Unresectable NSCLC Research Articles

Adenosine triphosphate-based chemotherapy response assay (ATP-CRA)-guided cisplatin-based two-drug chemotherapy in unresectable non-small cell lung cancer

7118 Background: Heterogeneity of tumor response to chemotherapy is a big obstacle in cancer treatment. The aim of this study was to investigate correlations of ATP-CRA and clinical outcome after ATP-TCA-guided cisplatin-based chemotherapy in unresectable NSCLC. Methods: From Sep. 2003 to Oct. 2005, ATP-CRA was done in tumor tissue specimen obtained from patients with suspected lung malignancy. ATP-CRA tested sensitivities of anticancer drugs used widely in advanced NSCLC such as cisplatin, carboplatin, paclitaxel, docetaxel, gemcitabin, and vinorelbine. The cell death rate was determined by measuring the intracellular ATP levels of untreated controls and drug exposed cells. A sensitive drug was defined as a drug producing 30% or more reduction of ATP compared to untreated controls. Test-guided cisplatin-based two-drug chemotherapy was given to pathologically confirmed NSCLC. Results: 31 patients were enrolled and their median follow-up duration was 13.3 months. Response rate was 48.3%. Median progression-free and overall survivals were 4.4 months and 11.2 months, respectively. Patients were dichotomized into platinum-sensitive (S) and resistant (R) groups. S-group (19) contained cases sensitive to platinum alone (6) or both drugs (13). R-group (12) contained cases sensitive to none (9) or the other drug alone (3). Clinical response rate was higher in S-group (75.0% vs 35.3% in R-group; p = 0.0635). Considering correlations of test results and clinical response, positive/negative predictive values were 64.7% / 75.0% with the predictive accuracy of 69.0%. Although without significant differences in histology, stage, and performance status, S-group had longer progression-free (5.0 vs 2.4 months in R-group; p = 0.056) and overall (21.8 vs 9.7 months in R-group; p = 0.018) survivals. Conclusions: In vitro chemosensitivity test, ATP-CRA results and clinical outcome were correlated well after test-guided cisplatin-based two-drug chemotherapy in unresectable NSCLC, presenting favorable response and survival in platinum-sensitive versus resistant group. [Table: see text]

Effect of paclitaxel-carboplatin (PC) consolidation chemotherapy after weekly PC concurrent chemo-radiotherapy (CCR) for patients with locally advanced non-small cell lung cancer (LA-NSCLC): 3-year definitive results of the B001-phase III GERCOR-study

7112 Background: Local control rate of LA-NSCLC seems better after concurrent CCR than after sequential schedule; the role of additional chemotherapy is not clearly defined. A multi-institutional phase-III trial was conducted to evaluate the role of chemotherapy consolidation after CCR Methods: Eligibility criteria included mediastinoscopy-controlled unresectable NSCLC stage IIIA (27%) - IIIB (59%) and inoperable mediastinal recurrence after surgery (14%), PS < 3, clinical target volume compatible with a minimal 60 Gy dose radiation. After registration, patients (pts) were treated with combination of weekly P (45 mg/m2), C (AUC 2), and radiotherapy 60–66 Gy (5 × 2 Gy per week). The pts with response or stable disease were randomized either to receive 3 cycles of P (175 mg/m2) and C (AUC 5) consolidation on days 1–22–43 or observation. Primary endpoint was OS (log-rank test), planned sample was 122 pts. Results: Actually, 71 pts were enrolled. Thirty pts (42%) were not randomized because of progression (22%) and disease-related death (22%), toxicity (26%), refusal (9%), protocol violation (21%). Toxicity grade 3–4 per patient: for the PC-TRT sequence; neutropenia 5%, febrile neutropenia 5%, thrombopenia 5%, pneumonitis 5%, oesophagitis 19%. For the PC consolidation sequence; neutropenia 24%, febrile neutropenia 6%, thrombopenia 0% (no treatment-related death). After a minimal follow-up of 3 years, despite poor inclusion rate, OS and PFS were greater in the PC consolidation group with 3-year OS: 29.9% vs 10% (HR = 0.45; CI 0.95: 0.22–0.91) (p = 0.002) and 3-year PFS: 27.8% vs 10% (HR = 0.6; CI 0.95: 0.3–1.3) (p = 0.17). Nine pts developed metastasis in each treatment arm. Conclusions: The addition of PC consolidation to PC-CCR is not easily feasible for all LA-NSCLC. For selected pts (only 58% of pts in this trial), despite premature ending of the trial because of slow accrual, PC consolidation significantly improved the 3-year OS and probably PFS. Because no difference in the metastatic incidence was observed, the effect of chemotherapy dosage in the consolidation arm could be explained by delaying metastasis. No significant financial relationships to disclose.

