pirarubicin and Stomach-Neoplasms

The safety of chemotherapy combining TS-1 and pirarubicin (THP) for treatment of recurrent or locally advanced gastric cancer was evaluated. THP was administered by intravenous drip infusion at a dose of 14 mg/m2 every other week. TS-1 was administered orally at a dose of 40 mg/m2 twice a day for 2 weeks followed by 2 weeks of rest (level 1), for 3 weeks followed by 2 weeks of rest (level 2), and for 4 weeks followed by 2 weeks of rest (level 3). Three patients were treated with the level 1 schedule. One patient with peritoneal dissemination received 22 courses of the treatment, and benefited from a long-term NC. However the remaining 2 cases were diagnosed as PD after 4 courses and were withdrawn from further treatment. Two patients in this group suffered from grade 2 adverse events according to the NCI-CTC. Only 1 patient who had liver metastasis was treated at level 2. Fourteen courses were administered, and a PR was achieved while grade 2 adverse events were observed. One of 3 patients who were treated with level 3 had grade 3 adverse events. Consequently, 3 more cases were added to this dose level, and no additional grade 3 adverse events were observed, while grade 2 adverse events were seen in 4 cases. Urinary urgency had completely disappeared in 1 patient with peritoneal recurrence. Myelosuppression, which was the main observed adverse event, was well controlled and of brief duration. The response, including alleviation of clinical symptoms, was confirmed in 3 of 5 chemo-naive patients.

Topics: Adult; Aged; Anemia; Antineoplastic Combined Chemotherapy Protocols; Doxorubicin; Drug Administration Schedule; Drug Combinations; Female; Humans; Leukopenia; Liver; Male; Middle Aged; Nausea; Neoplasm Recurrence, Local; Oxonic Acid; Pyridines; Stomach Neoplasms; Tegafur; Vomiting, Anticipatory

A randomized controlled trial was designed to investigate the therapeutic benefit of a combination chemotherapy consisting of MTX, 5-FU and THP in patients with advanced or recurrent gastric carcinoma. The patients were randomized into two groups; Group A patients (n = 37) underwent our combined chemotherapy, whereas Group B (n = 34) underwent chemotherapy with 5-FU alone as a control. There were no significant differences in various background factors between the groups. The median survival time was roughly 170 days after the randomization for the patients with advanced cancer (n = 26 for Group A and n = 25 for Group B), with no significant difference between the groups. Two long survivors, however, belonged to Group A. The median survival time of 161 days for Group A (n = 11) was longer than that of Group B (84 days, n = 9), but the difference was not statistically significant. The incidence of toxicities (leukopenia in particular) exceeding JCOG grade 3 was significantly higher for Group A, but no morbidity was observed. These results imply that patients with advanced or recurrent gastric carcinoma may benefit from a regimen of MTX, 5-FU and THP.

Topics: Aged; Aged, 80 and over; Antimetabolites, Antineoplastic; Antineoplastic Combined Chemotherapy Protocols; Doxorubicin; Drug Administration Schedule; Female; Fluorouracil; Humans; Male; Methotrexate; Middle Aged; Neoplasm Recurrence, Local; Stomach Neoplasms; Survival Analysis

To investigate the effect on gastric cancer and metastatic lymph node, an emulsion made of pirarubicin and lipiodol mixture was injected around the lesion of the gastric cancer using gastrointestinal endoscopy. At the site of emulsion injection and lymph node, the concentration of the THP Lipiodol emulsion was enough despite injection more than 7 days before. This targeting therapy for metastatic lymph nodes was considered effective.

Topics: Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Doxorubicin; Emulsions; Female; Gastroscopy; Humans; Injections, Intralesional; Iodized Oil; Lymph Nodes; Lymphatic Metastasis; Male; Middle Aged; Stomach Neoplasms

Topics: Aged; Antineoplastic Combined Chemotherapy Protocols; Doxorubicin; Drug Administration Schedule; Female; Fluorouracil; Humans; Male; Methotrexate; Middle Aged; Neoplasm Recurrence, Local; Pilot Projects; Stomach Neoplasms

