Combination chemotherapy with vincristine, epirubicin and cyclophosphamide in small cell lung carcinoma. Polish Lung Cancer Cooperative Group.

The aim of this prospective study was to assess the activity of a combination of vincristine, epirubicin and cyclosphosphamide (VEC) in previously untreated patients with limited small cell lung carcinoma (SCLC) and to delineate the feasibility of dose escalation for epirubicin in this regimen. The chemotherapy schedule included cyclophosphamide, 1000 mg/m2, vincristine, 1 mg/m2 and escalating doses of epirubicin: 50 mg/m2, 70 mg/m2 and 90 mg/m2; respectively in three consecutive groups of patients. Drug cycles were repeated every 3 weeks. 118 patients from eight institutions were enrolled in this study between February 1986 and March 1989. Objective tumour response was observed in 81 of 116 evaluable patients (70%) including 25 patients (22%) who achieved a complete remission. Responding patients received thoracic radiation after the fourth cycle of chemotherapy. The median duration of response was 30 weeks and the median duration of survival was 52 weeks. There were no significant differences in treatment results between the consecutive groups of patients. The regimen was well tolerated for all doses of epirubicin. The main toxicities included alopecia (96%), nausea and vomiting (81%) and leukopenia (44%). Grade 4 haematological toxicity was observed in 3 patients (2.6%). No significant epirubicin dose-dependent side effects, except for mucositis were observed.

Combination chemotherapy with cyclophosphamide, epirubicin and etoposide in small cell lung cancer.

From March 1987 to February 1991, 136 patients with untreated small cell lung cancer (64 patients with limited disease and 72 with extensive disease), were treated as part of a prospective multi-center study, with a combination of cyclophosphamide 1000 mg/m2 i.v. on day 1, epirubicin 70 mg/m2 i.v. on day 1 and etoposide 100 mg/m2 i.v. on days 1, 3 and 5. Courses were repeated every 3 weeks. One-hundred thirty-four patients were evaluable. There were 42 (31%) complete responses and 66 (49%) partial responses for an overall response rate of 80% (95% confidence interval 71-87%). A complete response was seen in 24 patients (38%) with limited disease and in 18 patients (26%) with extensive disease, while a partial response was observed for 31 (48%) and in 35 (50%) patients, respectively. The median duration of response for all patients was 8.9 months (range, 1-60+ months). The median duration of survival for the entire group was 11.4 months (12.5 months for limited disease and 9.8 months for extensive disease). The 2-year survival rate for the whole group was 13%. The main side-effects were myelosuppression, alopecia, nausea and vomiting. Grade 4 toxicity was seen in 8.5% of patients. In conclusion, the studied regimen was found to be active and well tolerated and may be considered as an alternative to standard chemotherapy combinations in SCLC.

Does chemotherapy-induced leukopenia predict a response in small-cell lung cancer?

The correlation between chemotherapy-induced toxicity and treatment outcome in cancer patients has not been studied thoroughly. Our aim was to evaluate whether there is any relationship between chemotherapy-induced leukopenia and response to treatment in small-cell lung cancer (SCLC). Data derived from records of 228 patients treated within two prospective multicentre phase II studies were analysed. In the first study (101 patients) chemotherapy included vincristine, epirubicin and cyclophosphamide and, in the second (127 patients), cyclophosphamide, etoposide and epirubicin; both regimens were given every 3 weeks. In the present analysis, the correlation between treatment outcome (response rate and survival) and highest scores of leukopenia within the first two and up to the fourth chemotherapy cycle, respectively, was evaluated. The objective response rate for the entire group was 66%; 53% in patients whose white blood cells remained normal and 85% in those who developed leukopenia within the first two cycles (P = 0.000). In multifactorial analysis, also including other treatment- and patient-related factors, independent correlation with response to chemotherapy was found for leukopenia (P = 0.001), chemotherapy regimen (P = 0.002) and the combined relative dose intensity (P = 0.018), but not for patient sex, age, performance status, pre-study weight loss, extent of disease and initial white blood cell count. Leukopenia within the first two cycles of chemotherapy was not correlated with survival, whereas such correlation for leukopenia occurring up to the fourth cycle was at the borderline level (P = 0.06). These findings suggest a relationship between chemotherapy-induced leukopenia and tumour response in SCLC.

[The role of aromatic hydrocarbon hydroxylase in the pathogenesis of lung cancer]. / Rola hydroksylazy weglowodorów aromatycznych w patogenezie raka pluca.

Aromatic hydrocarbons hydroxylase (AHH)--an enzyme of monooxydases group--catalyzes hydroxylation of polycyclic aromatic hydrocarbons yielding compounds of the direct cancerogenic properties. Inducibility determined genetically is a characteristic feature of AHH. Inducibility of AHH in patients with cancer of the lungs is higher than that in healthy population. According to some authors general population may be classified into three groups of : high, moderate, and low degree of AHH inducibility. A significant increase in the incidence of neoplasms related to an exposition to PAH was noted in patients with increased AHH inducibility. These neoplasms include: carcinoma of the lungs, mouth and larynx, cancer of the pharynx and leukoplakia. Moreover, the onset of these neoplasms is earlier than in subjects with moderate and low inducibility of AHH.