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© 2003 American Society for Clinical Oncology Consolidation Docetaxel After Concurrent Chemoradiotherapy in Stage IIIB Non–Small-Cell Lung Cancer: Phase II Southwest Oncology Group Study S9504
From the University of California, Davis Cancer Center, Sacramento, CA; Southwest Oncology Group Statistical Center and University of Washington, Seattle, WA; Loyola University Cancer Center, Maywood, IL; University of Colorado Health Sciences Center, Denver, CO; Sarah Cannon Cancer Center, Nashville, TN; Columbus Community Clinical Oncology Program, Columbus, OH; and Upstate Carolina Community Clinical Oncology Program, Spartanburg, SC. Address reprint requests to Southwest Oncology Group (SWOG-9504), Operations Office, 14980 Omicron Dr, San Antonio, TX 78245-3217.
Purpose: To test the concept of taxane sequencing in combined-modality therapy, this phase II trial (S9504) evaluated consolidation docetaxel after concurrent chemoradiotherapy in patients with pathologically documented stage IIIB non–small-cell lung cancer (NSCLC). Results were compared with those of the predecessor study (S9019) with identical eligibility, staging criteria, and treatment, excepting docetaxel consolidation. Patients and Methods: Treatment consisted of cisplatin 50 mg/m2 on days 1, 8, 29, and 36, etoposide 50 mg/m2 on days 1 through 5 and 29 through 33, and concurrent thoracic radiotherapy (total dose of 61 Gy). Consolidation docetaxel started 4 to 6 weeks after chemoradiotherapy at an initial dose of 75 mg/m2. Results: Stage subsets (tumor-node-metastasis system) in 83 eligible patients were as follows: T4N0/1, 31 patients (37%); T4N2, 22 patients (27%), and T1–3N3, 30 patients (36%). Concurrent chemoradiotherapy was generally well tolerated, but two patients died from probable radiation-associated pneumonitis. Neutropenia during consolidation docetaxel was common (57% with grade 4) and most frequent during escalation to 100 mg/m2. Median progression-free survival was 16 months, median survival was 26 months, and 1-, 2-, and 3-year survival rates were 76%, 54%, and 37%, respectively. Brain metastasis was the most common site of failure. In S9019, median survival was 15 months and 1-, 2-, and 3-year survival rates were 58%, 34%, and 17%, respectively. Conclusion: Consolidation docetaxel after concurrent chemoradiotherapy in stage IIIB NSCLC is feasible and generally tolerable, and results compare favorably with the predecessor trial S9019. Nevertheless, this study remains hypothesis-generating and does not provide definitive evidence of the benefit of this approach. Phase III trials evaluating the S9504 regimen have been initiated to validate these results.
LUNG CANCER is the most common cause of cancer-related death in both men and women in the United States. Patient survival is directly related to stage. Locally advanced (stage III) non–small-cell lung cancer (NSCLC), accounting for more than 40,000 cases annually, represents a heterogeneous group of patients and several clinically distinct substages.1 Treatment options for the majority of patients with stage III NSCLC include combinations of chemotherapy and thoracic radiation, with or without surgery. A number of randomized clinical trials and meta-analyses support the conclusion that combined modality approaches using cisplatin-based chemotherapy improve survival compared with radiotherapy alone in patients with surgically unresectable stage III disease.2–4 Depending on the strategy used, chemotherapy may play a cytotoxic role by eradicating distant micrometastases, a radiosensitizing role by improving local control, or both. Sequential approaches to chemoradiotherapy, in which platinum-based chemotherapy precedes thoracic radiation, have generally improved outcome by reducing distant failure rates. In contrast, in a phase III trial reported by Schaake-Koning,5 concurrent chemoradiotherapy using low-dose cisplatin was reported to improve survival by reducing local recurrence, without an effect on distant metastases. Most recently, two randomized trials, one by the West Japan Lung Cancer Group6 and the other by the Radiation Therapy Oncology Group (RTOG),7 have directly