotherapy (75 mg of cisplatin and 5 mg of peplomycin) was performed using a reservoir system connected with a catheter inserted into the left subclavian artery, because recurrent lymph nodes developed in the left supraclavicular fossa. The therapy was effective for 6 months and the quality of life was improved without side effects.

Topics: Antineoplastic Combined Chemotherapy Protocols; Bleomycin; Carcinoma, Squamous Cell; Cisplatin; Drug Administration Schedule; Esophageal Neoplasms; Fluorouracil; Humans; Infusion Pumps, Implantable; Infusions, Intra-Arterial; Lymph Nodes; Lymphatic Metastasis; Male; Middle Aged; Neck; Peplomycin; Picibanil; Postoperative Period

The efficiency of the subrenal capsule assay (SRCA) was studied with fresh tissue of esophageal squamous cell carcinoma. The day-to-day changes in 10 carcinoma cases were evaluated for 9 days. The cancer cells continued to proliferate from the 3rd to the 7th day after the implantation and then decreased. The host reaction was recognized histologically from the 3rd or 4th day to the 9th day. However, the immune reaction did not significantly influence the evaluation of SRCA until the 7th day. The immunohistochemical staining with anti-bromodeoxyuridine monoclonal antibody revealed the existence of cancer cells at the DNA synthesizing stage (S stage) in the graft until the 7th day. In chemosensitivity test by SRCA, 21 patients were studied, and all were evaluable. 5-FU administration produced a response in 8/21 cases (38.1%), VDS in 8/21 (38.1%), and CDDP in 3/21 (14.3%). Used in combination, CDDP + VDS was effective in 7/18 cases (38.9%) and CDDP + BLM in 6/18 cases (33.3%).

Topics: Aged; Animals; Antineoplastic Combined Chemotherapy Protocols; Bleomycin; Carcinoma, Squamous Cell; Cell Division; Esophageal Neoplasms; Female; Fluorouracil; Humans; Immunohistochemistry; Mice; Middle Aged; Neoplasm Transplantation; Organoplatinum Compounds; Peplomycin; Subrenal Capsule Assay; Time Factors; Vindesine

We experienced a long-term survived case with unresectable Stage 4 esophageal carcinoma well responded to chemoradiotherapy of combination of cisplatin (C), vindesine (V) and peplomycin (P) with radiotherapy (R). The patient was a male, aged 53, and diagnosed to have carcinoma, 8 cm in length, located at the IuCe region of the esophagus and right subclavicular lymph node metastasis on admission. He received radiotherapy at total dose of 60 Gy for the primary and metastatic lesions, and also 2 cycle CVP chemotherapy concomitantly. The mass of the primary lesion endoscopically changed to a flat area with small erosion while the right subclavicular metastatic node disappeared and was not found on CT after the end of the treatment. Objective response of this case was determined to the partial response since carcinoma cells were still found at the flat lesion. After discharge, 9 cycles of CVP therapy were further given in 3-year periods. At present, the patient is alive well although a part of the primary esophageal lesion is proved to have malignancy on biopsy.

Topics: Antineoplastic Combined Chemotherapy Protocols; Bleomycin; Cisplatin; Combined Modality Therapy; Esophageal Neoplasms; Humans; Male; Middle Aged; Neoplasm Staging; Peplomycin; Remission Induction; Vindesine

Topics: Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Bleomycin; Carcinoma, Squamous Cell; Cisplatin; Combined Modality Therapy; Doxorubicin; Drug Evaluation; Esophageal Neoplasms; Female; Humans; Male; Middle Aged; Peplomycin

Topics: Antineoplastic Combined Chemotherapy Protocols; Bleomycin; Cisplatin; Combined Modality Therapy; Esophageal Neoplasms; Humans; Male; Middle Aged; Mitomycin; Mitomycins; Peplomycin; Radiotherapy Dosage; Radiotherapy, High-Energy