Nineteen patients diagnosed with peritoneal carcinomatosis were treated by in-home chemotherapy over a period of four years from August, 1990 to July, 1994. Primary diagnoses of the four male and 15 female patients included 12 cases gastric cancer (four males, eight females), five cases of ovarian cancer, one case (female) of appendicular cancer, and one case (female) of breast cancer. In addition to oral administration of UFT-E and 5'-DFUR, chemotherapy included weekly intravenous injection of a massive dose of 5-FU (1,000 mg/m2), subselective intraaortic infusion and intraperitoneal infusion using a reservoir. These methods were used individually and in combination. The drugs used included 5-FU, CBDCA, CPA, THP, and EPIR. Subselective intraaortic infusion was performed by low dose continuous infusion using the Baxter infusor multiday type. Six gastric cancer patients lived normally for over one year, while four died in less than a year. All ovarian and appendicular cancer patients were CR, the breast cancer patient was PR. Ten patients continued working at their jobs while receiving at home chemotherapy treatments. Diuretics were used to alleviats ascites. Although there were no side effects on digestive organs, 5-FU and CBDCA were mixed with 100 mg hydrocortisone in the infusor to improve cachexia, and promote appetite and activity. Bone marrow suppression was very slight at these dosages, and weekly checkups were adequate. The at-home rate (number of days at home/entire period since onset) of all patients was 78%.

Topics: Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Carboplatin; Cyclophosphamide; Doxorubicin; Drug Administration Schedule; Epirubicin; Female; Fluorouracil; Home Care Services, Hospital-Based; Home Infusion Therapy; Humans; Infusion Pumps, Implantable; Infusions, Parenteral; Male; Middle Aged; Ovarian Neoplasms; Peritoneal Neoplasms; Stomach Neoplasms

A multi-institutional collaborative phase II study of (2"R)-4-O-tetrahydropyranyladriamycin (THP) was performed by intravenous administration to patients with advanced or recurrent gastric cancer. The administration schedules were (1) 40-60 mg/body every 3 or 4 weeks and (2) 20-40 mg/body once a week. Of 58 registered patients, 49 cases were eligible and 37 cases were evaluable for response. The therapeutic results were 1 CR, 4 PR, 14 NC and 18 PD. The response rate of the evaluable cases was 13.5%. The side effects were mainly bone marrow suppression and digestive symptoms. In particular, the frequency of leukopenia was a high 75.5%, while there was a decrease in hemoglobin in 38.8% and anorexia in 30.6%. The frequency and severity of alopecia, which is a known problem with anthracyclines, were slight, and no abnormal electrocardiograms were observed.

Topics: Adenocarcinoma; Adult; Aged; Anorexia; Bone Marrow; Doxorubicin; Drug Administration Schedule; Female; Humans; Infusions, Intravenous; Leukopenia; Male; Middle Aged; Stomach Neoplasms

The history of adjuvant chemotherapy for gastric cancer in Japan was overviewed. As the most important trials of the early days, the trials of Imanaga Group (Cooperative Study Group supported by the grants from the Ministry of Health and Welfare) and of National Cancer Center Hospital were presented with final results. Furthermore, as the recent trials, the results of Cooperative Study Group of Surgical Adjuvant Chemotherapy for Gastric Cancer in Japan (organized by Prof. K. Inokuchi) and of our study at Hiroshima University Hospital were presented. More than ten years has passed since the above early trials took place and the increase of five-year survival rate was clearly demonstrated in comparing the results obtained earlier days and current ones especially in stage III cases. This increase is attributed to the advances of cancer chemotherapy in the province of surgery.

Topics: Antibiotics, Antineoplastic; Clinical Trials as Topic; Doxorubicin; Drug Therapy, Combination; Humans; Mitomycin; Mitomycins; Stomach Neoplasms; Suppositories; Tablets; Tegafur

Little evidence is known from experimental research for intraoperative hyperthermic intraperitoneal chemotherapy. This study was to investigate the effect of hyperthermic chemotherapy on gastrointestinal cancer cells in vitro and explore the possible factors which may affect this method.. Gastric cancer cell line MGC-803 and intestinal cancer cell line HCT-116 were chosen. Cells were treated with different drugs, temperatures and duration. Cell viability and growth were measured by MTS-PMS assay. The morphology of the cells was observed under a microscope.. Significant synergistic effect was observed when the two cancer cell lines were treated with 5-FU, MMC, DDP and THP in combination with elevated hyperthermia from 41 degrees C to 45 degrees C compared with control group (P<0.01). The strongest effect was achieved at 45 degrees C, which the inhibitory effects of these four drugs were 61.7%, 79.2%, 88.7%, 94.7% on MGC-803 and 76.4%, 78.7%, 77.8%, 91.7 on HCT-1116, respectively. The inhibitory effect demonstrated a time and dose-dependent manner in HCT-116 cells within a certain period of time. The effect revealed a flat curve after 90 min when HCT-116 was treated with 43 centigrade. THP had the strongest effect at any conditions among all tested drugs (P<0.01). Either simple thermotherapy or chemohyperthermia displayed considerable killing effects on cancer cells which were confirmed by microscope observation. And a great deal of dead cells were observed when treated with chemohyperthermia.. DDP or MMC reveals relatively satisfactory antitumor effects with the optimal temperature of 43-45 degrees C. Taken practical application into consideration, 60 min may be selected in clinical use. Synergistic antitumor effects of THP in combination with hyperthermia were prior to 5-FU, DDP or MMC, which deserve further clinical research.