compared sequential and concurrent chemoradiotherapy regimens. Each demonstrated superior survival with the concurrent approach. In view of these observations, concurrent chemoradiotherapy paradigms integrating both radiosensitizing agents and dose levels of chemotherapy effective against micrometastases may prove to be most efficacious. Because distant metastases remain the major site of failure, it is also likely that more effective chemotherapy or other systemic antitumor agents will be required to further improve the current level of response and survival. Fortunately, several newly available chemotherapeutic agents are highly active against NSCLC, providing the basis for rational design of clinical trials integrating these agents into combined-modality therapy.8,9 Here we report the results of S9504, a Southwest Oncology Group (SWOG) phase II trial designed to maximize cytoreduction from chemoradiotherapy by delivering full-dose cisplatin and etoposide (PE) concurrently with thoracic radiation, followed by consolidation chemotherapy with docetaxel. The concept of taxane sequencing is currently being evaluated in other settings, including the adjuvant treatment of breast cancer.10 Testing this concept with consolidation docetaxel is a particularly interesting therapeutic strategy in stage III NSCLC because of the potential curability of this patient subset, the high level of activity of docetaxel in the primary treatment of metastatic NSCLC, its activity in second-line therapy, and molecular mechanisms of p53-independent apoptosis favoring administration before the emergence of clinical drug resistance.11–13 To isolate the effects of docetaxel and provide the basis for historical comparison, identical staging, eligibility criteria, and concurrent chemoradiotherapy were used as in the predecessor trial (S9019). Thus the only difference in treatment regimens between the two studies was substitution of docetaxel for PE during the consolidation phase of treatment.
Eligibility Criteria Eligibility criteria duplicated those of previous SWOG trials that evaluated stage IIIB disease amenable to combined-modality therapy (S8805 evaluated preoperative chemoradiotherapy and S9019 evaluated concurrent chemoradiotherapy).14,15 Histologic or cytologic proof of NSCLC was required. Pathologic diagnosis from involved mediastinal or supraclavicular lymph nodes alone was accepted if a distinct primary lesion was evident. Stage IIIB disease was assigned either by N3 (contralateral mediastinal or supraclavicular nodes) or by T4 from invasion of mediastinal structures, heart, great vessels, trachea, carina, esophagus, or vertebral body. Confirmation of T4 or N3 status was established according to T4 involvement found at the time of thoracotomy or thoracoscopy; involvement of the trachea or carina by bronchoscopy; unequivocal invasion of the heart, esophagus, aorta, or vertebral body by computed tomography (CT) scan, magnetic resonance imaging, or transesophageal ultrasound; or biopsy of supraclavicular or contralateral mediastinal N3 nodes. A substage designation of T4N0/1 required documentation of T4 status, with either a negative mediastinoscopy or no mediastinal nodes greater than 1 cm on CT scan. Patients with a T4 substage from malignant pleural effusion were ineligible. Patients with a performance status (PS) of 0,1, or 2 were eligible. Prestudy evaluation included history and physical examination; serum chemistries (lactate dehydrogenase, alkaline phosphatase, AST or ALT, bilirubin, albumin, and calcium); chest radiograph; CT of chest, liver, and adrenal glands; bone scan; and a contrast CT or magnetic resonance image of the brain. All patients had measurable or nonmeasurable but assessable disease and no prior therapy for NSCLC.
Additional eligibility criteria included a WBC count of Eligible patients had no serious medical illnesses precluding cisplatin-based chemoradiation and no other primary invasive cancer unless they had been disease-free for at least 5 years. All patients were informed of the investigational nature of this study and signed a written informed consent in accordance with local institutional review board and federal guidelines.