Expression and prognostic implications of apoptosis-related proteins in locally unresectable non-small cell lung cancers

Apoptosis related proteins in early staged NSCLC seem to have prognostic value. We studied the value of a combination of eight of those proteins in advanced NSCLC. Bronchoscopically procured tumor biopsies of NSCLC patients were stained immunohistochemically and rated for expression of eight different cellular proteins. Patients were treated with 60 Gy radiotherapy with or without carboplatin as radiosensitizer. Apoptotic proteins in tumors that showed positive staining were the highest for Bax (99%), Fas (92%), FasL (87%), Rb (87%), p21(WAF1) (73%), and p53 (70%), and the lowest for c-myc (58%) and Bcl-2 (58%). In the Cox regression analysis Bcl-2 positivity (RR = 0.61, 95% CI, 0.37-0.98, p = 0.04) was predictive for overall survival. Only Bcl-2 staining percentage (RR(10) (RR associated with an increase in stained cells of 10%) = 0.93, 95% CI, 0.89-0.99), p53 (RR(10) = 0.94, 95% CI, 0.89-0.99) and FasL (RR(10) = 0.92, 95% CI, 0.86-0.99) were predictive for a longer progression-free survival. No specific constellation of apoptotic proteins was associated with tumor response. Bcl-2 expression in tumor tissue of patients with unresectable NSCLC predicts a better overall survival, while Bcl-2, p53, and FasL expressions predict for a longer progression-free survival.

1131 POSTER Addition of CPG 7909 to taxane/platinum regimen for first-line treatment of unresectable NSCLC improves objective response in phase II clinical trial

To retrospectively compare primary treatment with weekly carboplatin/paclitaxel (PC-W) to the standard 3-weekly carboplatin/paclitaxel (PC-3W) in women with advanced epithelial ovarian cancer, tubal carcinoma and primary peritoneal carcinoma.Medical records were assessed for age, stage of disease, tumor histology and grade, BRCA mutation status, and platinum sensitivity. Patients were treated with either paclitaxel (175 mg/m2) and carboplatin (AUC 6) every three weeks (PC-3W; 133 patients), or with weekly paclitaxel (80 mg/m2) and weekly carboplatin (AUC 2) on days 1, 8, and 15 every 28 days (PC-W; 267 patients).Patient baseline characteristics were similar in both groups. Median overall survival (OS) was similar for PC-W and PC-3W (64.5 months vs. 61.5 months), but PC-W had longer median progression-free survival [PFS: 27.4 months (95% CI, 22.7–31.4) vs. 19.5 months (95% CI, 15.6–22.2) for PC-3W, p = 0.0024] and a longer median platinum-free interval [PFI: 22.1 months (95% CI, 16.0–24.5) vs. 14.2 months (95% CI, 10.7–17.2) for PC-3W, p = 0.0075]. PC-W showed a significantly higher response rate (86.4% vs. 77.9% for PC-3W, p = 0.0435). Multivariate analysis including for age at diagnosis, stage of disease, optimal debulking, histology, BRCA status, pretreatment CA-125 and PFI revealed that the PC-W women had lower risk of death (HR = 0.587, 95% CI, 0.402–0.857, p = 0.0058), lower risk of disease progression (HR = 0.494, 95% CI, 0.359–0.680, p < 0.0001), higher 2- and 3-year survival rates, and decreased grade II hair loss, neuropathy and thrombocytopenia compared with the PC-3W women.The PC-W protocol improved PFS and had a similar OS as PC-3W.

