Decline of posttreatment tumor marker levels after therapy of nonsmall cell lung cancer. A useful outcome predictor.

BACKGROUND: The assessment of treatment efficacy in nonsmall cell lung cancer (NSCLC) is limited by the lack of a clear association between clinical response and survival. The prognostic usefulness of treatment-induced tumor-marker declines in NSCLC has not been established. The authors investigated the prognostic significance of treatment-induced declination in tumor marker levels of carcinoembryonic antigen, CA 19-9, and CA 125 in a group of patients with NSCLC treated with a brief course of cisplatin-based chemotherapy. METHODS: Eighty-three patients with NSCLC enrolled on 2 related treatment protocols had pretreatment tumor-marker determinations. Patients were restaged 10 to 12 weeks after study entry, and clinical and marker responses were determined. RESULTS: Thirty-eight patients (46%) had elevated pretreatment tumor markers, 36 (42%) of whom were evaluable for both clinical and marker responses. Pretreatment, the latter 36 individuals had measurable or evaluable disease, and at least one elevated tumor marker (greater than twice normal); posttreatment, they had follow-up measurements of both parameters. Of the 36 patients, 8 had normalization of tumor marker levels, 13 had 50-99% marker level declination, and 15 had less than 50% or no declination. In the same group of 36 patients, there were, 1 patient with complete clinical response, 11 with partial response, 19 with stable disease, and 5 with progressive disease. Marker responses occurred with equal frequency in clinical responders and nonresponders. There was no association between clinical response and survival, but there was a strong association between marker response and survival. CONCLUSIONS: In patients with nonsmall cell lung cancer with elevated pretreatment tumor marker levels, treatment-induced marker level declination can be a surrogate indicator for survival.

Clinical experience with leucovorin and 5-fluorouracil.

Two trials of leucovorin (LV) and 5-fluorouracil (5-FU) in patients with metastatic colorectal cancer were done, both using a 3-day loading dose and then weekly doses to minimize toxicity. The first trial used LV administered by intravenous infusion with a constant dose of 5-FU 400 mg/m2, and the second trail used oral LV with increasing doses of 5-FU. In the first trail, 45 eligible patients (20 with and 25 without previous therapy) were treated. Toxicity usually consisted of diarrhea or weakness and was controlled by delaying or decreasing the 5-FU dose. Subjective responses occurred in 75% of patients but did not correlate with antineoplastic effect. Objective responses were seen in 36% and stabilization of disease in 31% of patients; these correlated with prolonged survival. Median survival was 8 months for patients with previous treatment and 10 for those without. Twelve-month survival was 32% and 40%, respectively. There was no correlation between the development of toxicity and response or survival. The second trial was conducted recently in cooperation with Duke University to determine toxicity and efficacy of oral LV with intravenous 5-FU before a randomized trial of this combination versus placebo with intravenous 5-FU. Eighteen patients were treated, and serum levels of folates were obtained on ten. First toxicity occurred at 5-FU doses ranging from 375 to 850 mg/m2, and consisted of diarrhea in nine, lethargy in seven, nausea/vomiting in four, dermatitis in four, conjunctivitis in two, hypersalivation in two, stomatitis in one, and profound granulocytopenia in one. Response rate was 35%, and stabilization was 35% with median survival of 14 months. Twelve-month survival was 56%.

Clinical experience with CF-FUra.

Two trials of CF-FUra in patients with metastatic colorectal cancer were performed, both using a 3 day loading dose and then weekly maintenance doses to minimize toxicity. The first trial used CF by IV infusion with constant dose of FUra 400 mg/m2, and the second trial used oral CF with escalating doses of FUra. In the first trial, 45 eligible patients (20 with and 25 without prior therapy) were treated. Toxicity usually consisted of diarrhea or weakness and was controlled by delaying or decreasing 5FU dose. Subjective responses occurred in 75% of patients but did not correlate with antineoplastic effect. Objective responses were seen in 36% and stabilization of disease in 31% of patients, and correlated with prolonged survival. Median survival was 8 months for patients with prior treatment and 10 for those without, and 12 month survival was 32% and 40%, respectively. There was no correlation between the development of toxicity and response or survival. The second trial was recently conducted in cooperation with Duke University to determine toxicity and efficacy of oral CP with IV FUra prior to a randomized trial of this combination versus placebo with IV FUra. Eighteen patients were treated and serum levels of folates were obtained on 10. First toxicity occurred at FUra doses ranging from 375 to 850 mg/m2, and consisted of diarrhea in 9, lethargy in 7, nausea/vomiting in 4, dermatitis in 4, conjunctivitis in 2, hypersalivation in 2, stomatitis in 1, and profound granulocytopenia in 1. Response rate was 35% and stabilization was 35% with median survival of 14 months and 12 month survival of 56%.