Study Design
Radiotherapy was identical to that of the predecessor trial S9019. The radiotherapy target volume was primary tumor plus a 1.5- to 2.0-cm margin, ipsilateral hilum, superior mediastinum, subcarinal nodes, and ipsilateral supraclavicular fossa. Treatment of the contralateral supraclavicular fossa was optional, unless it was involved. The contralateral hilum was excluded. Paraesophageal and inferior pulmonary ligament nodes were included if the lesion was in the lower lobe. Normal tissue tolerance criteria for the heart, spinal cord, and involved and uninvolved lung were mandated. The initial 45 Gy was delivered with 1.8-Gy fractions once daily Monday through Friday for 5 weeks without interruption by a linear accelerator generating at least 4-MeV photons, followed by a defined target boost volume at 2.0-Gy fractions each day to a total dose of 61 Gy, using 1.0- to 1.5-cm normal tissue margins. A short break of less than 1 week was allowed, but not required, for either severe esophagitis, weight loss
In the absence of progressive disease, consolidation docetaxel was initiated at 75 mg/m2 on cycle 1 and repeated every 3 weeks, with escalation to 100 mg/m2 during cycles 2 and 3 in the absence of protocol-defined toxicities (grade 4 neutropenia, febrile neutropenia, or Follow-up studies included a posttreatment CT scan at 4 to 6 weeks from completion of all chemotherapy. Subsequently, follow-up was every 2 months for 1 year, every 3 months for 3 years, then every 6 months. Patients were removed from the protocol for disease progression, unacceptable toxicity as assessed by the investigator, development of intercurrent, non–cancer-related illnesses precluding continued treatment, or on patient request.
Study Evaluation and Statistical Methods
The primary objective of S9504 was to estimate, within the limitations of a historical comparison, whether substitution of docetaxel for continued PE during the consolidation phase of treatment would improve survival compared with the predecessor trial S9019, and whether toxicities were acceptable. Eligibility criteria, staging requirements, and concurrent chemoradiotherapy were identical to S9019, providing the basis for comparison. The S9504 regimen would be considered promising if the median survival were increased by
Patient Characteristics S9504 was activated in October 1996 and closed to patient accrual in December 1998. Of 97 patients entered, seven patients were ineligible because of stage IV disease (one patient with brain metastases, one patient with bone metastases, one patient with intra-abdominal metastases, and four patients with lung metastases), and seven were ineligible because of inadequate staging to document stage IIIB or rule out stage IV disease (no CT scan of abdomen or brain, failure to document involvement of enlarged mediastinal nodes, or T4 status). This rate of ineligibility is similar to that of S9019. Characteristics and stage subsets of 83 eligible patients in S9504 are listed in Table 1  , along with 50 eligible patients in S9019. The median age in S9504 was 60 years, with a range from 34 to 80 years. Sixty-one patients were male and 22 were female. PS was 0 to 1 in 78 patients and 2 in five patients. Stage distribution in S9504 was as follows: T4N0/1, 31 patients (37%); T4N2, 22 patients (27%); and N3, 30 patients (36%).
Treatment Delivery Seventy-four patients (88%) on S9504 completed concurrent chemoradiotherapy. Failure to complete concurrent therapy was attributed to the following causes: toxicity (five patients), progressive disease (two patients), death unrelated to treatment or progressive disease (one patient), and postobstructive pneumonia (one patient). Sixty-five patients (78%) proceeded to consolidation docetaxel. Reasons for not proceeding to consolidation therapy were as follows: progressive disease on restaging after concurrent therapy in three patients, residual side effects in one patient, inadequate restaging in four patients, and patient refusal unrelated to toxicity in one patient. Eight patients had the dose of docetaxel reduced on cycle 2 because of toxicity during cycle 1. Thirty-nine consolidation patients (57%) were dose escalated to 100 mg/m2 as per protocol, whereas 17 remained at 75 mg/m2 for the following reasons: grade 4 neutropenia (three patients), febrile neutropenia (two patients), grade 3 nonhematologic toxicity (two patients), misdosing (two patients), and no reason given (eight patients). Forty-nine patients (75% of those starting consolidation) received all three cycles of docetaxel; 28 patients (41%) at the intended dose schedule (ie, 75 mg/m2 on cycle 1 and escalated to 100 mg/m2 on cycles 2 and 3).
