A Phase 3 randomized trial of immediate combination chemotherapy vs delayed combination chemotherapy in patients with completely resected stage II and III non-small cell carcinoma of the lung

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Date: Dec. 1994
From: Chest(Vol. 106, Issue 6)
Publisher: Elsevier B.V.
Document Type: Article
Length: 2,089 words

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The purpose of this trial (Lung Cancer Study Group [LCSG] 853) was to perform a comparative study of immediate combination chemotherapy (cyclophosphamide, doxorubicin, cisplatin [CAP]) vs delayed combination chemotherapy (CAP) administered at the time of first systemic relapse in patients with completely resected stage II and stage III non-small cell cancer of the lung. We randomly assigned 188 patients with resected stage II or stage III non-small cell lung cancer of the lung (squamous, 53%; nonsquamous, 47%) to receive either immediate or delayed combination chemotherapy. Careful intraoperative staging was performed in all patients. Before randomization, patients were stratified according to stage--II (hilar nodes positive) vs III (mediastinal nodes positive or T3)--and histologic features (squamous vs nonsquamous). Ninety-four patients were randomized to receive immediate CAP vs 94 patients randomized to receive delayed CAP. Prognostic variables such as extent of disease, histologic features, sex, race, TN status, and Karnofsky performance status were equally distributed between randomized groups. The treatment groups differed with respect to greater than 10% weight loss. Forty-one percent of patients had stage II disease and 59% of patients had stage III disease. Median time to recurrence (19.5 months) and survival (32.7 months) did not differ between treatment groups. Immediate combination chemotherapy was associated with a 12% reduction in risk of recurrence and an 18% reduction in risk of death, although these rates were not statistically significant. Histologic features, sex, race, Karnofsky performance status, nodal status, and weight change were associated with higher risks of recurrence.

The prognosis for patients with lung cancer treated for curative intent with pulmonary resection is well defined for patients with clinicopathologically staged disease.(1)(2)(3)(4)(5) The 5-year survival rate is little better than 50% for the most favorable stage and the prognosis is worst for patients with regional lymph node metastasis or large tumors. In most patients, the first site of recurrence is systemic. The Lung Cancer Study Group (LCSG) has carried out a series of adjuvant trials in patients with carefully staged completely resected stage II and III non-small cell carcinoma of the lung treated with adjuvant chemotherapy, radiation therapy, or their combination.

In 1977, the LCSG began a prospective randomized trial of completely resected stage II and stage III adenocarcinoma and large cell undifferentiated carcinoma of the lung comparing combination chemotherapy, including cyclophosphamide, doxorubicin (Adriamycin), and cisplatin (CAP) with an immunotherapy control arm.(6) The conditions of all patients were staged by careful intraoperative node sampling. Patients were stratified by stage, weight loss, cardiac function, and institution, and prognostic variables were equally distributed between the two groups. Disease-free survival was prolonged in the group receiving chemotherapy, yet the overall survival did not reach statistical significance.

At about the same time, the LCSG was evaluating the effects of postoperative mediastinal irradiation on completely resected stage II and III squamous cell carcinoma of the lung.(7) Two hundred thirty patients with completely resected squamous cell carcinoma were randomized following surgery to a no-treatment observation arm or to receive mediastinal irradiation consisting of 50 Gy in 5 to 5...

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Gale Document Number: GALE|A16280579