Gemcitabine plus etoposide in chemonaive extensive disease small-cell lung?cancer: A multi-centre phase II study

Background:Both gemcitabine and etoposide are active in thetreatment of small-cell lung cancer (SCLC), and are characterised bymild toxicity profiles. The combination of both drugs was found to befeasible and active in a phase I dose-finding study in solid tumours.Therefore, a phase II trial was initiated to examine the activity andtoxicity of this schedule in extensive disease SCLC. Patients and methods:Forty-two chemo-naïve extensivedisease SCLC patients were enrolled to receive gemcitabine 1000mg/m², days 1, 8 and 15, and etoposide 80 mg/m²,days 8, 9 and 10 of a 28-day cycle. Results:Thirty-seven patients were evaluable for efficacy(five received less than one cycle). No complete responses wereobserved, but partial responses were seen in 17 patients, yielding anoverall response rate of 46%. The median duration of response was5.8 months. Disease stabilisation was obtained in another 10patients (27%). The median survival of the 37 protocol-qualifiedpatients was 10.5 months (95% confidence interval (CI):7.5–12.0). The levels of WHO grade 3 and 4 toxicities were low andclinically manageable. Conclusion:In comparison with standard platinum-basedregimens, this combination of gemcitabine and etoposide resulted in asomewhat lower response rate, but a similar median survival time.Haematological toxicity was more pronounced than expected from thetoxicity data of each agent individually. However, because of its mildnon-haematological toxicity, and its ability to be administered inan outpatient setting, this combination provides a reasonable palliativeoption for patients with extensive disease SCLC.     

A phase I and pharmacologic study of capecitabine and paclitaxel in?breast?cancer patients

Background:Based on preclinical studies demonstrating that treatment with paclitaxel upregulates intratumoral thymidine phosphorylase (dTHdPase), which catalyzes the final step in the conversion of the oral fluoropyrimidine capecitabine to 5-fluorouracil (5-FU), as well as the overlapping spectra of activity for these agents, particularly in metastatic breast cancer, this phase I study evaluated the feasibility of administering capecitabine on an intermittent schedule in combination with paclitaxel in previously-treated patients with locally advanced or metastatic breast cancer. The study also sought to recommend doses for subsequent disease-specific studies, identify clinically significant pharmacokinetic interactions, and detect preliminary antitumor activity. Patients and methods:Nineteen previously treated women with metastatic breast cancer whose prior treatment included neither paclitaxel or capecitabine received one hundred one courses of capecitabine and paclitaxel. Paclitaxel was administered as a three-hour intravenous (i.v.) infusion at a fixed dose of 175 mg/m² and capecitabine was administered as 2 divided daily doses for 14 days followed by a seven-day rest period every 3 weeks. The dose of capecitabine was increased from a starting dose of 1650 mg/m²/d. The plasma sampling scheme in the first course permitted characterization of the pharmacokinetics of each agent given alone and concurrently to detect major pharmacokinetic interactions. Results:Palmar–plantar erythrodysesthesia (hand–foot syndrome) and neutropenia were the principal dose-limiting toxicities (DLT). Other toxicities included diarrhea and transient hyperbilirubinemia. Three of eight new patients treated with capecitabine 2000 mg/m²/d and paclitaxel 175 mg/m² experienced DLT in the first course, whereas none of eleven new patients treated with capecitabine 1650 mg/m²/d and paclitaxel 175 mg/m² developed DLT. Pharmacokinetic studies indicated that capecitabine did not grossly affect the pharmacokinetics of paclitaxel, and there were no major effects of paclitaxel on the pharmacokinetics of capecitabine and capecitabine metabolites. However, AUC values for the major 5-FU catabolite, fluoro-beta-alanine (FBAL), were significantly lower in the presence of paclitaxel. Two complete and seven partial responses (56% response rate) were observed in sixteen patients with measurable disease; four of six patients whose disease was previously treated with high-dose chemotherapy and hematopoietic stem-cell support had major responses. Seven of nineteen patients had stable disease as their best response. Conclusions:Recommended combination doses of capecitabine on an intermittent schedule and paclitaxel are capecitabine 1650 mg/m²/d orally for 14 days and paclitaxel 175 mg/m² i.v. every 3 weeks. The favorable preclinical interactions between capecitabine and paclitaxel, as well as the acceptable toxicity profile and antitumor activity in patients with metastatic breast cancer, support further clinical evaluations to determine an optimal role for the combination of capecitabine and paclitaxel in breast cancer and other relevant malignancies.     

