Effects of concomitant cisplatin and radiotherapy on inoperable non-small-cell lung cancer.

Schaake-Koning C,et al     N Engl J Med 1992 Feb 20;326(8):524-530  We randomly assigned 331 patients with nonmetastatic inoperable non-small-cell lung cancer to one of three treatments: radiotherapy for two weeks (3 Gy given 10 times, in five fractions a week), followed by a three-week rest period and then radiotherapy for two more weeks (2.5 Gy given 10 times, five fractions a week); radiotherapy on the same schedule, combined with 30 mg of cisplatin per square meter of body-surface area, given on the first day of each treatment week; or radiotherapy on the same schedule, combined with 6 mg of cisplatin per square meter, given daily before radiotherapy. RESULTS. Survival was significantly improved in the radiotherapy-daily-cisplatin group as compared with the radiotherapy group (P = 0.009): survival in the radiotherapy-daily-cisplatin group was 54 percent at one year, 26 percent at two years, and 16 percent at three years, as compared with 46 percent, 13 percent, and 2 percent, respectively, in the radiotherapy group. Survival in the radiotherapy-weekly-cisplatin group was intermediate (44 percent, 19 percent, and 13 percent) and not significantly different from survival in either of the other two groups.  

A randomized trial of induction chemotherapy plus high-dose radiation versus radiation alone in stage III non-small-cell lung cancer.

Dillman RO, et al. N Engl J Med 1990 Oct 4;323(14):940-945    All the patients had documented non-small-cell cancer of the lung with Stage III disease established by clinical or surgical staging.  Patients randomly assigned to group 1 received cisplatin (100 mg per square meter of body-surface area given intravenously on days 1 and 29) and vinblastine (5 mg per square meter given intravenously on days 1, 8, 15, 22, and 29) and then began radiation therapy on day 50 (60 Gy over a 6-week period). Patients assigned to group 2 received the same radiation therapy but began it immediately and received no chemotherapy. RESULTS. The median survival was greater for those in group 1 - 13.8 versus   9.7 months (P = 0.0066 by log-rank test). Rates of survival in group 1 were 55 percent after one year, 26 percent after two years, and 23 percent after three years, as compared with 40, 13, and 11 percent, respectively, in group 2.

Radiotherapy alone versus combined chemotherapy and radiotherapy in nonresectable non-small-cell lung cancer: first analysis of a randomized trial in 353 patients.

Le Chevalier T, et al.   J Natl Cancer Inst 1991 Mar 20;83(6):417-423 We report the results observed in a large, randomized study that compared the effects of radiotherapy alone (the standard therapy) with those of a combination of radiotherapy and chemotherapy in nonresectable squamous cell and large-cell lung carcinoma. The radiation dose was 65 Gy in each group, and chemotherapy included vindesine, cyclophosphamide, cisplatin, and lomustine. In this study, 177 patients received radiotherapy alone (group A), and 176 patients received the combined treatment (group B). The 2-year survival rate was 14% in group A and 21% in group B (P = .08). The distant metastasis rate was significantly lower in group B (P less than .001). Local control was poor in both groups (17% and 15%, respectively) and remained the major problem.

Phase III trial of thoracic irradiation with or without cisplatin for locally advanced unresectable non-small-cell lung cancer: a Hoosier Oncology Group protocol.

Blanke C, et al.  J Clin Oncol 1995 Jun;13(6):1425-1429  Two hundred forty patients with biopsy-proven unresectable NSCLC without distant metastases or lower-stage medically inoperable patients were randomized to one of two treatment arms. Arm A consisted of thoracic XRT alone, 60 to 65 Gy total tumor dose in daily fractions of 1.80 to 2.00 Gy; and arm B consisted of identical XRT with the addition of cisplatin 70 mg/m2 every 3 weeks for three cycles beginning on the first day of irradiation. RESULTS: The overall response rate was 50% on the combination arm versus 38% on the XRT-alone arm (P = .076). The median progression-free survival time was 23 versus 22 weeks, respectively (P = .0537). The median survival time was 43 weeks on the combination arm versus 46 weeks on the XRT arm (Poverall = .3469). The 1-, 2-, and 5-year survival rates were 43%, 18%, and 5% on the combination arm versus 45% 13%, and 2% on the XRT arm, respectively.

Concurrent chemoradiation therapy with oral etoposide and cisplatin for locally advanced inoperable non-small-cell lung cancer: radiation therapy oncology group protocol 91-06.

Lee JS, et al.J Clin Oncol 1996 Apr;14(4):1055-1064. Seventy-nine patients with inoperable NSCLC were enrolled onto a multicenter phase II trial of concurrent chemoradiation therapy. Treatment consisted of two cycles of oral etoposide 100 mg/d (50 mg/d if body-surface area [BSA] < 1.70 m2), intravenous cisplatin 50 mg/m2 on days 1 and 8, and hyperfractionated radiation therapy 5 days per week (1.2 Gy twice daily > 6 hours apart; total 69.6 Gy). RESULTS: After a minimum follow-up duration of 21 months, the 1- and 2-year survival rates and the median survival duration were 67%, 35%, and 18.9 months overall.