Topics: Aged; Aged, 80 and over; Antineoplastic Combined Chemotherapy Protocols; Bleomycin; Cisplatin; Combined Modality Therapy; Esophageal Neoplasms; Female; Humans; Male; Middle Aged; Neoplasm Recurrence, Local; Peplomycin; Radiotherapy Dosage; Vindesine

The antitumor activity of several chemotherapeutic agents against a total of 30 clinical samples obtained from 30 human tumors from the esophagus (12), stomach (10), colorectum (6) and lung (2), were tested by subrenal capsule assay (SRCA) using normal immuno-competent BDF, mice. The antitumor activity was evaluated by changes in both tumor size (delta TS method) and tumor growth inhibition rate (TGIR method). Among the 30 tumors, 15 were also tested by human tumor clonogenic assay (HTCA) and the results obtained in the two assays were compared. In the SRCA, adequate growth of the tumor in the control group for evaluation of the response of the treated group was obtained from 27 out of 30 tumors (90%). With activity criteria set at delta TS less than or equal to -1.0 dmm and TGIR greater than or equal to 50%, 41% of the drugs tested were active in delta TS while 27% were active in TGIR. When relationships between antitumor activities evaluated by delta TS and TGIR was compared, both activities were well correlated (r = -0.64). Correlations between tumor responses in the HTCA and in the SRCA were tested in 6 tumors treated with 20 drugs. The overall accuracy was 60% by the TGIR method and 70% by the delta TS method, respectively.

Topics: Animals; Antineoplastic Agents; Bleomycin; Cisplatin; Colonic Neoplasms; Colony-Forming Units Assay; Doxorubicin; Esophageal Neoplasms; Humans; Mice; Mitomycin; Mitomycins; Peplomycin; Rectal Neoplasms; Stomach Neoplasms; Tumor Stem Cell Assay; Vindesine

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

Combined chemotherapy with cisplatin was performed in patients with advanced esophageal cancer. Two types of administration schedule were used: method I (three-drug combination of cisplatin, bleomycin and methotrexate) and method II (combination of cisplatin, peplomycin and methotrexate). Of 16 cases, 6 (37.5%) showed partial remission. With regard to the method of administration, the response rate for method I was 33%, and that for method II was 43%. Nausea (84%), vomiting (56%), loss of appetite (94%), malaise (75%) and alopecia (25%) were observed as side effects. Nausea and vomiting were ameliorated by use of metoclopramide. In bloodchemistry, anemia (87%), leukopenia (56%), thrombopenia (31%) and increase of BUN (63%) were observed. However, these changes were ameliorated by hydration or blood transfusion. Combined chemotherapy with CDDP should be a more useful future treatment for esophageal cancer.

Topics: Aged; Antineoplastic Combined Chemotherapy Protocols; Bleomycin; Cisplatin; Drug Administration Schedule; Esophageal Neoplasms; Female; Humans; Male; Methotrexate; Middle Aged; Peplomycin

Hyperthermo-chemo-radiotherapy (HCR) was prescribed for a patient with superficially spreading esophageal cancer, since severe lung dysfunction presented too great a surgical risk. Viable cancer cells completely disappeared after HCR and 8 months later, at this writing, the patient is living in good condition. Conservative treatment with HCR for patients with esophageal cancer is effective for carefully selected patients.

Topics: Aged; Bleomycin; Carcinoma, Squamous Cell; Cobalt Radioisotopes; Combined Modality Therapy; Esophageal Neoplasms; Humans; Hyperthermia, Induced; Male; Peplomycin; Radioisotope Teletherapy

Sixteen patients with advanced or recurrent squamous cell carcinoma of the esophagus were treated with cisplatin 80 mg/m2 i.v. on day 1, methotrexate 40 mg/m2 i.v. on day 2 and peplomycin 15 mg/day 24 hours continuous subcutaneous infusion from day 2 to day 5. Each course was repeated every 3 weeks. The overall response rate was 56% (9/16) with no complete response. Of 10 patients with no prior therapy, 7 (70%) showed partial response. Toxic effects were acceptable with no fatalities, but severe nausea and vomiting (56%), transient nephrotoxicity (44%), anemia (44%), thrombocytopenia (31%) and leukocytopenia (19%) occurred. No clinical evidence of pulmonary toxicity was seen. The dose-limiting toxic effect of this regimen was myelosuppression.