Α multicenter phase II study of pegylated liposomal doxorubicin in combination with irinotecan as second-line treatment of patients with refractory small-cell lung cancer

Purpose  

To evaluate efficacy and toxicity of a combination of pegylated liposomal doxorubicin and irinotecan in patients with refractory small-cell lung cancer.     

Randomized phase II–III study of bevacizumab in combination with chemotherapy in previously untreated extensive small-cell lung cancer: results from the IFCT-0802 trial

IFCT study administering 7.5 mg/kg Bevacizumab plus chemotherapy after chemotherapy induction did not improve outcomes in extensive SCLC patients.BackgroundThis randomized phase II–III trial sought to evaluate the efficacy and safety of adding bevacizumab (Bev) following induction chemotherapy (CT) in extensive small-cell lung cancer (SCLC).Patients and methodsEnrolled SCLC patients received two induction cycles of CT. Responders were randomly assigned 1:1 to receive four additional cycles of CT alone or CT plus Bev (7.5 mg/kg), followed by single-agent Bev until progression or unacceptable toxicity. The primary end point was the percentage of patients for whom disease remained controlled (still in response) at the fourth cycle.ResultsIn total, 147 patients were enrolled. Partial response was observed in 103 patients, 74 of whom were eligible for Bev and randomly assigned to the CT alone group (n = 37) or the CT plus Bev group (n = 37). Response assessment at the end of the fourth cycle showed that disease control did not differ between the two groups (89.2% versus 91.9% of patients remaining responders in CT alone versus CT plus Bev, respectively; Fisher's exact test: P = 1.00). Progression-free survival (PFS) since randomization did not significantly differ, with a median PFS of 5.5 months [95% confidence interval (CI) 4.9% to 6.0%] versus 5.3 months (95% CI 4.8% to 5.8%) in the CT alone and CT plus Bev groups, respectively [hazard ratio (HR) for CT alone: 1.1; 95% CI 0.7% to 1.7%; unadjusted P = 0.82]. Grade ≥2 hypertension and grade ≥3 thrombotic events were observed in 40% and 11% of patients, respectively, in the CT plus Bev group. Serum vascular endothelial growth factor (VEGF) and soluble VEGF receptor titrations failed to identify predictive biomarkers.ConclusionAdministering 7.5 mg/kg Bev after induction did not improve outcome in extensive SCLC patients.     

Serum p53 antibodies: predictors of survival in small-cell lung cancer?

Serum p53 antibodies have been shown to be a poor prognostic marker in resected non-small-cell lung cancer (NSCLC), but studies in small-cell lung cancer (SCLC) have been contradictory. We have studied the incidence of p53 antibodies in a large SCLC cohort treated at one oncology centre and correlated the results with survival. 231 patients (63% male, median age 65), diagnosed and treated for SCLC between 1987 and 1994 at The Royal Marsden Hospital NHS Trust, had sera stored pretreatment. All samples were tested for p53 antibodies (p53-Ab) using a standardized ELISA technique with a selection of strongly ELISA positive, weakly ELISA positive and negative samples being confirmed with immunoprecipitation. 54 patients were positive for p53-Ab (23%). The presence of a high titre of p53-Ab (titre ratio >5) appears to be associated with a survival advantage with a relative risk of death of 1.71 (95% CI: 1.14-2.58) in those without the antibody (P = 0.02). This study, the largest homogeneous group so far looking at p53-Ab in SCLC, suggests that p53 antibody detection may have a role in predicting outcome in this type of cancer.     

Alternating radiotherapy and chemotherapy for inoperable stage III non–small-cell lung cancer: long-term results of two phase II GOTHA trials

