peplomycin and Carcinoma--Small-Cell

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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