peplomycin and Stomach-Neoplasms

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

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

The chemosensitivity of various head and neck cancers was investigated with the 5-day rapid thymidine incorporation assay in soft agar culture. The evaluability rate was 56%. Head and neck cancers were sensitive in vitro, in decreasing order, to peplomycin, cisplatin, bleomycin, 5-fluorouracil, mitomycin C, and doxorubicin. Primary tumors and neck metastases exhibited the same sensitivity, with 21% of all specimens tested responding. In vitro chemosensitivities were similar among patients younger than 69 years of age and those older than 70. The predictive accuracy for sensitivity tested prospectively in five cases was 80% and that for resistance in four was 75%.

Topics: Aged; Antibiotics, Antineoplastic; Antineoplastic Agents; Bleomycin; Child; Cisplatin; Colonic Neoplasms; DNA, Neoplasm; Doxorubicin; Drug Screening Assays, Antitumor; Fluorouracil; Head and Neck Neoplasms; Humans; Lymphatic Metastasis; Methotrexate; Middle Aged; Mitomycins; Peplomycin; Remission Induction; Stomach Neoplasms; Thymidine; Tritium; Tumor Cells, Cultured

This study was designed to establish a model able to predict the clinical efficacy of anticancer agents against cancers of specific organ. Seven weeks old, male BALB/c nude mice were implanted with 1 X 10(6) cells of human gastric cancer G/F into either their subcutis or the stomach wall. Fourteen days after the implantation, the mice were injected daily once for 10 days with peplomycin or mitomycin C. Peplomycin was effective on the subcutaneous tumors with an inhibition rate of 26 and 64% at doses of 1.5 and 6.0 mg/kg, respectively. Peplomycin was ineffective on the tumors in the stomach wall. Mitomycin C was ineffective on the subcutaneous tumors, but effective on the tumors in the stomach wall and the inhibition rate was 52 and 63% at doses of 0.13 and 0.5 mg/kg, respectively. Study on the distribution of peplomycin and mitomycin C to those tumors revealed that peplomycin and mitomycin C levels in the subcutaneous tumors were 2 to 7 times and about 3 times higher than those in the stomach wall, respectively. Thus, drug distribution could not explain the differences in drug sensitivity. The sensitivity of the tumor in the stomach wall to peplomycin and mitomycin C was consistent with the clinical efficacy of these drugs against human gastric cancers. This suggests that models where the tumors are implanted into its original organ are useful for predicting clinical efficacy in experimental cancer chemotherapy.

Topics: Adenocarcinoma; Animals; Bleomycin; Drug Screening Assays, Antitumor; Humans; Male; Mice; Mice, Inbred BALB C; Mice, Nude; Mitomycin; Mitomycins; Neoplasm Transplantation; Peplomycin; Skin; Stomach; Stomach Neoplasms

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

Topics: Aged; Antineoplastic Combined Chemotherapy Protocols; Bleomycin; Combined Modality Therapy; Cyclophosphamide; Female; Gastrectomy; Humans; Lymphoma; Male; Middle Aged; Peplomycin; Prednisone; Stomach Neoplasms; Vincristine