Toxicity
Response Best radiographic response was determined on an intent-to-treat basis for all eligible patients in S9504 (Table 3 ). By CT scan criteria, the complete and partial response rates were 7% and 60%, respectively, for an overall response rate of 67% (95% CI, 56% to 77%). Stable disease and progressive disease occurred in 19 patients (23%) and eight patients (10%), respectively. Five patients with no or an inadequate reassessment were considered nonresponders and were included in the stable disease category. Response was not considered a primary end point in S9019 and was not assessed.
Time to Progression and Survival Analysis With a median follow-up of 32 months, median progression-free survival based on radiographic criteria was 16 months (95% CI, 10 to 17 months). Unresolved pleural or pericardial effusions not otherwise specified were considered evidence of progressive disease at the discretion of the treating physician, regardless of subsequent outcome.
Survival is displayed by Kaplan-Meier plot in Fig 1
Sites of First Failure Among 45 reported sites of first failure, 24 (53%) were distant, 16 (36%) were local-regional, and five (11%) were both local-regional and distant (Table 5 ). The brain was a site of first failure in 15 patients (33%), or 62.5% of the 24 patients with distant sites of first failure. Isolated brain metastasis was reported in eight patients; 18% of the total, or 33% of distant failures.
At present, no one chemoradiotherapy regimen can be considered standard of care in surgically unresectable stage III NSCLC. Randomized trials reported by the West Japan Group and RTOG indicate that concurrent chemoradiation should supplant sequential administration.6,7 However, these trials were designed and implemented before the availability of newer chemotherapeutic agents with relatively high levels of activity against NSCLC, such as paclitaxel, docetaxel, gemcitabine, and vinorelbine.8,9 Consequently, clinical research efforts have focused on incorporating newer chemotherapeutic agents, either singly or in combination with a platinum compound, into concurrent chemoradiation regimens for locally advanced NSCLC. A large number of pilot studies have been reported, many of which have shown encouraging results.17–20 However, for many newer chemotherapeutic agents, dose-limiting toxicities require that lower doses be given during the concurrent phase.21,22 In particular, a recently published trial by Vokes et al22 testing the feasibility of delivering newer chemotherapeutics with concurrent chest radiation reported a 52% incidence of grade 3/4 esophagitis in the gemcitabine/cisplatin treatment arm, despite gemcitabine dose reduction during chemoradiation. Thus, the issue of how to best address the dual goals of local control and eradication of distant micrometastases while avoiding excessive toxicity remains controversial. Specifically, although delivery of full-dose chemotherapy may be required to reduce distant failure rates, toxicities such as esophagitis or pneumonitis may necessitate lowering chemotherapy doses during concurrent administration of thoracic irradiation. Recently, two mirror-image treatment paradigms have emerged that may optimize delivery of chemotherapy and radiation for stage III NSCLC: induction chemotherapy followed by concurrent chemoradiation (induction-first), and concurrent chemoradiation followed by consolidation chemotherapy (concurrent-first).23,24 Although these approaches have not been compared in a phase III setting, a randomized phase II trial by Choy et al24 compared three treatment arms: first, sequential therapy with paclitaxel/carboplatin followed by thoracic radiation; second, the same chemotherapy given as induction-first followed by concurrent therapy; and third, concurrent-first followed by consolidation paclitaxel/carboplatin. The preliminary results of this study showed that the induction-first strategy resulted in reduced delivery of concurrent chemoradiation and numerically lower survival. Although a recently completed Cancer and Leukemia Group B phase III trial directly compared concurrent chemoradiation alone with induction-first, results are not yet available. In S9504, we sought to build on the SWOG database evaluating the concurrent-first approach by substituting docetaxel for further PE during the consolidation phase of therapy. PE, although representing older chemotherapy, is particularly well suited for use during the concurrent phase because it can be delivered in full dose together with thoracic irradiation. In fact, PE and concurrent radiotherapy have been the core of therapy in limited-stage small-cell lung cancer in the United States for many years. Similarly, docetaxel is conceptually attractive for use during consolidation therapy. The level of single-agent activity of docetaxel in chemotherapy-naive patients with metastatic NSCLC is arguably the highest of any of the newer chemotherapeutic agents.25 Phase II studies have also documented that docetaxel possesses second-line activity in NSCLC, even in patients who experienced treatment failure with prior cisplatin-based regimens.26 For example, in a multi-institutional trial of 80 patients reported by Gandara et al,27 docetaxel demonstrated a similar response rate in platinum-refractory and platinum-sensitive patient subsets. Most important, in a phase III study, docetaxel-treated patients had a longer time to progression and survival and superior quality of life compared with patients randomly assigned to best supportive care alone.28 In addition, in preclinical models, docetaxel was active against tumors with p53 mutation and demonstrated potential molecular mechanisms of action, such as Bcl-2 phosphorylation and p27 induction, that theoretically favor administration after DNA-damaging chemoradiation.29,30 We hypothesized that clinical application of the concept of taxane sequencing with consolidation docetaxel would improve survival after maximal cytoreduction with concurrent chemoradiation in potentially curable stage IIIB NSCLC.
