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© 2001 American Society for Clinical Oncology Multicenter Phase II Trial of Paclitaxel, Cisplatin, and Etoposide With Concurrent Radiation for Limited-Stage Small-Cell Lung CancerBy m
From the Departments of Oncology and Pulmonology, University Hospital of Troms
Address reprint requests to Roy M. Bremnes, MD, Department of Oncology, University Hospital of Troms
PURPOSE: To investigate the feasibility, efficacy, and safety of adding paclitaxel to cisplatin/etoposide chemotherapy and concurrent thoracic radiotherapy (TRT) in treatment of limited-stage small-cell lung cancer (LD-SCLC). PATIENTS AND METHODS: Patients received five courses of chemotherapy (paclitaxel 175 mg/m2 1-hour intravenous [IV] infusion day 1; cisplatin 50 mg/m2 IV day 1; etoposide 100 mg/m2 IV day 1; oral etoposide 100 mg bid days 2 to 5) at 3-week intervals. TRT (42 Gy administered in 15 fractions) was administered concurrent with chemotherapy cycle 3. All patients were evaluated before starting TRT and 4 weeks after termination of chemotherapy. Patients achieving complete remission (CR) were administered prophylactic cranial irradiation. RESULTS: Thirty-nine patients were included, and the median age was 63 years. The median follow-up was 36 months (range, 19 to 57 months). The overall response rate was 92% (CR, 81%; partial response, 11%), and the median survival was 21 months. The 1- and 2-year disease-specific survival rates were 69% and 37%, respectively. Of 29 CR patients, 83% have relapsed. Brain metastasis was as frequent as local recurrences (42%). Hematologic toxicity included grade 3 to 4 leukopenia in 74% of patients and grade 3 thrombocytopenia in 10%. One treatment-related death occurred as a result of severe neutropenia and septicemia. Hematotoxicity caused dose reductions in 31% of courses. One patient had an anaphylactic reaction during the first paclitaxel infusion. Paclitaxel-related neuropathy and myalgia were reversible. Grade 3 esophagitis was seen in five patients during and shortly after TRT. CONCLUSION: This novel multimodal regimen is effective and well tolerated in patients with LD-SCLC. It compares favorably with previously published phase II studies.
SMALL-CELL LUNG cancer (SCLC) accounts for 20% to 25% of all lung cancers. It is a common malignancy that is rapidly fatal if left untreated (< 3 months). Although SCLC is highly responsive to both chemo- and radiotherapy, the majority of patients will ultimately relapse and die of treatment-resistant disease. Today, long-term survival is achieved in only 3% to 8%.1,2 Limited-stage SCLC (LD-SCLC), which constitutes approximately 40% of all SCLC, is considered potentially curable. Among patients treated with combination chemotherapy and thoracic radiotherapy (TRT), 7% to 15% experience long-term progression-free survival. Since the introduction of combination chemotherapy for SCLC in the 1970s, there has been definite progress in improving the outcome of the disease. The combination of etoposide and cisplatin has been considered the standard chemotherapy regimen in the treatment of LD-SCLC since the late 1980s.3-7 The value of TRT in SCLC has been discussed for years. The results from two meta-analyses evaluating the survival benefit of TRT in SCLC were published in the early 1990s.8,9 Both studies reported a statistically significant improvement in survival by using TRT in LD-SCLC. Consequently, TRT is considered part of the routine treatment for LD-SCLC.1,6,10 Lately, prophylactic cranial radiation (PCI) has come into routine clinical use for LD-SCLC patients achieving complete remission (CR) during treatment. PCI has been shown to approximately halve the rate of recurrences in the brain and to improve the survival rate by approximately 5%.11-13 For the majority of patients, there is no association between modern PCI and neuropsychometric impairment.12,14 A number of anticancer agents with novel mechanisms of action have recently been developed. One such agent, paclitaxel, has demonstrated excellent single-agent activity against SCLC with 43% to 68% response rates.15,16 These data, along with in vitro data indicating that paclitaxel is an effective radiosensitizer,17,18 have prompted investigators to evaluate optimal paclitaxel-containing chemotherapy regimens combined with TRT for the treatment of LD-SCLC. The objectives of the present phase II study were to assess the efficacy, tolerability, and feasibility of adding paclitaxel to the combination of etoposide, cisplatin, and concurrent TRT, which hitherto has been considered the standard treatment regimen in SCLC.
