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BACKGROUND Lonidamine (LND) is an indazol-carboxylic acid derivative that selectively inhibits the energy metabolism of neoplastic cells, and increases the permeability of cell membranes. In vitro studies have demonstrated that LND can potentiate the oncolytic activity of cytotoxic drugs and is able to reverse the acquired multidrug resistance of neoplastic cells. Some clinical trials have suggested a synergism of LND with alkylating agents, cisplatin, and anthracyclines in various solid tumors. METHODS From June 1990 to June 1993, 158 previously untreated patients with Stage IIIB and IV nonsmall cell lung cancer (NSCLC) were enrolled into a multicentric randomized trial to evaluate the addition of LND to a cisplatin-epirubicin-vindesine regimen. Eighty patients in the control arm (A) received cisplatin, 60 mg/m2 intravenously (i.v.); epirubicin, 60 mg/m2 i.v.; and vindesine, 3 mg/m2 i.v. (PEV), on Day 1 every 4 weeks, whereas 78 patients in the experimental arm (B) received the same regimen with the addition of LND from 75 mg orally three times on Day 1 to 150 mg orally three times on Day 7+ until tumor progression occurred. RESULTS The experimental treatment achieved a significantly higher proportion of major responses in comparison with the control regimen (43% vs. 24%; P = 0.02). The addition of LND apparently potentiated the activity of this cytotoxic treatment, particularly in patients with metastatic disease (overall response rate, 39% vs. 17%). The median time to progression (5 vs. 8 months; P = 0.0007) and the median survival time (7.6 vs. 11 months; P = 0.0013) were also statistically improved in Arm B. The acute toxicity of the 2 treatments was low: only 6% of patients in Arm A and 4% of patients in Arm B had to withdraw from treatment due to Grade 4 World Health Organization toxicity. The main additional side effects related to the administration of LND were epigastralgia, myalgia, asthenia, and orchialgia. However, these symptoms were mild and controlled by the concomitant administration of low doses of steroids. CONCLUSIONS The mild acute toxicity of the PEV regimen and the acceptable and nonoverlapping additional side effects of LND render our experimental therapy worthy of consideration for the management of NSCLC patients with poor performance status or low tolerance to more aggressive therapeutic approaches. Cancer 1996;78:63-9.

To estimate the safety, activity, and impact on quality of life of a combination of gemcitabine and pemetrexed in patients with locally advanced or metastatic non-small cell lung cancer (NSCLC) in the context of a randomized two-stage phase II study.Patients in stage IIIB or IV NSCLC were randomly allocated to receive either gemcitabine 1250 mg/m(2) on day 1, and pemetrexed (Alimta) 500 mg/m(2) followed by gemcitabine 1250 mg/m(2) on day 8 of a 3-weekly cycle (GA arm), or paclitaxel 120 mg/m(2) followed by gemcitabine 1000 mg/m(2), both given on days 1 and 8 of a 3-weekly cycle (PG arm).105 (GA arm, 51; PG arm, 54) eligible patients (stage IV, 32 and 30, respectively) were enrolled into this study; thereafter, accrual was stopped due to first-stage analysis. The response rate was 20% (95% confidence interval [CI], 10-33%) in the GA arm, and 32% (95% CI, 20-46%) in the PG arm. Median progression-free survival was 5.1 (95% CI, 3.7-6.5) months in the GA arm, and 8.3 (95% CI, 5.9-10.7) months in the PG arm, while median overall survival was 10.5 (95% CI 7.1-13.9), and 13.3 (95% CI 11.7-14.9) months, respectively. Severe neutropenia (36% vs 22%), and febrile neutropenia (14% vs 7%) were more common with the GA regimen, while hair loss (52% vs 16%) and any grade peripheral neuropathy (31% vs 2%) occurred more frequently with PG regimen. Other severe side effects of GA regimen were diarrhoea (10%), liver enzyme derangement (10%), and fatigue (8%).The GA regimen was tolerated and moderately active in advanced or metastatic NSCLC. However, this combination did not yield any advantage in comparison with the PG regimen, and does not deserve further evaluation.

OBJECTIVE. We report our preliminary evaluation of the effectiveness, safety, technical feasibility, and complications of palliative CT-guided radiofrequency ablation of unresectable primary pulmonary malignancies. SUBJECTS AND METHODS. Thirty-three patients (26 men and seven women; age range, 44-75 years; mean age, 66 years) with unresectable malignant lung neoplasms underwent 35 CT-guided tumor ablation sessions. Follow-up CT was performed 6 months (29 cases) and 1 year (10 cases) after treatment. In 19 patients, these findings were correlated with cytohistopathologic assessment obtained with CT-guided fine-needle aspiration biopsy or core biopsy at 6-month follow-up. Size and CT appearance of the treated lesions were correlated with cytohistologic features and clinical scores. RESULTS. Thirty-five technically successful radiofrequency ablation treatments were performed. The only complications in the periprocedural period were three cases of minor pneumothorax, five cases of sputum cruentum, and three asymptomatic pleural effusions. Contrast-enhanced CT performed at 6-month follow-up showed four cases of complete and 13 cases of partial lesion ablation, 11 cases of stabilized lesion size, and one case of increased lesion size. Contrast-enhanced CT performed at 1-year follow-up showed unchanged lesion size in six cases and reduction in four cases. Six-month cytohistologic examinations showed total coagulation necrosis in seven lesions and partial necrosis in 12. Clinical improvement in pretreatment symptoms was observed in 12 of 29 patients seen at 6-month follow-up. Eight patients died within 1 year of treatment of non-procedure-related causes. CONCLUSION. Our experience suggests that radiofrequency ablation can be used successfully in unresectable lung cancer as an alternative or complementary treatment to radio-or chemotherapy. Larger studies are necessary to fully evaluate its potential combination with other treatment techniques.