PD-114 Mature results of combined high dose 3D conformal radiation (74Gy) and chemotherapy in treatment of inoperable and/or unresectable localized NSCLC. Efficacy, tolerance, relationship with dose and volumes (V20)

PD-114 Mature results of combined high dose 3D conformal radiation (74Gy) and chemotherapy in treatment of inoperable and/or unresectable localized NSCLC. Efficacy, tolerance, relationship with dose and volumes (V20)

P-593 Preliminary results of phase II study of daily paclitaxel andcarboplatin administered concurrently with chest irradiation in stage III unresectable NSCLC

P-593 Preliminary results of phase II study of daily paclitaxel andcarboplatin administered concurrently with chest irradiation in stage III unresectable NSCLC

Phase II results of mitomycin and vinorelbine in second line chemotherapy for NSCLC

7321 Background: Second line chemotherapy using docetaxel is considered to be the standard therapy in advanced NSCLC. Single-agent activity of vinorelbine or mitomycin in patients with NSCLC was demonstrated previously in phase III trials. Methods: A Phase II single arm trial was completed, including 42 patients. All patients were pretreated with platinum containing chemotherapy according to treatment guidelines for unresectable NSCLC. Chemotherapy was given over 6 cycles (vinorelbine 25mg/m2 day 1 and 8, mitomycin 8mg/m2 day 1, q28 days). Primary end point of the study was survival. Results: For evaluation 42 patients were eligible (stage IIIB 17%, stage IV 83%). 5 patients had PR, 13 SD and 24 PD. Median survival was 8.5 months. 1-year follow up was completed in 39 patients. Based on Kaplan-Meier analysis the 1 year survival was 34%.Grade 3 and 4 adverse events were leukopenia (26.2%), anaemia (9.5%), nausea/vomiting (9.5%) and fatigue (2.4%). Thrombocytopenia grade 3 or 4 was not reported. Conclusion: Chemotherapy applying mitomycin and vinorelbine is effective in non chemonaive patients with advanced NSCLC. It gives promising results for survival and toxicity. However mitomycin specific toxicities have to be monitored. Compared to docetaxel the combination of mitomycin and vinorelbine shows an excellent cost-effectiveness. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration medac GmbH, Germany medac GmbH, Germany

Phase II trial of gemcitabine (G), carboplatin (C) and bexarotene (B) in patients (pts) with newly diagnosed, locally-advanced or metastatic non-small cell carcinoma of the lung (NSCLC)

7308 Background: The current standard of care for unresectable NSCLC is platinum-based chemotherapy. There is no benefit to adding together 3 or more cytotoxic agents, but adding a biologic agent may improve response rates and survival. B, a retinoic acid X-receptor agonist, is a differentiating agent with antineoplastic activity. Recent data suggests that the addition of B to platinum-based therapy may increase response rates and survival in NSCLC. Due to the poor outcome in this disease, we are studying a combination of G, C, and B as front-line therapy. Methods: Eligibility criteria includes histologically diagnosed NSCLC stage IIIB/IV; Karnofsky PS 70–100%; age ≥ 18, adequate bone marrow, renal and hepatic function, and written informed consent. Pts receive G, 1 g/m2 days 1 and 8 with C, AUC 5 (Calvert formula) on day 8. B, 400mg/m2 PO QD in divided doses is given days 1–28 of each treatment cycle. Pts may receive up to 6 cycles of chemotherapy or 2 cycles after CR achieved. Tumor restaging is performed every 2 cycles of therapy, in the absence of obvious rapid disease progression. Results: 19 pts have been enrolled; 10 males, 9 females; median age is 63.5 years (range 30–85 years). 2 pts had protocol violations (prior chemotherapy (1); small cell cancer on further pathologic evaluation (1)). A median of 2 cycles has been delivered (range 1–6). To date, the overall PR rate is 23.5% (4/17); 2 have had SD (1 progressed by cycle 4), for an overall clinical benefit rate of 35%. One is too early to evaluate. 18 pts to date are evaluable for toxicity. Thus far, the mean TTP is 68 days, and the mean OS is 142 days. The therapy has been well-tolerated with 7 pts experiencing Grade 2–3 myelosuppression (no febrile neutropenia), and 3 pts experiencing Grade 3–4 nausea and emesis. There have been no significant B-related adverse events. Conclusions: The addition of the differentiating agent B to a regimen of G and C is tolerable and active. In contrast to other studies, our early results suggest that the addition of B at this dose and schedule may add little to the clinical benefit observed with this regimen. Accrual continues in an effort to better define response rate and duration. No significant financial relationships to disclose.