Purpose/Objective: To report on two consecutive Phase II cooperative trials in which we evaluated the combination of alternating hyperfractionated accelerated radiotherapy and cisplatin-based chemotherapy in inoperable Stage III non-small cell lung cancer (NSCLC).Patients & Methods: Between February 1986 and September 1989, 65 patients were entered in the first trial (GOTHA I), and between December 1989 and October 1992 67 were enrolled in the second trial (GOTHA II). In both protocols, radiotherapy (RT) was administered twice daily, at 6 h intervals, 5 days a week, to a total dose of 63 Gy in 42 fractions of 1.5 Gy. RT was given during weeks 2, 3, 6, and 7, over an elapsed time of 6 weeks. In GOTHA I, three cycles of cisplatin, 60 mg/m² day 1, mitomycin, 8 mg/m² day 1, and vindesin 3 mg/m² day 1 and the first day of the following week, were given during weeks 1, 5, and 9; in GOTHA II, cisplatin 70 mg/m² day 1 and vinblastin 5 mg/m² day 1 and the first day of the following week were given during weeks 1, 5, 9, 13, 17, and 21.Results: With a minimum follow-up of 3 years, the 1-, 2-, 5-, and 8-year overall survival probability was 56% (95% CI 47–64%), 27% (20–35%), 12% (7–18%) and 9% (3–16%), respectively, with a median survival of 13.6 months (11.4–16.8). Median follow-up for survivors was 6 years (3.3–9.9). There were no survival differences between Stages IIIA and IIIB (p = 0.84), performance status 0, 1, 2 (p = 0.87), sex (p = 0.45) or between the two treatment protocols. At this time, 14 patients are alive, and 118 have died: 102 from NSCLC, 4 from acute toxicity, 2 from secondary surgery, 4 from other medical causes, and 6 from unknown causes. Correlation between response and long-term survival was poor, since of the 24 patients who survived 3 years or more, only 6 (25%) were classified as having a complete response; the remainder having either a partial response (11, 46%), no change (6, 25%), or “progressive disease” (1, 4%). First site of relapse was local in 31% of these cases, distant in 43%, local and distant in 15%, and unknown in 11%. Main grade 3–4 acute toxicities were nausea-vomiting (17%), mucositis (15%), leukopenia (41%), and thrombocytopenia (11%). Eight patients presented with grade 3–4 symptomatic lung radiation pneumopathy.Conclusion: Based on this experience with 132 patients, this combination of alternated RT and chemotherapy (CT) for inoperable Stage III NSCLC is feasible with acceptable toxicity, and long-term results suggest a gain in survival when compared to those obtained with conventional RT alone. However, the still high local and distant failure rates indicate that both local and systemic therapies need to be improved.     

A multicenter randomized phase II study of oral vs. intravenous vinorelbine in?advanced non-small-cell lung cancer patients

Purpose:A randomized phase II trial of oral vs. intravenous(i.v.) vinorelbine was designed to determine the efficacy and safety oforal vinorelbine with an intrapatient dose escalation in previouslyuntreated patients with advanced non-small-cell lung cancer (NSCLC). Patients and methods:Between December 1997 and April 1999,115 patients with stage IIIB or IV NSCLC were randomized (2 to 1) toreceive either oral vinorelbine at a dose of 60 mg/m²/weekfor the first three administrations and then increased to 80mg/m²/week in the absence of severe neutropenia, or i.v.vinorelbine at 30 mg/m²/week. Results:Onehundred and fourteen patients (76 in the oral arm and 38 in the i.v.arm) were treated. Ninety-eight patients (86%) were eligible andassessable. The two treatment arms were well-balanced for demographicand prognostic features. After external panel review, the response ratesin evaluable patients were 14% in the oral arm and 12% inthe i.v. arm. The median progression-free survival with oral and i.v.vinorelbine was 3.2 months and 2.1 months, respectively, and the mediansurvival – 9.3 and 7.9 months, respectively. The most commonhematological toxicity was neutropenia, which was severe (grade3–4) in 46% of patients and for 7% ofadministrations in the oral arm, and in 62% of patients and for25% of administrations in the i.v. arm. Non-hematologicaltoxicities including nausea, vomiting, anorexia, weight loss, diarrheaand constipation were generally mild to moderate. Conclusion:The activity of oral and i.v. vinorelbine in advanced NSCLC appearsto be comparable. The safety profiles of both formulations lookqualitatively similar. Oral vinorelbine can therefore be considered agood alternative to i.v. administration.     

A phase I trial of carboplatin and etoposide for elderly (≥75 year-old) patients with small-cell lung cancer