Topics: Antibiotics, Antineoplastic; Antimetabolites, Antineoplastic; Cell Line, Tumor; Cell Survival; Cisplatin; Colonic Neoplasms; Combined Modality Therapy; Doxorubicin; Fluorouracil; Humans; Hyperthermia, Induced; Mitomycin; Stomach Neoplasms

To evaluate the effect of pirarubicin (THP) in combination with hyperthermia on gastric cancer tissues in vitro and explore the underlying mechanisms.. In vitro three-dimensional culture models were established with tissue biopsies from 36 patients with pathologically confirmed gastric cancer. The tumor cell viability was measured by MTS-PMS assay, and HE staining was used to study the histomorphological changes of the tissues following chemotherapy and hyperthermia.. Synergistic tumor cell-killing effects of cisplatin, THP, and mitomycin with hyperthermia was observed in the tumor tissues (P=0.000), and THP exhibited stronger cytotoxic effects than the other drugs. Histomorphological study suggested strong killing effects of THP on the tumor tissues, which displayed disrupted tissue structure, cellular degradation and necrosis, karyopyknosis and karyolysis, with cytoplasm loss. The anti-tumor effects of THP were associated with clinical staging and pathological grading of the tumors (P=0.000), but not with the patients' gender, age, tumor size and preoperative CEA levels (P>0.05).. Pirarubicin shows good synergistic effects with hyperthermia, and the cytotoxicity of pirarubicin against gastric cancer tissue is enhanced considerably by mild hyperthermia. THP can be a potential therapeutic drug for intraperitoneal chemohyperthermia.

Topics: Adenocarcinoma; Adult; Aged; Aged, 80 and over; Antineoplastic Agents; Cell Survival; Cisplatin; Doxorubicin; Drug Synergism; Female; Hot Temperature; Humans; Hyperthermia, Induced; Male; Middle Aged; Mitomycin; Stomach Neoplasms; Tissue Culture Techniques; Tumor Cells, Cultured

In the treatment of 2 patients with recurrent gastric cancer who showed bone metastasis and lymph node recurrence, we administered 30 mg/body of pirarubicin (THP) on the first day of treatment, and 30 mg/body of cis-platinum (CDDP) and 500 mg/m2 of 5-fluorouracil (5-FU) for 3 days (FP therapy). Marked effects were achieved. Gastric cancer of Borrmann IV type was diagnosed in Case 1, and total gastrectomy was performed. The histological type was poorly differentiated adenocarcinoma, and the histological classification was II. A bone metastasis was found three years after operation. The patient was CR after three courses of treatment, and has survived for 2 years. In Case 2, advanced gastric cancer was treated with neoadjuvant chemotherapy and distal gastrectomy. The histological type was moderately differentiated adenocarcinoma, and the histological classification was IIIa. Obstructive jaundice due to lymph node recurrence developed 6 years after operation. Two courses of treatment were provided after PTCD, and PR was observed. The patient has survived for 3 months. Both patients exhibited mild side effects such as anemia and leukocytopenia, but no serious complications were observed. Although various dosage regimens of FP therapy have been investigated, there has been a certain limit to the response rate achieved by this therapy, and new protocols have been explored. We achieved marked effects in 2 patients by adding THP to FP therapy. These cases are reported here together with some discussion of cases reported in the literature.

Topics: Adenocarcinoma; Aged; Antineoplastic Combined Chemotherapy Protocols; Cisplatin; Combined Modality Therapy; Doxorubicin; Drug Administration Schedule; Female; Fluorouracil; Gastrectomy; Humans; Middle Aged; Stomach Neoplasms

There have been few effective chemotherapeutic regimens for scirrhous type gastric cancer. Recently, the usefulness of combined cancer agent chemotherapy based on the concept of biochemical modulation has been reported. For example sequential MTX and 5-FU therapy, low-dose CDDP plus 5-FU, and the like. In this paper, we report the usefulness of low-dose CDDP plus 5-FU therapy in combination with pirarubicin (THP) for inoperable scirrhous type gastric cancer. A 32-year-old man who was suffering from scirrhous type gastric cancer with pyloric stenosis was treated with this regimen. Eight weeks after the start of therapy, his gastric capacity and lumen diameter had clearly increased, and he was taking ordinary meals. Ascites had also completely disappeared. CR has now been continued about 7 months. This regimen is considered to be promising for scirrhous type gastric cancers with a poor prognosis.