Evaluation of safety and efficacy of ZD1839 as monotherapy for Chinese patients with advanced non-small cell lung cancer

7093 Background: The aim of the study was to evaluate the safety and efficiency of ZD1839 for Chinese patients with advanced NSCLC. Methods: From Dec 2002 to Aug 2003, 40 eligible patients with unresectable NSCLC (male 25, female 15, Aged from 28–85yrs, Bronchioloalveolar carcinoma 10, Other Adenocarcinoma 21, Squamous cell carcinoma 7, Unspecified 2)enrolled in the study. ZD1839 was administrated orally at the dose of 250 mg/day at about the same time everyday without interruption unless disease progressed or unacceptable adverse event occurred. The impact of treatment on disease-related symptoms and quality of life (QoL) was evaluated with Chinese version of EORTC QLQ-C30 and QLQ-LC13. Results: Daily oral dose of 250mg of ZD1839 was well tolerated in Chinese patients. Adverse events were generally mild (grade 1 and 2) and reversible. The most frequent adverse events were acne-like rash (62.5%) and diarrhea (30.0%). No patient withdrew from the study due to drug-related adverse event. The objective tumor response rate was 32.5%. Disease control rate was 62.5%. Multivariate analysis showed tumor response was associated with bronchioloalveolar carcinoma. The median progression-free survival (PFS) was 22.5w. At the data cutoff, 26 (65%) patients were still alive with median follow-up period of 30w (range: 2 to 60). The QoL response rates for five functioning scales and global QoL varied from 56% to 88%. Main symptom response rates varied from 44% to 84%. QoL and symptom response were correlated with objective tumor response. Conclusion: Our study showed the safety and efficacy of ZD1839 as monotherapy for Chinese patients with advanced NSCLC. Treatment with ZD1839 was associated with remarkable symptom release and improvement of QoL. Further clinical study with ZD1839 can be conducted in Chinese patients with NSCLC. No significant financial relationships to disclose.

Evaluation of safety and efficacy of ZD1839 as monotherapy for Chinese patients with advanced non-small cell lung cancer

7093 Background: The aim of the study was to evaluate the safety and efficiency of ZD1839 for Chinese patients with advanced NSCLC. Methods: From Dec 2002 to Aug 2003, 40 eligible patients with unresectable NSCLC (male 25, female 15, Aged from 28–85yrs, Bronchioloalveolar carcinoma 10, Other Adenocarcinoma 21, Squamous cell carcinoma 7, Unspecified 2)enrolled in the study. ZD1839 was administrated orally at the dose of 250 mg/day at about the same time everyday without interruption unless disease progressed or unacceptable adverse event occurred. The impact of treatment on disease-related symptoms and quality of life (QoL) was evaluated with Chinese version of EORTC QLQ-C30 and QLQ-LC13. Results: Daily oral dose of 250mg of ZD1839 was well tolerated in Chinese patients. Adverse events were generally mild (grade 1 and 2) and reversible. The most frequent adverse events were acne-like rash (62.5%) and diarrhea (30.0%). No patient withdrew from the study due to drug-related adverse event. The objective tumor response rate was 32.5%. Disease control rate was 62.5%. Multivariate analysis showed tumor response was associated with bronchioloalveolar carcinoma. The median progression-free survival (PFS) was 22.5w. At the data cutoff, 26 (65%) patients were still alive with median follow-up period of 30w (range: 2 to 60). The QoL response rates for five functioning scales and global QoL varied from 56% to 88%. Main symptom response rates varied from 44% to 84%. QoL and symptom response were correlated with objective tumor response. Conclusion: Our study showed the safety and efficacy of ZD1839 as monotherapy for Chinese patients with advanced NSCLC. Treatment with ZD1839 was associated with remarkable symptom release and improvement of QoL. Further clinical study with ZD1839 can be conducted in Chinese patients with NSCLC. No significant financial relationships to disclose.