To provide a prospective basis for historical comparison, identical eligibility criteria, staging, and documentation procedures for T4 or N3 status were used in S9504 and the predecessor trial S9019.31,32 Indeed, patient characteristics and stage subsets are remarkably similar between the two studies (Table 1 As in other recent studies of combined-modality therapy for NSCLC, the brain was a major site of treatment failure.10,13 Eight patients (18% of the total or 33% of the distant sites of first failure) experienced relapse in the brain only. This observation raises the question of whether prophylactic cranial irradiation (PCI) should be used, similar to common practice in limited-stage SCLC. An RTOG study will address this question directly by randomly assigning patients to PCI or observation after combined-modality therapy in stage III NSCLC. At the time S9504 was designed, the optimal dose of docetaxel was considered to be 100 mg/m2. Subsequently, additional studies have indicated that a dose level of 75 mg/m2 is equally effective and less toxic.26,28 Indeed, neutropenia during consolidation docetaxel in this trial was most prominent after escalation to 100 mg/m2. Therefore, in subsequent studies evaluating this regimen, a docetaxel dose of 75 mg/m2 is used in all consolidation cycles. Although we hypothesize that systemically effective dose levels of docetaxel are required during consolidation to adequately address the issue of distant micrometastases, this phase II trial cannot speak to whether other taxanes such as paclitaxel would be equally effective in this setting, or even whether other drug classes used in consolidation therapy would achieve equivalent results. The question of consolidation therapy itself is being addressed by a randomized phase III trial discussed below.
Response was not assessed in S9019 and thus cannot be compared between the two studies. However, time to progression and survival data favor S9504 (Table 4
In conclusion, the results of S9504 compare favorably with the predecessor trial S9019. Confirmation is required, and two randomized trials have been designed for this purpose. Participation in these important studies is highly encouraged. Lastly, the high incidence of brain relapse raises the issue of whether PCI should be used in patients with stage III NSCLC treated with curative intent. This question will also be addressed by an Intergroup trial now in development.
This investigation was supported in part by the following Public Health Service Cooperative Agreement grant numbers awarded by the National Cancer Institute, Department of Health and Human Services: CA38926, CA32102, CA46441, CA46282, CA42777, CA22433, CA35261, CA35119, 20319, CA76448, CA67663, CA35176, CA52386, CA20319, CA15377, CA45377, CA58861, CA14028, CA45807, CA35192, CA12644, CA45560, CA35431, CA35128, CA46368, CA04919, CA63844, CA46136, CA16385, CA46113, CA74647, and CA58415.
