Anticipated administration of GM-CSF in the treatment of non small cell lung cancer.

The purpose of this study was to verify the kinetic response of the human marrow myeloid progenitor cells to the short term use of GM-CSF and its impact on the therapeutic activity of this three-drug cisplatinum containing regimen in non small cell lung cancer (NSCLC). Sixty patients with stage III-B and IV NSCLC were randomised to receive GM-CSF for 3 days, five days prior to the onset of chemotherapy. The chemotherapy regimen consisted of Mitomycin-C: 6 mg/m2 on day one, Ifosfamide: 2000 mg/m2 days 1 to 3, Mesna: 2000 mg/m2 days 1 to 3, Cisplatinum: 30 mg/m2 days 1 to 3, and was repeated every 4 weeks. All the patients received 30-50 Gy of radiotherapy to the primary and/or metastatic sites. There were positive correlations between stage of the disease, chemosensitivity of the tumor, number of chemotherapy cycles and overall survival (p=0.000). Administration of GM-CSF was an independent prognostic parameter in locally advanced and metastatic disease (p=0.041). In the GM-CSF receiving arm more courses could be given (117 versus 99, p=0.0415), and less courses were postponed (6 versus 22). In this arm, the mean of granulocyte nadir was higher (p=0.033) and mean time to granulocyte recovery became shorter (p=0.001) as the number of chemotherapy cycles increased. It was concluded that, dose intensification with GM-CSF prophylaxis is benefical in increasing the treatment tolerability by decreasing the intensity of granulocytopenia as well as providing rapid recovery.

Primary therapeutic decision-making in inoperable non-small cell lung cancer.

PURPOSE: To test the accuracy of our treatment decisions for patients with inoperable non-small cell lung cancer (NSCLC) using a prototype decision-support system (DSS) and a prognostic index (PI). METHODS AND MATERIALS: To predict patient outcome and select optimal treatment, the systems protocol was tested retrospectively in 242 patients with Stage I-IV disease. The PI was determined in 184 patients with Stage I-IIIa,b disease. Survival was the final determinant of the accuracy of our treatment decisions. RESULTS: Until 1996 it was our treatment policy to treat all Stage III patients with radical intent unless they had symptoms requiring palliation. In 1997, after the palliation concept of the DSS and the PI were changed to include all Stage III disease, there was considerable discordance between the rates of palliative treatment indicated by the DSS and the PI (69% and 99%, respectively) as well as that observed in our practice (30% in the DSS group and 20% in the PI group, respectively). There was also a significant difference in survival between the patients in the low- and high-risk categories defined by the PI (median survival of 12 versus 6 months, respectively; p = 0.0001). In the group that received radical radiotherapy, there was also a significant difference in the duration of survival between the low- and high-risk groups (median survival of 12 versus 8 months, respectively; p = 0.01). In addition, the risk categories proved to be the most important predictor of survival in the patients receiving radiotherapy longer than 2 weeks (median survival of 12 versus 7 months, respectively; p = 0.0001). In high-risk patients, however, the duration of radiotherapy did not have a significant impact on survival (p = 0.25). CONCLUSION: Our data indicate that the PI is a useful method for selecting radical or palliative treatment modalities as well as for determining treatment duration.

Supportive treatment in weight-losing cancer patients due to the additive adverse effects of radiation treatment and/or chemotherapy.

The reversal of anorexia and weight loss especially in patients with advanced cancer suffering from radiation treatment (RT) -related complications and debilitated furtherly during RT would be a welcome relief. The purpose of this study is to evaluate the feasibility of supportive treatment with megestrol acetate (MA) in our weight-losing cancer patients increasingly experiencing anorexia, smell, taste, and weight loss due to the additive adverse effects of RT +/- chemotherapy and how MA changes the additive role of the severity of RT reactions on such patients. From June 1997 to October 1998, 100 eligible patients were enrolled on a randomized, placebo-controlled clinical trial. Of the 100 patients, 46 received MA during RT and 4 after the end of the RT, and 50 received placebo for 3 months. Subjective parameters were assessed by a brief questionnaire form based on scoring from 1 to 5, according to the degree of the loss or change for each parameter of malnutrition, appetite, taste and smell developed by us. At the end of the study a statistically significant weight gain was achieved in the patient group receiving MA compared to the placebo group (+3 to +5 kg versus -3.7 to -5.9 kg, p=0.000). Significant improvements were seen in performance status (p=0.000), appetite (p=0.000), malnutrition (p=0.000), loss of taste (p=0.000) and smell qualities (p=0.02) in the MA group compared to the placebo group. In the MA group there was no statistically significant difference related to the weight changes according to the grade of either the acute or late RT effects (p=0.65 and 0.07, respectively). Whereas, in the placebo group a statistically significant additive effect of the acute and late RT effects was detected on weight loss (p=0.008 and 0.007, respectively). We observed no side-effects of MA in a 3-month time follow-up. The use of MA 480 mg/day during RT was effective in reversing anorexia and weight loss in spite of the acute RT effects, and helped most patients to well tolerate specific tumor therapy. Further evaluation of its mechanisms of action on RT-related adverse effects, tumor response relationships, and effect on patient survival are researched.

Impact of tumor stage, operative down-staging, tumor grade and radioresponsitivity of the tumor on survival in supratentorial astrocytomas.

This retrospective study analyzed specifically the predicting factors for radioresponse and survival in 74 supratentorial astrocytoma patients. As a result of this study, cytoreduction in terms of ODs to T1 or T0 stage level or pre-RT T1 tumor stage along with radioresponse has a positive impact on long-term survival. It seems that radical radiotherapy should be the choice of treatment for the patients who had pre-RT T0 and T1 disease who were found more likely to respond to radiotherapy. This has not been reported previously and needs to be confirmed in larger trials.

The use of recombinant human granulocyte colony-stimulating factor in combination with single or fractionated doses of ifosfamide and doxorubicin in patients with advanced soft tissue sarcoma.

Sixty patients with stage III-B and IV soft tissue sarcomas were randomized to receive either ifosfamide 5 g/m2xdx1 and doxorubicin 60 mg/m2xdx1 given every 3 weeks (arm A) or ifosfamide 1.8 g/m2xdx5 and doxorubicin 60 mg/m2xdx1 given every 4 weeks (arm B). Recombinant human granulocyte colony-stimulating factor (r-met Hu G-CSF: 250 micrograms/m2xd) was applied with a prophylactic intent to patients in arm A only. The response rate was higher in arm A patients (56% versus 33%, p = 0.03). In stage III patients, the complete response rate was significantly higher (53% versus, 13.3%, p = 0.01) and the duration of response was significantly longer in arm A (20 +/- 8.2 months versus, 13.4 +/- 7 months, p = 0.05). Chemotherapy related myelotoxicity and mucositis were also less frequent in this arm as a result of prophylactic r-met Hu G-CSF administration (p = 0.04, p = 0.003). It was concluded that single dose ifosfamide and doxorubicin combinations deserve further investigation under the cover of hematopoietic growth factors, particularly in patients with stage III soft tissue sarcomas.