A TLR9 CpG immunomodulator in combination with chemotherapy as treatment for advanced non-small cell lung cancer (NSCLS), a randomized, controlled phase II study

7126 Background: First line chemotherapy for unresectable NSCLC provides partial and short duration responses, and there are still 54,000 deaths/year in the U.S. CPG 7909 (ProMune), a new chemically defined, targeted immunomodulator acting through dendritic cell receptors is synergistic with chemotherapy in non-clinical models, and shows human anti-tumor activity in several cancers. Preclinical data, human safety at active doses, and the need to improve therapy justified a Phase 2 combination trial. Methods: This randomized, controlled study compares chemotherapy [C] (standard of care) alone vs. [C] plus CPG 7909. Seventy-five patients will be randomized 1:2, to [C] alone (taxane and platinum regimen given week 1 of each cycle) versus [C] plus CPG 7909, 0.20mg/kg administered subcutaneously weeks 2 and 3. The primary efficacy endpoint is anti-neoplastic activity determined by overall response rate (RECIST). Secondary efficacy assessments include clinical benefit, duration of response, time to progression, and survival. Multiple biologic responses parameters are compared between responders and non-responders. Results: Forty of 75 patients in 25 centers have been enrolled and treated to date. All have KPS > 70; the age range is 39–82, and 10 are female. Six patients are off-study (2= PD, 1= injection site reaction, 1= pulmonary emphysema, 1=exacerbation of gout, 1= angina and dyspnea) with 31 patients continuing therapy from 4 to 24 weeks. Toxicities of [C] are not complicated by CPG 7909. Tolerability is acceptable; no drug related serious adverse events have been reported to date, ongoing assessments show biologic responses consistent with CPG 7909 immunomodulatory activity, tolerance of the combination, and tumor response. Conclusions: This new combination regimen appears active in NSCLC treatment. Comparative tumor and biologic response profiles will be presented for both treatment groups. Author Disclosure Employment or Leadership Consultant or Advisory Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Coley Pharmaceutical Group Coley Pharmaceutical Group Coley Pharmaceutical Group

Weekly docetaxel-gemcitabine as first-line treatment in advanced non-small cell lung cancer: Preliminary results of a phase II study

7236 Background: Platinum based doublets are the standard of care for patients with advanced unresectable NSCLC and a good performance status. Non-platinum doublets have been investigated as an alt...

Weekly docetaxel-gemcitabine as first-line treatment in advanced non-small cell lung cancer: Preliminary results of a phase II study