Purpose: The combination of carboplatin and etoposide is currently considered the most appropriate regimen for treating elderly patients with small-cell lung cancer (SCLC). Previous reports on elderly patients, 70 years or older, found that the recommended dose was close to that of younger patients. Then, we conducted a phase I study of carboplatin and etoposide in elderly patients, 75 years or older, with SCLC. This study aimed to determine the maximum tolerated dose (MTD) and dose-limiting toxicity (DLT). Methods: Twenty-six patients fulfilling the eligibility criteria, chemotherapy-naive, performance status (PS) of 0–2, age ≥75, and adequate organ functions were enrolled. Patients’ characteristics were: male/female=21/5; PS 0/1/2=9/11/6; median age (range)=78 (75–82); and limited/extensive stage=16/10. The patients intravenously received carboplatin with a target AUC of 4 or 5 mg min/ml (Chatelut formula) on day 1 and etoposide at 80–120 mg/m² on days 1, 2 and 3. Therapy was repeated four times in every 4 weeks. Results: The MTD of carboplatin/etoposide was AUC=5/80, 4/110, and 4/120. The DLTs were thrombocytopenia, neutropenia, leukopenia, and febrile neutropenia. Overall, grade 4 thrombocytopenia, neutropenia (≥4 days), leukopenia (≥4 days), and febrile neutropenia occurred in 27, 20, 7, and 13% of cases at MTD levels, respectively, and 0% at other levels. Twenty of 26 patients showed objective responses (2CR, 18PR; RR=77%). Conclusion: A dose of carboplatin of AUC=4 and etoposide of 100 mg/m² was recommended in this regimen.The authors indicated no potential conflicts of interest.     

Comparing the effectiveness of different EGFR-TKIs in patients with EGFR mutant non–small-cell lung cancer: A retrospective cohort study in Taiwan

The study was to compare the effectiveness of different epidermal growth factor receptor—tyrosine kinase inhibitors (EGFR-TKIs) in patients with advanced non-small-cell lung cancer (NSCLC) and received EGFR-TKIs as first-line therapy. This retrospective cohort study was conducted using data from real-world settings. Patients with stage IIIB and IV NSCLC and first received gefitinib, erlotinib, or afatinib between 2011 and 2015 were included. The date of the first claim for EGFR-TKIs was set as the index date. Study endpoints were all-cause death and treatment failure that was defined when patients added on or switched to chemotherapy or terminal care. A total of 5,940 patients, including 3,982 (67.0%) receiving gefitinib, 1,207 (20.3%) receiving erlotinib, and 751 (12.7%) receiving afatinib, were eligible for this study. The 1-year overall survival (OS) rates for gefitinib, erlotinib, and afatinib groups were 74% (95% confidence interval [CI]: 72–75%), 75% (95% CI: 73–77%), and 80% (95% CI: 77–83%), respectively. Compared to gefitinib, afatinib was associated with a lower risk of all-cause death (adjusted hazard ratio [aHR] = 0.82, 95% CI: 0.72–0.93) but not erlotinib (aHR = 0.95, 95% CI: 0.86–1.05). Similar results were also found regarding the effectiveness of treatment. All the three EGFR-TKIs showed no differences for both outcomes among patients with an Eastern Cooperative Oncology Group Performance Score of 2. The real-world data exhibited afatinib was more likely to be used for younger patients in a better condition than other EGFR inhibitors, and observed prolonged OS and treatment effectiveness compared to gefitinib after performing a multivariate Cox regression analysis.     

Can elective nodal irradiation be omitted in stage III non-small-cell lung cancer? Analysis of recurrences in a phase II study of induction chemotherapy and involved-field radiotherapy

PURPOSE: To establish the recurrence patterns when elective mediastinal irradiation was omitted, patients with Stage III non-small-cell lung cancer were treated with sequential chemotherapy (CHT) and involved-field radiotherapy (RT). METHODS AND MATERIALS: Fifty patients were treated with either two or four cycles of induction CHT, followed by once-daily involved-field RT to 70 Gy, delivered using three-dimensional treatment planning. The contoured gross tumor volume consisted of the pre-CHT tumor volume and nodes with a short-axis diameter of > or = 1 cm. Patients were reevaluated at 3 and 6 months after RT using bronchoscopy and chest CT. Elective nodal failure was defined as recurrence in the regional nodes outside the clinical target volume, in the absence of in-field failure. RESULTS: Of 43 patients who received doses > or = 50 Gy, 35% were disease free at last follow-up; in-field recurrences developed in 27% (of whom 16% had exclusively in-field recurrences); 18% had distant metastases exclusively. No elective nodal failure was observed. The median actuarial overall survival was 18 months (95% confidence interval 14-22) and the median progression-free survival was 12 months (95% confidence interval 6-18). CONCLUSION: Omitting elective mediastinal irradiation did not result in isolated nodal failure. Future studies of concurrent CHT and RT for Stage III non-small-cell lung cancer should use involved-field RT to limit toxicity.     