Topics: Adenocarcinoma, Scirrhous; Adult; Antineoplastic Combined Chemotherapy Protocols; Cisplatin; Doxorubicin; Drug Administration Schedule; Fluorouracil; Humans; Infusions, Intravenous; Male; Stomach Neoplasms

We experienced a case of multiple liver metastasis from postoperative gastric cancer who showed long-term survival with hepatic arterial infusion chemotherapy (HAI) of MMC and pirarubicin. A catheter was inserted into the hepatic artery, and 4 mg of MMC and 20 mg of pirarubicin were administered through an implantable port catheter every two to four weeks. The total dose of MMC and pirarubicin by the time of this report was 164 mg and 820 mg, respectively. The follow-up CT scan 2 months after the beginning of HAI showed a decrement of the liver tumors. The decrease rate at 12 and 17 months was 50% and 70%, respectively, which was diagnosed as partial response (PR). The therapeutic effect at 49 months is still PR without any sign of tumor enlargement of extra hepatic lesion.

Topics: Antineoplastic Combined Chemotherapy Protocols; Doxorubicin; Gastrectomy; Hepatic Artery; Humans; Infusion Pumps, Implantable; Infusions, Intra-Arterial; Liver Neoplasms; Male; Middle Aged; Mitomycin; Stomach Neoplasms; Survivors

Although the mechanism of P-glycoprotein (Pgp)-related resistance of doxorubicin is known, it has not been clarified for other anthracycline derivatives. We have examined the chemosensitivity of gastric cancer tissues to three anthracyclines in relation to Pgp expression.. Sixty-six surgical specimens obtained from patients with gastric cancer were subjected to histoculture drug response assay using doxorubicin (DXR), epirubicin (EPI), and 4'-O-tetrahydropyranyldoxorubicin (pirarubicin; THP). The cutoff concentrations used were 15 microg/ml for DXR and EPI and 17 microg/ml for THP.. A 50% or more inhibition index (I.I.) was regarded as sensitive, at which the correlation rates were 95.8% (23/24) and 74.2% (49/66) for DXR-EPI and DXR-THP, respectively. Twenty-six specimens were immunohistochemically stained with monoclonal antibody to Pgp, with a positive rate of 53.8% (14/26). In Pgp-positive specimens, all cases were resistant to DXR and 28.6% (4/14) of cases were sensitive to THP, while the antitumor activity of EPI was essentially identical to that of DXR.. The expression of Pgp might affect resistance to DXR and EPI, although THP may partially impair this resistance, suggesting the clinical usefulness of THP in treatment of DXR-refractory gastric carcinoma.

Topics: Antibiotics, Antineoplastic; Antineoplastic Agents; ATP Binding Cassette Transporter, Subfamily B, Member 1; Doxorubicin; Drug Screening Assays, Antitumor; Epirubicin; Humans; Immunohistochemistry; Stomach Neoplasms; Tumor Cells, Cultured

A 75-year-old male was admitted one year after surgery for advanced gastric cancer. He was diagnosed as having multiple liver metastases with elevated serum CEA level. Combination chemotherapy consisting of THP-ADM, MMC and 5'-DFUR was done in the outpatient clinic. As a result, both multiple metastatic liver tumors and serum CEA level showed a remarkable response.

Topics: Aged; Antineoplastic Combined Chemotherapy Protocols; Carcinoembryonic Antigen; Combined Modality Therapy; Doxorubicin; Floxuridine; Gastrectomy; Humans; Liver Neoplasms; Male; Mitomycin; Remission Induction; Stomach Neoplasms

In the preclinical study of a new combination therapy for gastric cancer, dFTP, consisting of doxifluridine (5'-DFUR), pirarubicin (THP) and cisplatin (DDP) as a modification of conventional FAP regimen (5-fluorouracil+Adriamycin+DDP), we compared antitumor and toxic effects of two sequential treatment schedules, single injection of DDP before or after 4 daily administrations of 5'-DFUR, on 5 strains of human gastric cancer bearing nude mice. Results indicated that both schedules of the dFTP regimen had potent antitumor effects. There was no significant difference between them. On the other hand, in terms of the host toxicity as observed by body weight loss, the post-DDP schedule was significantly less toxic than pre-DDP. These results suggest that dFTP regimen (post-DDP schedule) may be useful for clinical treatment of gastric cancers.