7236 Background: Platinum based doublets are the standard of care for patients with advanced unresectable NSCLC and a good performance status. Non-platinum doublets have been investigated as an alternative to minimize toxicities. We report preliminary safety and efficacy results from a phase II study of weekly docetaxel and gemcitabine in such patients. Methods: Previously untreated patients with pathologically proven NSCLC and ECOG PS 0–1 and adequate organ functions were eligible. Docetaxel 36 mg/m2 IV and Gemcitabine 600 mg/m2IV were administered on D 1, 8, 15 of a 28 day cycle. Results: 26 patients were enrolled from December 2001 to date. Patients had a median age, 61 (Range 39–74); 13 were males; 2 had stage IIIB, 24 had stage IV. Of the 94 cycles (Median 3) administered, 40 were at full dose intensity, 51 required deletion of one week of treatment and 3 cycles required deletion of 2 weeks, mostly because of mylosuppresion. Treatment related grade 3 toxicities included: neutropenia in 34%, diarrhea in 15%, anemia in 4%, thrombocytopenia in 4% and mucositis in 4%. Atrial fibrillation and pulmonary embolism occurred in two patients each. There were no grade 4 hematological toxicities. There was 1 treatment related death due to pneumonia and 2 cases of hypersensitivity pneumonitis requiring hospitalization. Response rate was partial response 27 % (7/26), and stable disease 42% (11/26). Three patients (12%) were not evaluable for response. Median survival and progression free survival were not reached, but will be more than 8 months and 3.5 months respectively. Conclusions: Weekly docetaxel and gemcitabine is a well tolerated and active regimen in patients with advanced NSCLC, although this schedule was associated with frequent interruption secondary to myelosuppresion. Accrual to this study continues. Author Disclosure Employment or Leadership Consultant or Advisory Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Aventis Aventis; Eli Lilly Aventis

A TLR9 CpG immunomodulator in combination with chemotherapy as treatment for advanced non-small cell lung cancer (NSCLS), a randomized, controlled phase II study

7126 Background: First line chemotherapy for unresectable NSCLC provides partial and short duration responses, and there are still 54,000 deaths/year in the U.S. CPG 7909 (ProMune), a new chemically defined, targeted immunomodulator acting through dendritic cell receptors is synergistic with chemotherapy in non-clinical models, and shows human anti-tumor activity in several cancers. Preclinical data, human safety at active doses, and the need to improve therapy justified a Phase 2 combination trial. Methods: This randomized, controlled study compares chemotherapy [C] (standard of care) alone vs. [C] plus CPG 7909. Seventy-five patients will be randomized 1:2, to [C] alone (taxane and platinum regimen given week 1 of each cycle) versus [C] plus CPG 7909, 0.20mg/kg administered subcutaneously weeks 2 and 3. The primary efficacy endpoint is anti-neoplastic activity determined by overall response rate (RECIST). Secondary efficacy assessments include clinical benefit, duration of response, time to progression, and survival. Multiple biologic responses parameters are compared between responders and non-responders. Results: Forty of 75 patients in 25 centers have been enrolled and treated to date. All have KPS > 70; the age range is 39–82, and 10 are female. Six patients are off-study (2= PD, 1= injection site reaction, 1= pulmonary emphysema, 1=exacerbation of gout, 1= angina and dyspnea) with 31 patients continuing therapy from 4 to 24 weeks. Toxicities of [C] are not complicated by CPG 7909. Tolerability is acceptable; no drug related serious adverse events have been reported to date, ongoing assessments show biologic responses consistent with CPG 7909 immunomodulatory activity, tolerance of the combination, and tumor response. Conclusions: This new combination regimen appears active in NSCLC treatment. Comparative tumor and biologic response profiles will be presented for both treatment groups. Author Disclosure Employment or Leadership Consultant or Advisory Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Coley Pharmaceutical Group Coley Pharmaceutical Group Coley Pharmaceutical Group

O-126 High dose 3D conformal therapy in the treatment of inoperable and/or unresectable localized NSCLC. Tolerance, efficacy, relationship with the irradiated volumes (V20)

O-126 High dose 3D conformal therapy in the treatment of inoperable and/or unresectable localized NSCLC. Tolerance, efficacy, relationship with the irradiated volumes (V20)

3 Carboplatin based chemotherapy in unresectable and metastatic NSCLC — A single institution experience

3 Carboplatin based chemotherapy in unresectable and metastatic NSCLC — A single institution experience

P-590 A prognostic index for stage III unresectable NSCLC treated with chemoradiotherapy, and dose intensity as an important determinant of outcome

P-590 A prognostic index for stage III unresectable NSCLC treated with chemoradiotherapy, and dose intensity as an important determinant of outcome

Efficacy of modified regimen with attenuated doses of paclitaxel plus carboplatin combination chemotherapy in elderly and/or weak patients with advanced non-small cell lung cancer