This investigation was a national, prospective, open, phase II study in which the efficacy, toxicity, and feasibility of adding paclitaxel to etoposide, cisplatin, and concurrent thoracic radiation were to be assessed. Our working hypothesis was that the addition of paclitaxel to our standard chemotherapy combination (etoposide and cisplatin [EP]) and concurrent TRT would enhance cytotoxicity, increase the beneficial irradiation effect, and thus have a beneficial impact on survival. The primary end point was 2-year survival. Secondary end points were objective response rates, disease-free survival (DFS), and toxicity.
Eligibility Criteria Limited disease was defined as malignancy confined to one hemithorax and adjacent nodes, being treatable by radiotherapy field sizes (portals) tolerated by normal tissue. Patients with pleural effusion with positive cytology were considered ineligible. The study was approved by the Regional Ethics Committee and the National Drug Administration. All patients provided written, informed consent before enrollment, and study data were subjected to monitoring.
Staging
Treatment TRT was given as an anterior and posterior portal individually encompassing the regional mediastinal lymph nodes and the primary site with a 1.5- to 2-cm margin. The portal explicitly encompassed the original tumor volume of the primary site with the recommended margin. The supraclavicular region was not routinely treated unless palpable nodes or the primary tumor were located in the apical region of the lung. The radiation therapy was administered for 3 weeks between the third and fourth chemotherapy courses. Fractionation was 15 fractions, with 2.8 Gy once daily (total, 42 Gy). A 1.0-cm-wide filter was inserted in the posterior field to reduce the medulla dose to 2.6 Gy per fraction and thereby not exceed an equivalent dose value of 1,180 ret. PCI was administered to all patients classified as CR at restaging, 4 weeks after ending chemotherapy treatment. PCI was started within 2 weeks after restaging and was administered as a total of 30 Gy to the whole brain (two opposing fields), using 2-Gy once-daily fractions (15 total fractions).
Dose Modifications
Blood counts on treatment days were used to assess whether chemotherapy should be delayed. If leukocytes were
Evaluation
Statistics
Between March 1996 and October 1998, 39 LD-SCLC patients at four university hospitals in Norway were included in this trial. The median age was 63 years (range, 40 to 75 years). Further patient characteristics are given in Table 1. The majority of patients (54%) were male. There was only one patient (3%) with a World Health Organization performance status of 2, and the others were equally distributed between performance statuses of 0 and 1. The mean tumor size was 6.2 cm (range, 2 to 16 cm). Ten percent (n = 4) were clinically considered N0, whereas 74% (n = 29) of the cases were N2 or higher. The N0 cases were considered inoperable. Before treatment, 26% of the patients (seven males and three females) were anemic. At inclusion, elevated NSE, lactate dehydrogenase, alkaline phosphatase, and gamma-glutamyl transferase were found in 69%, 18%, 18%, and 26% of the patients, respectively. The mean serum NSE at inclusion was 32.9 µg/L (range, 7 to 93 µg/L), and after completion of therapy, 9.3 µg/L (range, 5 to 47 µg/L).
The median follow-up time after treatment cessation was 36 months (range, 19 to 57 months). All 39 included patients were evaluated on an intent-to-treat basis with regard to survival and toxicity. A total of 175 chemotherapy courses were administered. Sixty-nine percent (n = 121) of the courses were given at full doses, and 32 (82%) of the included patients received the intended protocol chemotherapy. Seven patients received less than five courses due to the following: (1) major toxicity or death (n = 3); (2) protocol treatment termination due to SD or PD before their third chemotherapy course (n = 3); or (3) fatal bronchial bleeding during radiotherapy (n = 1).
Response and Survival Rates Of the assessable patients, the overall response rate (ORR) was 92%. CR and PR were achieved in 81% (n = 29) and 11% (n = 4) of patients, respectively. Patients demonstrated rapid responses after initiation of chemotherapy. Ninety-two percent experienced minimum PR within the third chemotherapy course (before TRT). All patients (n = 39) were included in the survival analysis. The median survival was 21 months. The 1- and 2-year disease-specific survival rates were 69% and 37%, respectively (Fig 1). Disease-specific survival rates were calculated after exclusion of two cardiovascular deaths (both patients without evidence of SCLC). The overall survival rates at 1 and 2 years were 67% and 33%, respectively. The median DFS time was 8 months, and the 2-year DFS rate was 11% (Fig 2).
