Long-Term Results of a Trial of Concurrent Chemotherapy and Escalating Doses of Radiation for Unresectable Non-Small Cell Lung Cancer: NCCTG N0028 (Alliance).

INTRODUCTION: This phase I/II trial was designed to determine the maximally tolerated dose of thoracic radiotherapy as part of a combined modality approach. This report includes the long-term outcomes of patients treated on this study. The phase II portion was never completed, as RTOG-0617 opened before it was concluded. METHODS: In this study, the maximally tolerated dose was defined as 74 Gy of radiation in 37 fractions. Twenty-five patients with unresectable NSCLC were treated with 2-Gy daily fractions and concurrent weekly carboplatin and paclitaxel. Of these patients, 20 had stage III disease and five had stage I or II disease. RESULTS: Patients were followed until death or for a minimum of 5 years in the case of survivors. The median and 5-year survivals were 42.5 months and 20% for all patients, 52.9 months and 40% in patients with stages I or II disease, and 39.8 months and 15% in patients with stage III disease. CONCLUSIONS: The median survival of the stage III patients was quite favorable. We believe that this may have been due to a robust central review program of radiotherapy plans before treatment, ensuring compliance with protocol guidelines along with very low exposure of the heart to radiotherapy. Further improvements in 5-year survival will likely require research on both systemic therapy and thoracic radiotherapy. Potential therapeutic modalities that may aid in these efforts include immunotherapy, targeted therapy, improved imaging, adaptive radiotherapy, simultaneous integrated boost techniques, novel dose fractionation regimens, and charged particle therapy.

Results of a Phase I trial of concurrent chemotherapy and escalating doses of radiation for unresectable non-small-cell lung cancer.

PURPOSE: This trial was performed to determine the maximum tolerated dose (MTD) of radiation that can be administered with carboplatin and paclitaxel. METHODS AND MATERIALS: This trial included 15 patients with unresectable non-small-cell lung cancer. Paclitaxel (50 mg/m2) and carboplatin (area under the curve=2) were given weekly during radiation therapy (RT). The RT included 2 Gy daily to an initial dose of 70 Gy, and the dose was increased in 4 Gy increments until determining the MTD. The MTD was defined as the highest safely tolerated dose where at most 1 patient of 6 experienced dose-limiting toxicity (DLT) with the next higher dose having at least 2 of 6 patients experiencing DLT. Three-dimensional treatment planning techniques were used without prophylactic nodal RT. RESULTS: Two patients were not evaluable because they did not receive therapy according to the protocol. No DLTs occurred in the 3 patients who received 70 Gy, 1 DLT occurred in the 6 patients who received 74 Gy, and 2 DLTs occurred in the 4 patients who received 78 Gy. The DLTs included Grade 3 pneumonitis (n=2) and Grade 4 pneumonitis (n=1). There have been 3 deaths during follow-up ranging from 14 to 38 months (median, 28 months). CONCLUSIONS: The MTD of the RT was 74 Gy with weekly carboplatin and paclitaxel. The Phase II portion of this trial is currently under way. The goal is to improve local control and survival with higher doses of RT delivered with this combined modality approach.

The outcome of combined-modality therapy for stage III non-small-cell lung cancer in the elderly.

PURPOSE: The North Central Cancer Treatment Group performed a phase III trial to determine whether chemotherapy plus either bid radiation therapy (RT) or daily (qd) RT resulted in a better outcome for patients with stage III non-small-cell lung cancer (NSCLC). No difference in survival was identified between the two arms. This secondary analysis was performed to examine the relationship between patient age and outcome. PATIENTS AND METHODS: Two hundred forty-six patients were randomized to receive etoposide plus cisplatin and either RT qd or split-course RT bid. This retrospective study compared the outcomes of patients aged >/=70 years ("elderly patients") with those of younger individuals. Of the 244 assessable patients, 63 (26%) were elderly, and 181 (74%) were younger individuals. RESULTS: The 2-year and 5-year survival rates were 39% and 18%, respectively, in patients younger than 70 years, compared with 36% and 13%, respectively, in elderly patients (P =.4). Grade 4+ toxicity occurred in 62% of patients younger than 70 years compared with 81% of elderly patients (P =.007). Grade 4+ hematologic toxicity occurred in 56% of patients younger than 70 years, compared with 78% of elderly patients (P =.003). Grade 4+ pneumonitis occurred in 1% of those younger than 70 years, compared with 6% of elderly patients (P =.02). CONCLUSION: Toxicity, especially myelosuppression and pneumonitis, was more pronounced in the elderly patients receiving combined-modality therapy for locally advanced NSCLC. Despite increased toxicity, elderly patients have survival rates equivalent to younger individuals. Therefore, fit, elderly patients with locally advanced NSCLC should be encouraged to receive combined-modality therapy, preferably on clinical trials with cautious, judicious monitoring. Future studies should explore ways to decrease toxicity of therapy in elderly patients.

