pirarubicin and Carcinoma--Small-Cell

Topics: Antibiotics, Antineoplastic; Breast Neoplasms; Carcinoma, Non-Small-Cell Lung; Carcinoma, Small Cell; Clinical Trials, Phase I as Topic; Doxorubicin; Female; Head and Neck Neoplasms; Humans; Lung Neoplasms; Lymphoma; Mesothelioma

The usual form of chemotherapy of metastatic small cell lung cancer gives a 50% objective response with a mean survival of 7-8 months. We have tested a new antimitotic drug using pirarubicin alone in 26 patients. After the second treatment we noticed a response level of 12% with moderate toxicity. Then, we undertook classical chemotherapy using cisplatin-V16. After 3 doses the response level was 50% with a median survival of 32 weeks. In our study the use of a single drug pirarubicin in metastatic small cell cancer did not appear to worsen the chance of survival in patients if polychemotherapy was carried out immediately in cases which failed on the single drug. Our monotherapy did not appear to induce resistance to affective polychemotherapy. This method applied carefully to patients with metastatic disease with a strict follow up may be utilised in the assessment of the efficacy of the newer antimitotic drugs.

Topics: Adult; Aged; Antibiotics, Antineoplastic; Antineoplastic Combined Chemotherapy Protocols; Carcinoma, Small Cell; Cisplatin; Doxorubicin; Etoposide; Female; Humans; Lung Neoplasms; Male; Middle Aged; Neoplasm Invasiveness; Remission Induction; Survival Rate

The toxicity and efficacy of the combination of pirarubicin (THP), etoposide, and vincristine were investigated in a phase I trial. The dose of THP was modified in steps of 10 mg/m2 or 5 mg/m2 differences, starting with 40 mg/m2 i.v. on day 1. Doses of etoposide (100 mg/m2 i.v. days 1-3) and vincristin 2 mg i.v. day 1) remained constant. The schedule was repeated every 3 weeks. A minimum of four patients were recruited at each dose level. The maximum tolerated dose (MTD) was defined as follows: toxicity WHO grade 3 and 4 in five of eight patients of one dose step (exception: leukocytopenia at the time of nadir WHO grade 4 is relevant for the MTD). Currently, 20 patients have been treated. The administered dose levels of THP were (mg/m2); 40 (5 patients), 50 (4 patients), 55 (6 patients), and 60 (5 patients). Screening of cardiac function (ECG, ultrasound cardiography) was performed at the start of the treatment and before each course. There were no signs of cardiotoxicity up to a cumulative dose of 360 mg/m2. Leukocytopenia WHO grade 3 was observed in seven courses (12%), and grade 4 was observed in two courses (3%) as main side effects. The subjective tolerability (nausea, vomiting, and alopecia) was mild to moderate. We decided upon 55 mg/m2 MTD because WHO grade 4 leukocytopenia developed in one patient after the first course and two not conclusively clarified early deaths occurred at the 60 mg/m2 pirarubicin dose level. Eighteen patients were evaluable for response: one CR (6%), eight PR (44%), four NC (22%), one EP (6%), and four ED (22%). This means a response rate of 50% and a median survival time of 10 months. We have initiated a phase II study with the elaborated schedule.

Topics: Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Carcinoma, Small Cell; Doxorubicin; Drug Evaluation; Etoposide; Female; Humans; Lung Neoplasms; Male; Middle Aged; Remission Induction; Survival Rate; Vincristine

Pirarubicin (THP) (Roger Bellon Laboratory, France) is a new anthracycline under clinical development. In order to assess the efficacy and toxicity of the drug in small-cell lung carcinoma (SCLC), we have undertaken this trial in front-line therapy in patients with metastatic disease, PS less than 3 and at least one evaluable lesion. Responses were assessed after two cycles of THP (60 mg/m2 i.v. bolus every 3-4 weeks) and a further cross over to VP16 + CDDP (three cycles) was systematic whatever the response to THP. This crossover was performed after only one cycle in case of obvious progression. From June 1988 to April 1990, 32 patients were enrolled: 6 were ineligible (4 non-SCLC, 2 M0), 26 patients were fully evaluable for THP and 18 patients for VP16-CDDP. The characteristics of the patients were as follows: mean age 57.4 years (38-71); T4: 54%; T3: 27%; T2: 19%; N3: 62%; N2: 35%; No: 4%. The efficacy was as follows 1 complete response and 2 partial responses (confirmed by endoscopy); 12 patients received only one cycle because of obvious progression; the overall response rate is 12% (95% confidence interval 0-24%). The patient who had complete response after pirarubicin remained in CR after VP16-CDDP, whereas the 2 patients who had partial response achieved CR for one and PR for the other; among the 15 who did not respond 1 CR and 7 PR were observed. The only significant toxicity of THP was granulopenia without infection. THP seems to be an effective anthracycline in SCLC, and the study is continuing. A response could be reached in 50% of the nonresponders with standard therapy and 10 of 24 patients (42%) finally responded. Therefore, this schedule for testing new drugs in metastatic SCLC appears ethically acceptable.