1. Edelman MJ, Gandara DR, Roach M, et al: Multi-modality therapy in stage III non-small cell lung cancer. Ann Thor Surg 61:1564–1572, 1996
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4. Non-Small Cell Lung Cancer Collaborative Group: Chemotherapy in non-small cell lung cancer: A meta-analysis using updated data on individual patients from 52 randomized clinical trials. Br Med J 311:899–909, 1995 5. Schaake-Koning C, van den Bogaert W, Dalesio O, et al: Effects of concomitant cisplatin and radiotherapy on inoperable non-small cell lung cancer. N Engl J Med 326:524–530, 1992[Abstract]
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8. Lilenbaum RC, Green MR: Novel chemotherapeutic agents in the treatment of non-small cell lung cancer. J Clin Oncol 11:1391–1402, 1993 9. Edelman MJ, Gandara DR: Promising new agents in the treatment of non-small cell lung cancer. Cancer Chemother Pharmacol 37:385–393, 1996[CrossRef][Medline] 10. Henderson IC, Berry D, Demetri G, et al: Improved disease-free (DFS) and overall survival (OS) from the addition of sequential paclitaxel (T) but not from the escalation of doxorubicin (A) dose level in the adjuvant chemotherapy of patients (PTS) with node-positive primary breast cancer (BC). Proc Am Soc Clin Oncol 17:101a, 1998 (abstr 390A) 11. Goldberg Z, Gaspar L, Lara R, et al: Combined modality treatment of non-small cell lung cancer, in Pass HI (ed): Lung Cancer Principles and Practice Updates. Philadelphia, PA, Lippincott, Williams, and Wilkins, 2001, pp 1–11 12. Edelman M, Gandara DR, Lau D, et al: Sequential combination chemotherapy in patients with advanced non-small cell lung carcinoma. Cancer 92:146–152, 2001[CrossRef][Medline]
13. Gandara DR, Vokes E, Green M, et al: Activity of docetaxel in platinum-treated non-small cell lung cancer: Results of a phase II multicenter trial. J Clin Oncol 18:131–135, 2000
14. Albain KS, Rusch VW, Crowley JJ, et al: Concurrent cisplatin/etoposide plus chest radiotherapy followed by surgery for stages IIIA (N2) and IIIB non-small cell lung cancer: Mature results of SWOG 8805. J Clin Oncol 13:1880–1892, 1995
15. Albain KS, Crowley JJ, Turrisi AT, et al: Concurrent cisplatin, etoposide plus radiotherapy for pathologic stage IIIB non-small cell lung cancer: A Southwest Oncology Group phase II study (S9019). J Clin Oncol 20:3454–3460, 2002 16. Kaplan E, Meier P: Nonparametric estimation from incomplete observations. J Am Stat Assoc 53:457–481, 1958[CrossRef]
17. Choy H, Akerley W, Safran H, et al: Phase I trial of outpatient weekly paclitaxel and concurrent radiation therapy for advanced non-small-cell lung cancer. J Clin Oncol 12:12:2682–2686, 1994 18. Belani CP, Aisner J, Day R, et al: Weekly paclitaxel and carboplatin with simultaneous thoracic radiotherapy for locally advanced non-small cell lung cancer: Three year follow-up. Proc Am Soc Clin Oncol 16:448a, 1997 (abstr 1608) 19. Choy H, Akerley W, Safran H, et al: Multi-institutional phase II trial of paclitaxel, carboplatin and concurrent radiation therapy for locally advanced inoperable non-small cell lung cancer. J Clin Oncol 16:3316–3322, 1998[Abstract]
20. Lau D, Leigh B, Gandara DR, et al: Twice weekly paclitaxel and weekly carboplatin with concurrent thoracic radiation followed by carboplatin/paclitaxel consolidation for stage III non-small cell lung cancer: A California Cancer Consortium phase II trial. J Clin Oncol 19:442–447, 2001 21. Zinner R, Fossella F, Komaki R, et al: Phase I trial of concurrent gemcitabine (G) plus chest radiotherapy (XRT), followed by consolidation systemic chemotherapy with G plus cisplatin (CDDP), for patients with stage III and medically inoperable stage II non-small cell lung cancer (NSCLC). Proc Am Soc Clin Oncol 18:466a, 1999 (abstr 1798)
