A phase II study of cisplatin and 5-fluorouracil with concurrent hyperfractionated thoracic radiation for locally advanced non-small-cell lung cancer: a preliminary report from the Okayama Lung Cancer Study Group

Abstract

A recent meta-analysis and randomized studies have demonstrated that combined chemoradiotherapy is associated with a survival advantage for selected patients with locally advanced unresectable non-small-cell lung cancer (NSCLC). We conducted a phase II study of combined chemoradiotherapy to find a more effective combination of drugs and radiation than those previously reported for such patients. Between January 1994 and November 1996, 50 previously untreated patients with locally advanced unresectable NSCLC (stage IIIA with N2 or IIIB disease) were entered in this study. Patients were required to have Eastern Cooperative Oncology Group performance status ≤ 2, age ≤ 75 years and adequate organ function. Treatment consisted of three cycles of cisplatin (20 mg m−2, days 1–5) and 5-fluorouracil (5-FU) (500 mg m−2, days 1–5) every 4 weeks, and concurrent hyperfractionated thoracic radiation (1.25 Gy twice daily, with a 6-h interfraction interval; total radiation dose, 62.5–70 Gy). Of the 50 patients entered, 37 (74%) responded to this chemoradiotherapy, including two (4%) with complete response. By a median follow-up time of 41.0 months, 35 patiennts had died and 15 were stil alive. The median time to progression for responding patients was 14.1 months (range, 2.6–51.3+ months). The median survival time was 18.7 months, with a survival rate of 66.0% at 1 year, 46.0% at 2 years and 27.6% at 3 years. Survival outcome was strongly affected by the extent of nodal involvement (median survival time, 27.4 months for N0–2 disease (n = 37) vs 10.7 months for N3 disease (n = 13);P = 0.007). The major toxicities of treatment were leukopenia and neutropenia (≥ Grade 3, 58% and 60% respectively). Other toxicities of ≥ Grade 3 included thrombocytopenia (26%), anaemia (26%), nausea/vomiting (16%) and radiation oesophagitis (6%). Treatment-related death occurred for one patient. Our findings suggest that cisplatin and 5-FU in combination with concurrent hyperfractionated thoracic radiation is effective and feasible for the treatment of locally advanced unresectable NSCLC. The short-term survival in this study appeared to be more encouraging than those of similar chemoradiation trials. A randomized trial will be needed to compare the combination of cisplatin and 5-FU with other platinum-based regimens together with concurrent hyperfractionated thoracic radiation. In addition, in future studies, inclusion criteria for N3 disease with or without supraclavicular involvement should be reconsidered to correctly evaluate the effect of combined chemoradiotherapy for locally advanced unresectable NSCLC. © 2000 Cancer Research Campaign

Long-term survival results of non-small cell lung cancer patients with complete pathological response after neoadjuvant therapy

“…In particular, patients who had regression in N 2 disease and underwent complete resection are reported to have better prognosis. [3][4][5][6][7][8][9] The issue is to be able to clearly detect the nodal status preoperatively and the degree of the response to the neoadjuvant treatment regimen. It is mandatory to perform PET/CT and evaluate the results and obtain samples from the nodal involvement areas using invasive methods.…”

“…Patients that received high dose radiotherapy in addition to chemotherapy are reported to have complete pathological response rates up to 55%. [5][6][7][8][9][18][19][20][21][22][23][24][25][26] Pathologically complete or near complete response is reported to be a prognostic factor by some authors. [10][11][12][13][14] Although prognosis is preferably good in this group of patients, distant recurrences in particular may reduce success rates.…”

“…However, the generally accepted opinion is that patients who have no findings of N 2 disease and who undergo complete resection benefit the most. [3][4][5][6][7][8][9] Various studies have demonstrated that a pathologically complete or near complete response is also one of the important prognostic factors. [10][11][12][13][14] There is no certainty about the evaluation of complete response after treatment.…”

Second primary cancer in survivors following concurrent chemoradiation for locally advanced non-small-cell lung cancer

“…We previously reported the 2-or 3-year survival outcomes of two concurrent CRT regimens in surgically unresectable stage III NSCLC (Segawa et al, 2000;Kiura et al, 2003). Here we report longterm results on cause of death and analysis of SPC in these two trials with a minimum follow-up period of 5 years.…”

Phase I/II study of docetaxel and cisplatin with concurrent thoracic radiation therapy for locally advanced non-small-cell lung cancer

“…Several studies and meta-analyses have documented an improvement in patients with stage III disease treated with chemotherapy followed by thoracic radiation therapy, compared with radiation therapy alone (Marino et al, 1995;Dillman et al, 1996;Sause et al, 2000). Full-dose cisplatin-based chemotherapy with concurrent thoracic radiation therapy produced encouraging results with relatively severe toxicities (Lee et al, 1996;Reboul et al, 1996;Segawa et al, 2000).…”