Topics: Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Carcinoma, Small Cell; Cisplatin; Doxorubicin; Drug Administration Schedule; Drug Evaluation; Etoposide; Female; Humans; Lung Neoplasms; Male; Middle Aged; Neoplasm Staging; Remission Induction; Survival Rate

Between April 1984 and March 1988, a comparative randomized phase II study was performed to compare the effects of (2''R)-4'-0-Tetrahydropyranyl-adriamycin (THP) and adriamycin in combination with vincristine (VCR) and ACNU in 60 previously untreated and evaluable patients with small cell lung cancer (SCLC). Arm AVA was constituted by adriamycin, VCR and ACNU, and arm TAVA by THP, VCR, ACNU. Of the 30 patients treated with AVA, there were 20 partial responses, 7 with no change and 3 with progressive disease, for an overall response rate of 66.7%. On the other hand, of the 30 patients on TAVA, one complete response and 22 partial responses were observed, for an overall response rate of 76.7% Median survival time of AVA was 10.0 M, that, of TAVA was 9.3 M. But significant differences between the two arms was not found. During induction therapy, leukopenia was the main side effect. Over WHO Grade 3 leukopenia was seen in 53.3% of patients on AVA and 70.0% of those on TAVA. Moderate hair loss (Grade 2) was significantly less frequent with TAVA than AVA. In conclusion, the results indicated that THP is active in SCLC with the same level of adriamycin, and has less toxicity. THP is a suitable drug as a first line combination chemotherapy for SCLC.

Topics: Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Carcinoma, Small Cell; Doxorubicin; Drug Evaluation; Female; Humans; Lung Neoplasms; Male; Middle Aged; Nimustine; Random Allocation; Vincristine

A 67-year-old man, who was nephrectomized due to renal cell cancer 4 years ago, was admitted to examine a mass shadow in the right middle lung field. He was diagnosed as small cell lung cancer with TBLB. Because of impaired renal function, he was treated with CBDCA (300 mg/m2, day 1), THP (30 mg/m2, day 1) and oral etoposide (25 mg/body, for 21 days) without any renal complications. After 3 courses of chemotherapy, the lung CT showed scar lesion despite the disappearance on the chest X-ray, and a right lower lobectomy was performed. Malignant cells remained in the scar lesion, but not in the lymph nodes. These findings suggested the effectiveness of neoadjuvant chemotherapy. This newly-designed chemotherapy procedure is necessary for patients with renal complications.

Topics: Aged; Antineoplastic Combined Chemotherapy Protocols; Carboplatin; Carcinoma, Renal Cell; Carcinoma, Small Cell; Chemotherapy, Adjuvant; Doxorubicin; Etoposide; Humans; Lung Neoplasms; Male; Neoplasms, Second Primary; Nephrectomy

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

Topics: Carcinoma, Small Cell; Doxorubicin; Drug Evaluation; Lung Neoplasms

Sixteen untreated patients with small cell lung cancer were treated with a combination of Etoposide (70 mg/m2 i.v., day 3-5), Cisplatin (40 mg/m2 i.v., days 1 and 8) and THP (20 mg/m2 i.v., days 1 and 8). Cycles were repeated every 4 weeks and 15 patients received more than two cycles. The objective response rate was 80% (12 of 15) in complete cases, 91% (10 of 11) in limited disease and 50% (2 of 4) in extensive disease. CR rate was 33% in complete cases, 46% in limited disease. The median duration of response was 22.6 weeks. The median survival was more than 12 months in complete cases. Toxicity was primarily myelosuppression. Three of 15 patients had leukopenia of grade 4, 3 of 15 of grade 3, and 7 of 15 of grade 2. Nausea and vomiting were well tolerated by metoclopromide and methylprednisolone. The renal toxicity was minimal. There were no chemotherapy-related lethal complications. This schedule of Etoposide, split-dose Cisplatin and THP is effective and safe for patients with small cell lung cancer. However, the advantage of THP is still controversial.

Topics: Antineoplastic Combined Chemotherapy Protocols; Carcinoma, Small Cell; Cisplatin; Doxorubicin; Drug Administration Schedule; Etoposide; Humans; Lung Neoplasms; Pilot Projects; Survival Rate

Four human lung small cell carcinoma (SCC) cell lines were used for the experimental cancer chemotherapy with a single agent and combination method. The chemosensitivity of SCC cell lines including H-69, H-128, Lu-24 and Lu-134 were assessed by the clonogenic assay according to the method of Salmon and Humburger. Cyclophosphamide (CPA) showed the most excellent antitumor effect against these 4 strains followed by tetra-hydropyranyl adriamycin and adriamycin (ADM). In vitro combination clonogenic assay was conducted by mixing the half of the concentration of two matched drugs and the synergistic effect was evaluated according to the method of Berenbaum. Whereas the synergistic effects were frequently observed in the combination of drugs which were effective by the single usage, it was found that the combination of CPA + mitomycin C and CPA + ADM showed high efficacy rates against these cell lines in comparison with other matchings. From these findings, it was concluded that the combination chemosensitivity test in clonogenic assay might be a promising method to evaluate the chemosensitivity of the individual patient. And it was supposed that this method might be also useful as an early phase III study to predict the useful combination of newly developed antitumor agents.

Topics: Antineoplastic Combined Chemotherapy Protocols; Carcinoma, Small Cell; Cyclophosphamide; Doxorubicin; Drug Resistance; Humans; In Vitro Techniques; Lung Neoplasms; Tumor Cells, Cultured; Tumor Stem Cell Assay