Topics: Adenocarcinoma; Animals; Antineoplastic Combined Chemotherapy Protocols; Body Weight; Cisplatin; Doxorubicin; Drug Administration Schedule; Female; Floxuridine; Humans; Mice; Mice, Nude; Neoplasm Transplantation; Stomach Neoplasms

We reported a patient with advanced gastric cancer and a liver metastasis, who responded remarkably to combination chemotherapy using THP, 5'-DFUR and CDDP. The patient was administered four courses of THP (15 mg/m2/day, on day 1, iv), 5'-DFUR (1400 mg/m2/day, on days 1-4 and 15-18, orally), and CDDP (80 mg/m2/day, on day 5, iv) every 4 weeks. As a result, both the primary and metastatic tumors decreased remarkably in size at more than 19 weeks (PR) and we performed curative total resection of the stomach and partial resection of the liver. Histologically, the effects of chemotherapy on gastric focus were evaluated as grade 1a and the liver metastasis completely disappeared. This combination therapy proved useful to treat advanced gastric cancer in this patient.

Topics: Adenocarcinoma; Aged; Antineoplastic Combined Chemotherapy Protocols; Cisplatin; Doxorubicin; Drug Administration Schedule; Floxuridine; Gastrectomy; Humans; Liver Neoplasms; Male; Stomach Neoplasms

A 67-year-old man with advanced gastric cancer with multiple liver metastases was treated by a new combination chemotherapy using 5-FU, THP and MMC (FTM). After the first course of FTM, both abnormal liver function and the elevated level of serum CA 19-9 were restored. After the second course of FTM, the primary lesion became a small ulcer around cardia. A partial response was recognized both in the primary lesion and in the liver metastases. No serious side effect was observed except for leukocytopenia, which was controlled by G-CSFS. This new combination chemotherapy (FTM) was suggested to be useful even for far advanced gastric cancer.

Topics: Adenocarcinoma; Aged; Antineoplastic Combined Chemotherapy Protocols; Doxorubicin; Drug Administration Schedule; Fluorouracil; Humans; Liver Neoplasms; Male; Mitomycin; Stomach Neoplasms

Pirarubicin, a new antineoplastic antibiotic of anthracycline derivative, was injected into the pleural cavity in 15 patients with malignant pleural effusion. The dose of pirarubicin was 40 mg or 80 mg/body. All 15 patients were evaluable for both efficacy and toxicity. Since one evaluable patient received two courses of intrapleural administration of pirarubicin, we evaluated a total of 16 courses. Overall response rate was 81.3% with 7 CR cases, 6 PR cases and 3 NR cases. As toxicities, transient elevation of fever was observed in 81.3%, chest pain in 37.5%, appetite loss in 18.8%, nausea in 12.5% and bone marrow suppression in 6.3% of 16 courses, but no alopecia was observed. Between 40 mg group (n = 8) and 80 mg group (n = 8), no significant difference was observed in response rate, response duration, survival duration or toxicities except for fever. Fever over 38 degrees C was observed in all (100%) the 80 mg group, which was significantly higher than 50% in the 40 mg group. Response duration in cases with fever over 38 degrees C (n = 12) was significantly longer than in cases with maximum fever under 38 degrees C (n = 4). Intrapleural administration of pirarubicin was considered to be effective for the treatment of malignant pleural effusion without severe toxicities.

Topics: Adenocarcinoma; Adult; Aged; Anorexia; Carcinoma, Small Cell; Chest Pain; Doxorubicin; Female; Fever; Humans; Infusions, Parenteral; Lung Neoplasms; Middle Aged; Pleural Effusion, Malignant; Stomach Neoplasms; Survival Rate

In vitro MTT assay was applied for examining chemosensitivity with 104 samples; 56 primary tumors, 31 lymph node, 9 liver, and 8 peritoneal metastases, obtained from 87 patients with advanced gastric carcinoma. The rate of effectiveness of various anticancer drugs were as follows; etoposide, 87.7%; cisplatin, 55.1%; mitomycin C, 51.5%; pirarubicin, 50.0%; aclarubicin, 48.8%; carboquone, 31.8%; doxorubicin, 20.3%; and 5-fluorouracil, 12.9%. Etoposide was found to be most effective against gastric carcinoma in this test. Concerning with the metastatic lesions, liver metastases were resistant to all tested drugs. On the other hand, peritoneal metastases were sensitive to etoposide, mitomycin C, and pirarubicin. The results indicate heterogeneity of the chemosensitivity between primary and metastatic lesions, and it was supposed that etoposide might be useful against human gastric cancer.