Phase III trial comparing chemotherapy plus once-daily or twice-daily radiotherapy in Stage III non-small-cell lung cancer.

PURPOSE: This Phase III study was performed to determine whether chemotherapy plus b.i.d. or q.d. radiotherapy (RT) resulted in superior survival for patients with Stage III non-small-cell lung cancer (NSCLC). METHODS AND MATERIALS: Patients with Stage III NSCLC and an Eastern Cooperative Oncology Group performance status of

The value of combined-modality therapy in elderly patients with stage III nonsmall cell lung cancer.

BACKGROUND: The objective of this study was to assess the value of combined-modality therapy in elderly patients by comparing the differences in outcome between patients who received radiotherapy (RT) alone and patients who received RT plus chemotherapy for stage III nonsmall cell lung cancer (NSCLC). METHODS: The North Central Cancer Treatment Group performed 2 recent Phase III trials for stage III NSCLC. The first trial, NCCTG 90-24-51, included 3 arms: once-daily RT (QDRT) alone, twice-daily RT (BIDRT) alone, and concurrent chemotherapy plus BIDRT. The second trial, NCCTG 94-24-52, included 2 arms and compared concurrent chemotherapy with either QDRT or BIDRT. The chemotherapy arms of both trials included etoposide and cisplatin administered concurrently with RT. Only the patients aged >/=65 years (elderly) who participated in those trials were included in this analysis. RESULTS: Of the 166 elderly patients who were included in this analysis, 37 patients received RT alone, and 129 patients received concurrent chemotherapy plus RT. The median and 5-year survival rates were 10.5 months and 5.4% for the RT alone group compared with 13.7 months and 14.7% for the RT plus chemotherapy group (log-rank P = .05). Patients who received RT plus chemotherapy experienced significantly greater severe toxicity (grade >/=3) compared with patients who received RT alone (89.9% vs 32.4%; P < 0.01). CONCLUSIONS: Elderly patients who participated in these trials appeared to gain a survival advantage from RT and chemotherapy compared with RT alone. As is the case with younger patients, this benefit came at the cost of additional toxicity.

Results of combined-modality therapy for limited-stage small cell lung carcinoma in the elderly.

BACKGROUND: A Phase III trial was conducted by the North Central Cancer Treatment Group to determine whether chemotherapy (etoposide and cisplatin) plus either twice-daily radiotherapy (BIDRT) or once-daily radiotherapy (QDRT) resulted in a better outcome for patients with limited-stage small cell lung carcinoma (LD-SCLC). No difference in survival was identified between the two arms. The current analysis examined the relation between age and outcome for patients treated during this trial. METHODS: The current study included 263 patients with LD-SCLC and an Eastern Cooperative Oncology Group performance status of < or = 2 who were randomized to receive QDRT or split-course BIDRT. The outcomes of the 209 (79%) younger patients (age < 70 years old) were compared with the 54 (21%) elderly patients (age > or = 70 years old). RESULTS: Elderly patients presented with significantly greater weight loss and poorer performance status. The 2-year and 5-year survival rates were 48% and 22% for younger patients compared with 33% and 17% for older patients (P = 0.14). One specific toxicity (i.e., Grade > or = 4 pneumonitis [according to National Cancer Institute Common Toxicity Criteria]) occurred in 0% of those patients age < 70 years compared with 6% of older patients (P = 0.008). Grade 5 toxicity occurred in 1 of 209 (0.5%) patients age < 70 years compared with 3 of 54 (5.6%) older patients (P = 0.03). CONCLUSIONS: Despite having more weight loss, poorer performance status, increased pulmonary toxicity, and more deaths due to treatment, survival was not found to be significantly worse in older individuals. Fit elderly patients with LD-SCLC can receive combined-modality therapy with the expectation of relatively favorable long-term survival. Future research should focus on ways to decrease toxicity especially in the elderly.

Smoking behavior of 226 patients with diagnosis of stage IIIA/IIIB non-small cell lung cancer.

There is limited research of smoking cessation following diagnosis of lung cancer. This prospective study assessed cigarette smoking behavior among 226 patients (142 males, 84 females) prior to, at the time of, and after the diagnosis of unresectable stage IIIA/IIIB non-small cell lung cancer and entry into a phase III trial examining combined thoracic radiation therapy and chemotherapy. Their mean +/-S.D. age was 62.7+/-9.4 years and 95.6% were Caucasian. Of 215 patients with a history of cigarette smoking, 69% (148/215) stopped smoking prior to entry in the trial, 9% (20/215) stopped smoking at some point during the course of the trial, 11% (24/215) continued smoking throughout the trial, 7% (16/215) were smoking at baseline but did not report subsequent smoking status, and smoking status at study entry was missing for the remaining patients. The majority of lung cancer patients were able to stop smoking. A notable subset of patients continued smoking despite diagnosis of lung cancer, enrollment in a clinical trial, treatment-related toxicity, and encouragement from clinicians to stop smoking. Smoking cessation interventions are needed for lung cancer patients who continue to smoke.