Topics: Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Bleomycin; Cisplatin; Drug Administration Schedule; Esophageal Neoplasms; Female; Humans; Male; Methotrexate; Middle Aged; Neoplasm Recurrence, Local; Peplomycin

Combination chemotherapy with cis-diamminedichloroplatinum (CDDP) and other anticancer agents was performed in patients with advanced esophageal cancer. From July 1982 to September 1984, 16 patients were entered into this study and divided into two regimens. In regimen I, 5 patients were treated with a daily dose of 20 mg CDDP and 10 mg Peplomycin for five consecutive days and 10 mg Mitomycin C on the first day. This course was repeated 2 or 3 times every 4 weeks. As for evaluation, 1 PR (20%) and 4 NC (80%) were observed. In regimen II, nine patients were treated with daily doses of 25 mg CDDP and 2 mg Vindesine for 5 consecutive days, a course which was repeated every 4 weeks. As for evaluation, 1 CR (9%), 1 PR (9%), 4 MR (36%), 2NC (18%), and 3 PD (27%) were observed. Major side effects were renal failure, bone marrow suppression, nausea and vomiting, which were mostly transient. However, more severe bone marrow suppression was observed in regimen I composed with regimen II.

Topics: Adult; Aged; Anorexia; Antineoplastic Combined Chemotherapy Protocols; Bleomycin; Bone Marrow; Cisplatin; Drug Administration Schedule; Esophageal Neoplasms; Female; Humans; Male; Middle Aged; Mitomycin; Mitomycins; Nausea; Peplomycin; Vinblastine; Vindesine; Vomiting

Neo-adjuvant chemotherapy, followed by definitive surgery and/or radiotherapy was utilized in nine patients with carcinoma of the hypopharynx and cervical esophagus starting in December, 1983. They were treated with combination chemotherapies which included CDDP, PEP (BLM), and MTX. The patients' ages ranged from 52 to 70 years with an average of 57. The histologic types were all squamous cell carcinoma and performance status was 1 in all cases. There were 7 stage III and 2 stage IV. Of 9 patients, 3 showed complete response and 6 showed partial response of the primary tumor with an overall response rate of 100%. Of 8 patients, 3 showed complete response and 2 showed partial response of the metastatic node with an overall response rate of 62.5%. Toxic effects included alopecia in 9 patients, nausea/vomiting in 7, eczema in 4, RBC below 350 X 10(4)/mm3 in 5, WBC below 3000/mm3 in 1, peak serum creatinine above 2 mg/dl in 1. All patients except one with renal toxicity were able to start definitive treatment soon after chemotherapy, the primary and regional lesions being subsequently well controlled in all 9 patients. Neo-adjuvant chemotherapy appears to be very effective for the reduction of tumor bulk. This multidisciplinary therapy should be expected to increase survival rate.

Topics: Aged; Antineoplastic Combined Chemotherapy Protocols; Bleomycin; Carcinoma, Squamous Cell; Cisplatin; Drug Administration Schedule; Esophageal Neoplasms; Female; Humans; Hypopharyngeal Neoplasms; Lymphatic Metastasis; Male; Methotrexate; Middle Aged; Peplomycin; Pharyngeal Neoplasms

Topics: Bleomycin; Esophageal Neoplasms; Humans; Male; Middle Aged; Ointments; Peplomycin