Topics: Antineoplastic Agents; Carbazilquinone; Cisplatin; Doxorubicin; Drug Screening Assays, Antitumor; Etoposide; Fluorouracil; Humans; Mitomycin; Mitomycins; Stomach Neoplasms; Tetrazolium Salts; Thiazoles; Tumor Cells, Cultured

This report describes a 55-year-old man who had a curative operation for leiomyosarcoma of the stomach 6 years ago. Unresectable liver metastases was discovered during the second laparotomy and successfully treated by intra hepato-arterial chemotherapy, which included MMC, ADM and Therarubicin with Infuse-A-Port. He remains well presently with a decrease in the size of the liver metastases and no metastasis to any other organs upon investigation by an abdominal CT 2 years and 2 months after the second laparotomy.

Topics: Antineoplastic Combined Chemotherapy Protocols; Doxorubicin; Fluorouracil; Hepatic Artery; Humans; Infusion Pumps, Implantable; Infusions, Intra-Arterial; Leiomyosarcoma; Liver Neoplasms; Male; Middle Aged; Mitomycin; Mitomycins; Picibanil; Stomach Neoplasms

In order to deliver a high concentration of anti-cancer drugs in tumor tissue, preoperative intra-arterial injection therapy using Etoposide (VP-16), Pirarubicin (THP-ADM) and Cisplatin (CDDP), was used for 22 patients with resectable advanced gastric cancer. The concentration of VP-16, Adriamycin (ADM) and platinum (Pt) were measured in cancer tissue, normal mucosa and lymphnodes without metastasis at the greater curvature, which were gathered operatively and in serum just before operation. Student's t test was performed with their data. The mean concentration of VP-16 was less than the detectable limit in all tissues and in serum. The mean concentration of ADM in cancer tissue was significantly higher than in normal gastric mucosa, in lymphnodes without metastasis, and in serum. The mean concentration of platinum in cancer tissue was higher than those in lymphnodes, normal mucosa, and serum, but no significant differences were noted among them. It was concluded that the intra-arterial injection of THP-ADM and CDDP was an effective method to maintain a high concentration of ADM and Pt in gastric cancer tissue. However, intra-arterial injection of VP-16 was not useful.

Topics: Antineoplastic Combined Chemotherapy Protocols; Cisplatin; Doxorubicin; Etoposide; Female; Gastric Mucosa; Humans; Injections, Intra-Arterial; Male; Middle Aged; Preoperative Care; Stomach Neoplasms

Fifteen patients with peritoneal metastasis of gastric cancer were treated with mainly ip-ETP (Etoposide: i.p., THP-ADM: i.v. and CDDP: i.p.) or other drugs by the use of a totally implantable peritoneal access system. In principle, intraperitoneal drug delivery was carried out every two weeks. CDDP was administered into the intraperitoneal cavity with intravenous sodium thiosulfate delivered simultaneously to protect against cisplatin-induced nephrotoxicity. RI-scintigram showed that the intraperitoneal catheter was fully useful even six months after the operation. As a result, performance status has been improved in 12 out of 15 cases, and ascites disappeared in 3 out of 6 cases with same. Ten cases have been alive for more than 6 months after operation. There have been no severe complications (e.g., nephrotoxicity or myelosuppression) even in the cases treated at frequent intervals for more than 8 months. The findings in this study indicated that ip-ETP using totally implantable peritoneal access system is beneficial for advanced gastric cancer with peritoneal metastasis.

Topics: Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Cisplatin; Doxorubicin; Drug Evaluation; Etoposide; Female; Humans; Infusion Pumps; Infusions, Parenteral; Male; Middle Aged; Peritoneal Cavity; Peritoneal Neoplasms; Stomach Neoplasms

THP-ADM is a new antitumor agent which belongs to the anthracycline family. This agent has shown a high therapeutic index compared with the mother compound, Adriamycin, in preclinical and clinical studies. This time, a pharmacokinetic study of THP-ADM was performed and the following characteristics of this agent were clarified. A short t 1/2 alpha was noted in comparison with that of Adriamycin in a 3-compartment open model. Leukocyte concentration with THP-ADM was much higher than that of plasma of red blood cells. Renal excretion over 48 hours was 9% and biliary excretion over the same period was 20%. High THP-ADM and low Adriamycin tissue concentrations were revealed in all tissues excluding the liver. In liver tissue, a high concentration of Adriamycin and a low concentration of THP-ADM was observed. A small amount of Adriamycin was noted in the plasma following THP-ADM administration. This was probably related to the small amount of existing Adriamycin in THP-ADM or conversion of THP-ADM to Adriamycin in the liver tissue, or both. Poor penetration of THP-ADM into the third space was noted.