Single-agent oxaliplatin in pretreated advanced breast cancer patients: A?phase II study

Purpose:Oxaliplatin (L-OHP), a new platinum analogue, is anactive drug in colorectal and ovarian cancer. In this phase II study weexplored tolerability and activity of oxaliplatin as a single agent inmetastatic breast carcinoma patients. Patients and methods:Fourteen anthracycline pretreated advancedbreast cancer patients were enrolled. Oxaliplatin was given at 130mg/m² on day 1 and repeated every three weeks. Analysis oftoxicity, response rate and survival was performed. Results:The median number of courses per patient was four (range2–6). The median administered dose-intensity was 43.3mg/m²/week (range 32.5–43.3) which represents 100% ofprojected dose-intensity. No severe toxicity was encountered. Three patientsdeveloped acute transient laryngeal symptoms. Three patients displayed apartial response (21%), (95% confidence interval (CI):0%–43%), two stable disease (14%) and nineprogressed (64%). Response lasted five, four and five monthsrespectively. Median survival was 12 months. Conclusions:In this limited experience, oxaliplatin appeared tobe well tolerated and moderately active in advanced anthracycline-pretreatedbreast cancer patients. Combination chemotherapy with other active drugs suchas 5-fluorouracil (5-FU), anthracyclines and taxanes should represent the nextstep of development of this new drug.     

A phase Ⅰ study of nimotuzumab plus docetaxel in chemotherapy-refractory/resistant patients with advanced non-small-cell lung cancer

Background

To determine the safety and therapeutic efficacy of nimotuzumab (h-R3) combined with docetaxel in advanced non-small-cell lung cancer (NSCLC) patients who have failed to respond to prior first-line chemotherapy.

Methods

In this single-center, open-label, dose-escalating phase I trial, patients with epidermal growth factor receptor (EGFR)-expressing stage IV NSCLC were treated with nimotuzumab plus docetaxel according to a dose escalation schedule. The safety and efficacy of the combination treatment were observed and analyzed.

Results

There were 12 patients with EGFR-expressing stage IV NSCLC enrolled. The dose of nimotuzumab was escalated from 200 to 600 mg/week. The longest administration of study drug was 40 weeks at the 600 mg/week dose level. Grade III–IV toxicities included neutropenia and fatigue, and other toxicities included rash. Dose-limiting toxicity occurred with Grade 3 fatigue at the 200 mg dose level of nimotuzumab and Grade 4 neutropenia with pneumonia at the 600 mg dose level of nimotuzumab. No objective responses were observed, and stable disease was observed in eight patients (66.7%). The median progression-free survival (PFS) was 4.4 months in all patients, 1.3 months in patients with the EGFR mutation, and 4.4 months in those with wild type EGFR (EGFR WT). The median survival time (MST) was 21.1 months in all patients, 21.1 months in patients with EGFR mutation, and 26.4 months in patients with EGFR WT.

Conclusions

Nimotuzumab and docetaxel combination therapy was found to be well tolerated and efficacious. Further study of nimotuzumab is warranted in advanced NSCLC patients.     

Phase I and pharmacologic study of weekly gemcitabine and paclitaxel in chemo-na?ve patients with advanced non-small-cell lung cancer

Background:Gemcitabine (GEM) and paclitaxel (TAX) are active,non-cross-resistant drugs in non-small-cell lung cancer (NSCLC). We performeda phase I study to determine the maximum-tolerated dose (MTD), antitumoractivity and pharmacokinetics of GEM and TAX given weekly in chemo-naïvepatients with advanced NSCLC. Patients and methods:Escalating doses of GEM (800–2000mg/m²) and TAX (60–100 mg/m²) were administeredon days 1, 8, 15 every 4 weeks to 35 patients with advanced NSCLC. Plasmapharmacokinetics of TAX and GEM was assessed at the three higher dose-levels. Results:Dose-escalation was discontinued in absence of MTDbecause of increased cumulative toxicity leading to dose modification ortreatment delay at levels 6 and 7 (TAX 100 mg/m² plus GEM 1750 and,respectively, 2000 mg/m²). Hematological toxicity included grade4 neutropenia in 3% of cycles, grade 3 thrombocytopenia in one cycleand febrile neutropenia in three cycles. Maximal non-hemathological toxicitywas grade 3 elevation in serum transaminases and grade 2 neuro-sensorytoxicity in 8% and 5% of cycles, respectively. At the two higherdose-levels a non-linear pharmacokinetics of GEM was observed with aremarkable variability of C_max and AUC. No pharmacokineticinteractions were reported. Objectives responses were seen at all dose levels,with an overall response rate of 43% (95% confidence interval(95% CI): 25.5%–62.6%) in 30 evaluable patients. Conclusions:The weekly administration of GEM and TAX is very welltolerated, and has shown promising antitumor activity in NSCLC. In view of thecumulative toxicity and of the pharmacokinetic profile of GEM, doses of 1500mg/m² of GEM and 100 mg/m² of TAX are recommended forphase II studies.     