Between January 1970 and December 1983, 148 patients of esophageal carcinoma were treated surgically in the 2nd Department of Surgery, Osaka University Medical School. Among these patients, 70 (48.6%) with suspected invasion to neighboring structures were treated with preoperative chemotherapy, radiotherapy or a combination of both. The chemotherapeutic agents used were tegafur (FT-207)-suppository, bleomycin (BLM) or peplomycin (PEP). Radiotherapy (3000-4000 cGy) for selected cases was begun at the same time as the chemotherapy. Three to four weeks after the chemotherapy and radiotherapy were completed, esophagectomy was performed. The effects of the preoperative adjuvant therapies were investigated in these patients, and the following results were obtained: A marked histological effect, according to the Guide Lines in Clinical and Pathologic Studies for Carcinoma of the Esophagus (Japanese Society for Esophageal Diseases, 1976) was found in 47.4% of the radiotherapy plus FT-207 group, 39.1% of the group receiving radiotherapy alone and 28.6% of the group receiving radiotherapy plus PEP or BLM. Radiotherapy plus FT-207 showed excellent effects (77.8% of this group showed marked histological effects) on well differentiated squamous cell carcinoma, as shown histologically by biopsy specimens. Tumors exhibiting sharp edged margins radiographically and endoscopically, showed a very good histological effect after preoperative radiotherapy. Metastatic lymph nodes present in the irradiation field, whose primary lesion showed a marked histological effect, also gave excellent results. Postoperative radiotherapy is also expected to be equally effective on these cases.

Topics: Antineoplastic Combined Chemotherapy Protocols; Bleomycin; Combined Modality Therapy; Esophageal Neoplasms; Humans; Peplomycin; Preoperative Care; Prognosis; Radiotherapy Dosage; Suppositories; Tegafur

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

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

We studied treatment methods after fistula formation in 14 esophageal carcinoma patients with broncho-esophageal fistulae. Among 12 patients, 8 had no treatment, one was operated and 3 underwent radiotherapy using conventional fractionation. In only one case was there temporary closure of the fistula; none of the patients survived for more than 1 year. The other 2 patients were treated by the long protracted method (1.5 Gy/day). Long-term closure of the fistula was seen. These patients received additional low-dose rate teletherapy (1 Gy/hour, 7 Gy/day) and both survived for over 1 year.

Topics: Aged; Bleomycin; Bronchial Fistula; Combined Modality Therapy; Esophageal Fistula; Esophageal Neoplasms; Female; Humans; Male; Middle Aged; Peplomycin; Radiography; Radiotherapy Dosage; Radiotherapy, High-Energy

Pepleomycin ointment was developed to improve the antitumor activity afforded by endoscopic therapy for esophageal cancer. Through the esophagoscope we could observe this ointment specifically attacking the lesion. Furthermore we were able to recognize that peplomycin was acting directly on the lymph nodes as well as the tumor in a resected portion of the esophagus. It is hopefully anticipated that this method will be used as a combination therapy in pre-operative and inoperable esophageal cancer.

Topics: Aged; Antibiotics, Antineoplastic; Bleomycin; Esophageal Neoplasms; Esophagoscopy; Humans; Male; Middle Aged; Ointments; Peplomycin

Eight esophageal squamous cell cancer patients were treated with local hyperthermochemotherapy plus ethanol in addition to bypass surgery and supraclavicular esophagostomy. Local hyperthermochemotherapy plus ethanol treatment was as follows: The esophagus was perfused for one hour using esophagostomy with warmed saline (42-44 degrees C) containing 6-10% ethanol, the overflowing saline was aspirated. Simultaneously, 15 mg Bleomycin or 10 mg Peplomycin was administered intravenously and 5 mg Bleomycin or Peplomycin was administered directly to the esophageal site. This procedure was repeated twice a week for a total of 10 to 24 times. Six of the 8 patients (75%) thus treated showed a shortening of the duration of the shadow defect in X-radiograms. In one case, the lesion was removed and the patient is doing well 9 months after the operation.