Topics: Doxorubicin; Erythrocytes; Humans; Infusions, Intravenous; Kinetics; Lymph Nodes; Pancreatic Neoplasms; Pleural Effusion; Stomach Neoplasms

To evaluate the therapeutic effects of THP-adriamycin (THP), single agent chemotherapy and combination chemotherapy with THP were undertaken in 16 patients with advanced gastric cancer. In the eight patients in the THP single agent group. Only three minor responses (MRs) were obtained. However, three partial remissions (PRs) and one MR were observed in the eight patients in the THP combination group. In which 5-FU was two patient FT-207 in another two and CDDP in one. No severe side effects were observed with the THP chemotherapy, while leukopenia of less than 3,000/mm was commonly seen (69%). Only three patients showed alopecia. Thrombocytopenia of less than 30,000/mm3 and transient arrhythmia were observed in one patient each. These side effects were apparently milder than those with adriamycin. From a pharmacokinetic study of THP and adriamycin. It was found that THP was superior to adriamycin in its transferability from the blood to cancer tissue. In conclusion, it is suggested that combination chemotherapy with THP is useful for advanced gastric cancer.

Topics: Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Doxorubicin; Female; Fluorouracil; Humans; Male; Middle Aged; Stomach Neoplasms; Tegafur; Uracil

Two patients with recurrent gastrointestinal carcinoma were treated with THP. Partial response was recognized in the local recurrent tumor of one patient and in liver metastasis of a second patient. THP was administered every three weeks at a dose of 60 mg per total body weight intravenously. The total dose of THP achieved was 720 mg in the first patient and 920 mg in the second. Despite the high dosage, neither cardiotoxicity nor alopecia was observed. These results suggest that the administration of THP may be efficacious and safe in the management of patients with recurrent gastrointestinal carcinoma.

Topics: Adenocarcinoma; Adult; Doxorubicin; Female; Humans; Injections, Intravenous; Liver Neoplasms; Male; Middle Aged; Neoplasm Recurrence, Local; Rectal Neoplasms; Stomach Neoplasms

A phase II study on THP((2''R)-4'-0-Tetrahydropyranyladriamycin) was performed in 47 patients with advanced or recurrent gastrointestinal cancer through the cooperation of nine institutions in Hiroshima Prefecture from April 1982 to November 1984. THP was given by means of intravenous infusion and/or intraaortic infusion and the 47 cases were divided into two groups according to the method of administration: (A) 40-60 mg/body every 3 or 4 weeks, or (B) 30 mg/body every week. Among 24 evaluable cases, partial response (PR) was observed in two cases of recurrent metastatic lymph nodes in gastric cancer patients. The (A) method of administration was more effective than (B). Subjective side effects observed were appetite loss, nausea, vomiting and general fatigue, but these were not so severe. Leukocyte nadir occurred at the 1st or 2nd week of THP administration, but thrombocytes were not appreciably decreased.

Topics: Antineoplastic Agents; Colonic Neoplasms; Doxorubicin; Drug Administration Schedule; Drug Evaluation; Humans; Infusions, Intra-Arterial; Infusions, Parenteral; Liver Neoplasms; Rectal Neoplasms; Stomach Neoplasms

THP-ADM is a new antitumor agent which belongs to the anthracycline family. This agent has shown a high therapeutic index compared with the mother compound, Adriamycin, in preclinical and clinical studies. This time, a pharmacokinetic study of THP-ADM was performed and the following characteristics of this agent were clarified. Short t1/2 was noted compared with that of Adriamycin in a 3-compartment open model. Leukocyte concentration of THP-ADM was much higher than that of plasma or red blood cells. Renal excretion over 48 hours was 9% and biliary excretion over the same period was 20%. Tissue concentration revealed high THP-ADM and low Adriamycin in all tissues excluding the liver. In liver tissue, a high concentration of Adriamycin and a low concentration of THP-ADM was observed. A small amount of Adriamycin was noted in the plasma following THP-ADM administration. The Adriamycin was most likely related to the small amount of existing Adriamycin in THP-ADM or conversion of THP-ADM to Adriamycin in the liver tissue or both. Poor penetration of THP-ADM was noted into the third space.