Phase II trial of paclitaxel and carboplatin in metastatic small-cell lung cancer: a Groupe Fran?ais de Pneumo-Cancérologie study.

PURPOSE: To evaluate the efficacy and safety of paclitaxel and carboplatin in the treatment of previously untreated patients with metastatic small-cell lung cancer (SCLC). PATIENTS AND METHODS: Eligible patients were aged 18 to 75 years with an Eastern Cooperative Oncology Group (ECOG) score < or = 2 and life expectancy > or = 12 weeks. Paclitaxel (200 mg/m(2)) was infused over 3 hours, before carboplatin (area under the curve [AUC] 6; Calvert formula) infused over 1 hour, once every 3 weeks for six cycles maximum. Prednisolone, dexchlorpheniramine, and ranitidine were standard premedication. Response to treatment was assessed every two cycles, and nonresponding patients were withdrawn from the trial to receive standard chemotherapy. RESULTS: Of the 50 patients entering the study, 48 and 46 patients were assessable for toxicity and response, respectively. The overall response rate was 65%, with complete responses in three patients. Five patients had stable disease (11%) and 11 patients experienced progressive disease (24%). Median survival was 38 weeks, and median duration of response was 20 weeks. One-year survival was 22.5%. For a total of 232 cycles, grade 3 and 4 toxicity was 33% for neutropenia, 3.5% for thrombocytopenia, and 4% for anemia. Four patients had neutropenic fever (one toxic death). Nonhematologic toxicity was mainly grade 1 and 2 paresthesia (21% of patients); grade 3 myalgia/arthralgia was observed in 6.5% of patients. CONCLUSION: First-line chemotherapy with paclitaxel and carboplatin in metastatic SCLC achieved a response rate and survival similar to standard regimens. With 1-day administration and a tolerable toxicity profile, this combination merits further investigation.     

Randomized phase III trial of prophylactic cranial irradiation versus observation in patients with fully resected stage IIIA–N2 nonsmall-cell lung cancer and high risk of cerebral metastases after adjuvant chemotherapy

This prospective, randomized, phase III trial shows that prophylactic cranial irradiation prolongs disease-free survival, decreases the rate of cerebral metastases and does not affect quality-of-life for patients with fully resected postoperative pathologically confirmed stage IIIA-N2 non-small-cell lung cancer and high risk of cerebral metastases after adjuvant chemotherapy.BackgroundThis study compared prophylactic cranial irradiation (PCI) with observation in patients with resected stage IIIA–N2 non-small-cell lung cancer (NSCLC) and high risk of cerebral metastases after adjuvant chemotherapy.Patients and methodsIn this open-label, randomized, phase III trial, patients with fully resected postoperative pathologically confirmed stage IIIA–N2 NSCLC and high cerebral metastases risk without recurrence after postoperative adjuvant chemotherapy were randomly assigned to receive PCI (30 Gy in 10 fractions) or observation. The primary end point was disease-free survival (DFS). The secondary end points included the incidence of brain metastases, overall survival (OS), toxicity and quality of life.ResultsThis trial was terminated early after the random assignment of 156 patients (81 to PCI group and 75 to control group). The PCI group had significantly lengthened DFS compared with the control group, with a median DFS of 28.5 months versus 21.2 months [hazard ratio (HR), 0.67; 95% confidence interval (CI) 0.46–0.98;P = 0.037]. PCI was associated with a decrease in risk of brain metastases (the actuarial 5-year brain metastases rate, 20.3% versus 49.9%; HR, 0.28; 95% CI 0.14–0.57;P < 0.001). The median OS was 31.2 months in the PCI group and 27.4 months in the control group (HR, 0.81; 95% CI 0.56–1.16;P = 0.310). While main toxicities were headache, nausea/vomiting and fatigue in the PCI group, they were generally mild.ConclusionIn patients with fully resected postoperative pathologically confirmed stage IIIA–N2 NSCLC and high risk of cerebral metastases after adjuvant chemotherapy, PCI prolongs DFS and decreases the incidence of brain metastases.