Topics: Aged; Antibiotics, Antineoplastic; Bleomycin; Carcinoma, Squamous Cell; Esophageal Neoplasms; Esophagoplasty; Ethanol; Female; Hot Temperature; Humans; Male; Methods; Middle Aged; Peplomycin

For the purpose of verifying the effectiveness of peplomycin, one of the derivatives of bleomycin, against carcinoma of the esophagus and the safety of it, the analysis of the data for total 113 cases collected from 25 institutions in Japan was made. The results are as follows. It was effective in 19 out of 74 evaluable cases of carcinoma of the esophagus (25.7%). In case of treatment with peplomycin alone, it was effective in 6 out of 39 cases (15.4%). In case of the combination treatment with peplomycin and some other therapy, it was effective in 13 out of 35 cases (37.1%). As for the side effects, the incidence of fever was the highest in both the cases of peplomycin alone and the combination treatment such as 39.6% and 37.0%, respectively. Anorexia, nausea, vomiting, respiratory symptoms and tiredness were found in relatively many cases. In the clinical laboratory tests, the vital capacity after the treatment tended to be lower than that before the treatment, but there was little change in the hematological tests, pulmonary function test and renal function test.

Topics: Adult; Aged; Antibiotics, Antineoplastic; Bleomycin; Drug Evaluation; Drug Therapy, Combination; Esophageal Neoplasms; Female; Humans; Male; Middle Aged; Peplomycin

A preliminary use of Peplomycin (PEP) was investigated in 14 patients with advanced esophageal cancer. PEP was given intermittently with a dose of 10 mg intravenously twice a week. As side effects there were observed fever elevation in 8 cases, stomatitis in 4 cases, erosion of the skin of the scrotum in 1 case and pigmentation in 1 case, respectively. Dyspnea associated with decrease of PaO2 was observed in 4 cases, which recovered promptly after discontinuing of the administration. Out of 10 evaluable cases, partial response was observed in 1, minor response in 1, no change in 3 and progressive disease in 5 cases, respectively. While the effect was only limited in these experiences, the local injection of PEP into or around the tumor using the external fistula of the remaining esophagus which was made at the time of by-pass operation was discussed.

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

A combined therapy of pepleomycin (NK-613) and radiation was performed in 15 cases of esophageal and cancer. Twelve cases out of 15 were inoperable, and 3 cases were operable. NK-631 was administered by drip intravenous injection at a dose of 5 mg per day for 3 consecutive days weekly, aiming at total dose of 60-120 mg. Tumor regression rates, which were measured by planimeter on esophagogram, were 42-92% (mean 72%): two cases were more than 90%, and more than 50% in 12 cases. An average of the survival period of 15 cases was 57 weeks with 7 cases (46.7%) of 1 year survival, 2 cases (13.3%) of 2 year survival. The side effects of NK-631 observed in the present study consisted of fever 6, stomatitis 2, skin rash 2, and reversible pneumonitis 2. This study suggests that NK-631 exhibit remarkable anti-tumor effects on esophageal carcinoma, and seem to be less toxic.

Topics: Aged; Antibiotics, Antineoplastic; Bleomycin; Carcinoma, Squamous Cell; Esophageal Neoplasms; Female; Humans; Male; Middle Aged; Peplomycin; Radiotherapy Dosage

Topics: Adenocarcinoma; Aged; Animals; Bleomycin; Carcinoma, Squamous Cell; Cells, Cultured; Dogs; Drug Evaluation, Preclinical; Esophageal Neoplasms; Female; Humans; Male; Middle Aged; Peplomycin; Rats

Topics: Aged; Animals; Antibiotics, Antineoplastic; Bleomycin; Carcinoma, Squamous Cell; Cells, Cultured; Dogs; Esophageal Neoplasms; Female; Humans; Male; Middle Aged; Peplomycin; Rats