Topics: Doxorubicin; Humans; Kinetics; Liver; Liver Neoplasms; Neoplasms; Stomach Neoplasms

A phase I trial of a new anthracycline derivative, 4'-O-tetrahydropyranyldoxorubicin (THP), was conducted in 54 patients with various advanced solid tumors and malignant lymphomas. Starting dose was 5 mg/m2 i.v. and dose escalations were made by a modified Fibonacci search scheme. There were 40 evaluable courses. The dose-limiting toxic effect was leukopenia which was dose-related and reversible. The maximum tolerated dose for a single i.v. injection was estimated to be 55 mg/m2. The median nadir day for leukopenia was day 12 with recovery occurring 13 days (median) after reaching the nadir. Thrombocytopenia was less commonly observed than leukopenia. Other toxic effects were mild gastrointestinal disturbances, fever and general malaise. Ventricular extrasystole was observed in a case of pancreatic cancer who received 5 mg/m2 of the drug. There were no cases with alopecia, or with hepatic or renal dysfunction. With regard to objective tumor response, CR was observed in 2 cases with NHL, and MR in 2 cases with lung cancer, and 1 case each with breast cancer and NHL. Response occurred at a dose of more than 35 mg/m2. The recommended dose schedule for phase II trial is 35-45 mg/m2 by single i.v. injection at 3-4-week intervals.

Topics: Aged; Anorexia; Breast Neoplasms; Doxorubicin; Drug Administration Schedule; Drug Evaluation; Female; Humans; Infusions, Parenteral; Leukopenia; Lung Neoplasms; Lymphoma; Male; Middle Aged; Nausea; Neoplasms; Stomach Neoplasms; Thrombocytopenia

A phase II study of a new anthracycline, (2''R)-4'-0-tetrahydropyranyladriamycin (THP) was performed on 37 patients with gastrointestinal cancer in 6 co-operative study institutions. Twenty-five patients out of 37 were evaluable for response according to the Koyama-Saito's criteria. THP was administered weekly at doses of 10 to 30 mg/body or every 3 to 4 weeks at doses of 40 to 60 mg/body intravenously. Of the 14 patients with gastric cancer, we obtained one complete response and 3 partial responses (response rate 28.6%), and of the 6 patients with rectal cancer, we obtained one partial response (16.7%). Leukopenia of less than 3 X 10(3)/mm3 and erythrocytopenia of less than 300 X 10(4)/mm3 were seen in 48% and 26% of cases. Neither cardiotoxicity nor hair loss were seen. These results suggest that THP is useful in the treatment of patients with gastrointestinal cancer.

Topics: Adult; Anorexia; Colonic Neoplasms; Doxorubicin; Drug Administration Schedule; Drug Evaluation; Female; Humans; Leukopenia; Male; Middle Aged; Nausea; Rectal Neoplasms; Stomach Neoplasms

A phase II clinical trial of a new anthracycline, 4'-O-tetrahydropyranyladriamycin (THP-ADM), was performed in thirty-one patients with advanced malignant tumors refractory to standard chemotherapies. The dosage of THP-ADM was 40 mg/m2 by iv bolus injection repeated every 3 weeks. Of 3 evaluable patients with non-Hodgkin's lymphoma, one achieved partial remission. A minor response was noted in one out of 7 patients with gastric cancer and one out of 5 patients with ovarian cancer. Leukopenia less than 4 X 10(3)/cmm and thrombocytopenia less than 100 X 10(3)/cmm were seen in 81% and 19% of cases, respectively. Mild gastrointestinal toxicities including nausea and vomiting and anorexia were observed in about one third of the patients. Mild hair loss occurred in 2 patients (6%). No ECG abnormalities on clinical sign of cardiotoxicity were seen.

Topics: Aged; Breast Neoplasms; Doxorubicin; Drug Administration Schedule; Drug Evaluation; Female; Humans; Lymphoma; Male; Middle Aged; Neoplasms; Ovarian Neoplasms; Stomach Neoplasms

THP-ADM is a new antitumor antibiotic which belongs to the anthracycline group. This agent was administered to 42 histology proven various malignant disease patients with a schedule of 60-80 mg per body (40-55 mg per m2) iv bolus, every three weeks. THP-ADM administration revealed mild upper GI toxicity (vomiting 19%, stomatitis 21%) and leukopenia (less than 2,000 per mm3) in 80% and thrombocytopenia (less than 60,000 per mm3) in 38% with good rebound. There was no signs or symptoms of cardiac failure including the patient who had received 740 mg per body (500 mg per m2). Definite response (CR, PR) was observed in ovarian carcinoma 4/11, cervix carcinoma 2/7, breast carcinoma 1/6, malignant lymphoma 5/5 and mesothelioma 1/2. Furthermore, some response (MR) was observed in lung metastasis from endometrial carcinoma 2/4, and stomach carcinoma 1/3. The above indicated usefulness of this agent and further study should be continued, especially a controlled study with adriamycin.

Topics: Adult; Aged; Antibiotics, Antineoplastic; Doxorubicin; Drug Evaluation; Female; Humans; Lymphoma; Male; Mesothelioma; Middle Aged; Ovarian Neoplasms; Sarcoma; Stomach Neoplasms; Uterine Cervical Neoplasms; Uterine Neoplasms