22. Vokes EE, Herndon JE, Crawford J, et al: Randomized phase II study of cisplatin with gemcitabine or paclitaxel or vinorelbine as induction chemotherapy followed by concomitant chemoradiotherapy for stage IIIB non-small-cell lung cancer: Cancer and Leukemia Group B Study 9431. J Clin Oncol 20:4191–4198, 2002 23. Gandara DR, Edelman M, Lara P, et al: Evolution of combined modality therapy for stage III non-small cell lung cancer. Oncology 14:35–41, 2000 (suppl) 24. Choy H, Curran WJ, Scott CB, et al: Preliminary report of locally advanced multimodality protocol (LAMP): ACR 427: A randomized phase II study of three chemo-radiation regimens with paclitaxel, carboplatin, and thoracic radiation (TRT) for patients with locally advanced non small cell lung cancer (LA-NSCLC). Proc Am Soc Clin Oncol 21:291a, 2002 (abstr 1160) 25. Fossella FV: Docetaxel in the treatment of non-small cell lung cancer: Review of single-agent trials. Semin Oncol 26:17–23, 1999 (suppl 16)[Medline]
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29. Blagosklonny M, Schulte TW, Nguyen P, et al: Taxol-induced apoptosis and phosphorylation of Bcl-2 protein involves c-Raf-1 and represents a novel c-Raf-1 signal transduction pathway. Cancer Res 56:1851–1854, 1996 30. Gumerlock PH, Mack PC, Manorek GH, et al: Bcl-2 phosphorylation and p27 induction as potential p53-independent mechanisms of apoptotic response to taxanes in non-small cell lung carcinoma. Proc Am Assoc Cancer Res 40:739, 1999 (abstr 4879) 31. Gandara DR, Lovato LC, Albain KS, et al: Pathological stage IIIb non-small cell lung cancer (NSCLC): Prolonged survival with consolidation of docetaxel following concurrent chemoradiotherapy (SWOG 9504). Lung Cancer 29:92, 2000 (abstr 302) 32. Gaspar L, Gandara D, Chansky K, et al: Consolidation docetaxel following concurrent chemoradiotherapy in pathologic stage IIIb non-small cell lung cancer (NSCLC) (SWOG 9504): Patterns of failure and updated survival. Proc Am Soc Clin Oncol 20:315a, 2001 (abstr 1255) 33. Koukourakis MI, Kourousis C, Kamilaki M, et al: Weekly docetaxel and concomitant boost radiotherapy for non-small cell lung cancer: A phase I/II dose escalation trial. Eur J Cancer 34:838–844, 1998[Medline] 34. Scagliotti GV, Manegold C, Buchholz E, et al: Randomized phase II study evaluating the feasibility of thoracic radiotherapy with or without weekly docetaxel (Taxotere) following induction chemotherapy with cisplatin (DDP) and docetaxel in unresectable stage IIIA/B non-small cell lung cancer. Proc Am Soc Clin Oncol 21:320a, 2002 (abstr 1279) 35. Schwarzenberger PO, Barron S, Wynn R, et al: Docetaxel chemosensitization with once weekly, hypofractionated thoracic radiation. Proc Am Soc Clin Oncol 21:211b, 2002 (abstr 2662) 36. Thirion P, McGibney C, Holmberg O, et al: 3-Dimensional conformal radiation therapy (3DCRT) permits radiobiological dose escalation for non-small-cell lung cancer (NSCLC): Preliminary results of a phase I/II Trial. Proc Am Soc Clin Oncol 20:344a, 2001 (abstr 1373) Submitted April 30, 2002; accepted March 7, 2003.
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Copyright © 2003 by the American Society of Clinical Oncology, Online ISSN: 1527-7755. Print ISSN: 0732-183X
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ABSTRACT
INTRODUCTION
4,000/mL, platelets above institutional lower limits of normal, hepatic function at or below 1.5 x institutional upper limits of normal, and a creatinine clearance 