Concurrent hyperfractionated irradiation and chemotherapy for unresectable nonsmall cell lung cancer. Results of Radiation Therapy Oncology Group 90-15.

Byhardt RW et al,  Cancer 1995 May 1;75(9):2337-2344.    Vinblastine (5 mg/M2 weekly x 5 weeks) and cisplatin (75 mg/M2 days 1, 29, and 50) were given during twice-daily irradiation (1.2 Gy, 6 hours apart) to 69.6 Gy in 58 fractions in 6 weeks.  RESULTS.  Median survival time was 12.2 months, with an overall 1-year survival of 54%, an estimated 2 year survival of 28% and a 1-year progression free survival of 38%.

Chemotherapy plus radiotherapy compared with radiotherapy alone in the treatment of locally advanced, unresectable, non-small-cell lung cancer. A meta-analysis.

Pritchard RS, Ann Intern Med 1996 Nov 1;125(9):723-9 Fourteen articles reporting on a total of 2589 patients were reviewed. Compared with radiotherapy, the combination of Chemotherapy and radiotherapy reduced the risk for death at 1 year (relative risk, 0.88), 2 years (relative risk, 0.87), and 3 years (relative risk, 0.83). This corresponded to a mean gain in life expectancy of about 2 months. The magnitude of the treatment effect Was similar when trials of concurrently and sequentially administered chemotherapy were considered separately.

Radiosensitization with carboplatin for patients with unresectable stage III non-small-cell lung cancer: a phase III trial of the Cancer and Leukemia Group B and the Eastern Cooperative Oncology Group.

Clamon University of Iowa J Clin Oncol 1999 Jan;17(1):4-11 Two hundred eighty-three patients with inoperable stage III non-small-cell lung cancer were entered onto a randomized trial by the Cancer and Leukemia Group B and the Eastern Cooperative Oncology Group. Randomization was performed before initiation of any therapy. All patients received an induction chemotherapy program with vinblastine and cisplatin for 5 weeks, followed by 6,000 cGy of radiation therapy over 6 weeks. One hundred thirty-seven patients were randomized to this therapy regimen alone; 146 patients were randomized to receive carboplatin at 100 mg/m2/wk concurrent with the radiation therapy. RESULTS: The complete response was 18% with concurrent carboplatin versus 10% with radiotherapy alone (P = .101). There was no difference with respect to failure-free survival (10% with carboplatin and 9% with radiotherapy alone) or overall survival (13% with carboplatin and 10% with radiotherapy alone) at 4 years. In patients not receiving carboplatin, the relapse rate was 69% within the field of radiation and 53% in the boost volume. In patients receiving carboplatin, the relapse rate was 59% within the field of radiation and 43% in the boost volume. Patients with cancers more than 70 cm2 in size had significantly poorer survival (P = .01). CONCLUSION: Carboplatin at the dose and schedule used did not significantly impact on disease control or survival. The relapse rate within the chest remained more than 50%. More effective regimens will be required to impact on local disease control and survival.

Single-agent paclitaxel and radiation for non-small cell lung cancer.

Akerley. Rhode Island Hospital, Semin Radiat Oncol 1999 Apr;9(2 Suppl 1):85-9 In the phase II trial in patients with inoperable stage IIIA or stage IIIB NSCLC, paclitaxel 60 mg/m2/wk (for 6 weeks) plus radiation therapy (60 Gy) resulted in an overall response rate of 86%. The overall median survival was 20 months, and projected 1-, 2-, and 3-year survival rates were 60%, 54%, and 39%, respectively.

Multiinstitutional phase II trial of paclitaxel, carboplatin, and concurrent radiation therapy for locally advanced non-small-cell lung cancer.

Choy. Vanderbilt University J Clin Oncol 1998 Oct;16(10):3316-22 On an outpatient basis for 7 weeks, patients received paclitaxel 50 mg/m2 weekly over 1 hour; carboplatin at (area under the curve) AUC 2 weekly; and radiation therapy of 66 Gy in 33 fractions. After chemoradiation therapy, patients received an additional two cycles of paclitaxel 200 mg/m2 over 3 hours and carboplatin at AUC 6 every 3 weeks. RESULTS: Thirty-nine patients were eligible for the study. The survival rates at 12 months were 56.3%, and at 24 months, 38.3%, with a median overall survival of 20.5 months. The progression-free survival rates at 12 months were 43.6%, and at 24 months, 34.7%, with a median progression-free survival of 9.0 months. The overall response rate (partial plus complete response) of 37 assessable patients was 75.7%.