Purpose: We conducted this study to evaluate the activity and toxicity of a combination regimen of paclitaxel plus carboplatin in patients with advanced NSCLC aged 65 years or older and/or in those with an ECOG performance status (PS) 2. Materials and methods: Chemotherapy-naive patients with unresectable pathologically-proven NSCLC and of either age ⩾65 or ECOG PS 2 were eligible. Patients received modified regimen with attenuated doses of paclitaxel (135 mg/m 2 i.v. for 3 h D1) and carboplatin (AUC=5, D1) every 3 weeks. Results: Thirty-five patients were enrolled. Nineteen patients were aged 65 or older (54%) and 26 patients (74%) were ECOG PS 2. The objective response rate was 40% with 14 partial responses. The median time to progression was 22 weeks. Grade 3 leucopenia occurred in 1 cycle and one case of neutropenic fever. Conclusions: The modified regimen with attenuated doses of paclitaxel plus carboplatin combination chemotherapy was effective and well tolerated in patients with advanced NSCLC aged 65 years or older and/or in those with ECOG PS 2.

A Phase III Randomized Trial of Combined Chemoradiotherapy Versus Radiotherapy Alone in Locally Advanced Non–Small-Cell Lung Cancer

A phase III randomized trial was conducted to investigate whether induction chemotherapy followed by radiation can influence survival as compared with radiation alone in unresectable, locally advanced non-small-cell lung cancer (LADNSCLC). A total of 101 patients with unresectable stage IIIA or IIIB NSCLC were enrolled. Patients were stratified by performance status, weight loss, histology and stage, and then randomized to receive combined chemoradiotherapy or radiotherapy alone. Radiotherapy was administered in 1.8 Gy to 2.0 Gy standard fractions daily 5 times weekly for a total dose of 60 Gy to 65 Gy. The combined group received induction of cisplatin, etoposide, and vinblastine (PEV) chemotherapy with cisplatin 20 mg/m2 on days 1 to 5, etoposide 100 mg/m2 on days 2 to 4, and vinblastine 6 mg/m2 on day 1, which wasrepeated every 3 weeks for 3 courses, after which time the patients underwent radiotherapy. Of 101 patients registered, 89 patients (43 combined, 46 radiotherapy alone) were eligible for analysis. The response rates for the combined and radiotherapy groups were 65% (28/43) and 70% (32/46), respectively. The median survival time (MST) showed a tendency to be more prolonged in the combined group than in the group receiving radiotherapy alone (13.8 vs. 8.5 months). The MST in patients with nonsquamous histology was strikingly prolonged in the combined group as compared with the radiotherapy group (14 vs. 3.6 months, p 0.027). Likewise, the MST in patients with stage IIIB was significantly prolonged in the combined group as compared with the radiotherapy group (11.1 vs. 7.2 months, p 0.045). Together, the MST of the high-risk group with nonsquamous or stage IIIB was significantly higher in the combined group than that seen in the radiotherapy group (11.6 vs. 8 months, p 0.046), whereas the MST of the low-risk group, defined as having both squamous histology and stage IIIA, was similar in the two treatment groups (18.3 vs. 20.8 months, p = 0.293). In conclusion, induction PEV chemotherapy plus radiotherapy is superior to radiotherapy alone in high-risk subsets of unresectable LAD-NSCLC and therapeutic strategy should be based on the identification of prognostic factors.

Induction therapy (IT) with paclitaxel (P) and CBDCA (C) followed by hyperfractionated radiotherapy (HFR) + weekly concurrent chemotherapy (WT) and subsequent manteinance therapy in unresectable NSCLC (Stage IIIA N2 bulky, Stage IIIB)

Induction therapy (IT) with paclitaxel (P) and CBDCA (C) followed by hyperfractionated radiotherapy (HFR) + weekly concurrent chemotherapy (WT) and subsequent manteinance therapy in unresectable NSCLC (Stage IIIA N2 bulky, Stage IIIB)