Treatment Failure and Patient Relapse Initial treatment failures were experienced by three patients (SD, n = 1; PD, n = 2). Of the two patients who progressed, one experienced a local failure, and the other developed a supraclavicular metastasis despite a profound local response. Of 29 patients who attained CR, 83% (n = 24) had relapsed by October 2000. The primary sites of relapse were as follows: brain (n = 10), local (n = 10), liver (n = 2; one patient also had intraspinal and leptomeningeal metastases), supraclavicular (n = 1), and bone (n = 1). PCI was administered to only 76% (n = 22) of patients in CR. Seven CR patients did not receive PCI because of protocol violation (n = 3) or as a result of incorrect classification as PR (n = 4). Among CR patients without PCI, 86% (n = 6) developed brain metastasis, whereas this occurred in only 18% (n = 4) of CR patients given PCI.
Toxicity and Dose Reductions
With regard to nonhematologic toxicity, hypersensitivity reactions were reported in four patients. In one patient, the treatment was terminated during the first paclitaxel infusion because of an anaphylactic reaction. The observed neurotoxicity and myalgia were completely reversible. During and after thoracic radiotherapy, 20 patients reported some degree of esophagitis. Grades 1, 2, and 3 esophagitis were reported by seven, eight, and five patients, respectively. There were no reports of grade 4 esophagitis. Grade 3 esophagitis was only seen during and immediately after TRT. Dose reductions due to hematologic toxicity were performed in 31% (n = 55) of the chemotherapy courses. In patients in whom dose reductions were necessary, reduced doses were usually administered for cycles 2 through 5. Dose reductions were evenly spread over cycles 2, 3, 4, and 5. After radiotherapy, the fourth chemotherapy course was delayed in 26% of patients (n = 10), with a mean delay of 1.4 weeks. In three patients, the delay was caused by esophagitis, whereas the other delays (n = 7) were due to hematotoxicity and in part reduced performance status.
As a result of the significant sensitivity to anticancer agents, SCLC was believed in the 1970s to be one of the first solid malignancies to be cured by chemotherapy.19 Thirty years and numerous clinical trials later, this optimism has turned to nihilism for many clinicians. In LD-SCLC, the addition of chest TRT and PCI has rendered an important though modest increase in survival rates during the last 20 years. Yet there has been no survival improvements related to chemotherapy since the EP regimen was introduced in the late 1980s.3-5,20,21 Since SCLC usually presents as disseminated disease, treatment strategies even in limited-stage disease have focused largely on systemic therapy. Combination chemotherapy has produced high response rates, but most patients have eventually developed treatment-resistant recurrences, and survival outcomes have been disappointing.10 To counteract the development of resistant clones, several strategies have been followed: (1) maintenance chemotherapy beyond four to six cycles, (2) maximizing dose-intensity with or without colony-stimulating factors, (3) alternating chemotherapy regimens, and (4) high-dose chemotherapy. Because no strategy has been successful,7 one approach to this problem has been incorporation of new anticancer agents with high single-agent activity into standard regimens. Among several new antineoplastic agents with a novel mechanism of action, paclitaxel has appeared as one of the most promising in SCLC. It has demonstrated significant single-agent response rates and is an effective radiosensitizer.15-18 Several phase I/II studies in SCLC, employing paclitaxel-containing chemotherapy regimens, have demonstrated impressive response rates. The most extensive experience in LD-SCLC has been reported by Hainsworth et al.22,23 In their initial trial, they used four cycles of paclitaxel 135 mg/m2 (1-hour IV infusion, day 1), carboplatin area under the curve of 5 (IV, day 1), and oral etoposide 50 mg alternating with 100 mg (days 1 to 10). Concurrent TRT (45 Gy administered in 1.8-Gy fractions) was started after chemotherapy course 3. In 15 LD-SCLC patients, the ORR was 93% (CR, 40%), and the median survival was 17 months.22 In their next study,23 chemotherapy doses were escalated (paclitaxel 200 mg/m2 and carboplatin area under the curve of 6). In 41 LD-SCLC patients, the ORR was 98% (CR, 71%), and the median survival was 20 months. As expected, the myelosuppression was more severe at the higher dose level, with grade 3 to 4 leukopenia in 71% of the patients. Gatzemeier et al24 evaluated the same three-drug regimen in LD-SCLC (paclitaxel 175 mg/m2, 1-hour IV infusion). TRT was not administered. The ORR was 88%, but only 37% achieved CR. Survival data were not given. The toxicity was reported to be moderate, and the regimen, well tolerated. In a phase I/II study recently reported by Levitan et al,25 31 LD-SCLC patients received combination chemotherapy with paclitaxel, etoposide, and cisplatin (four courses). For the first two courses (concomitant with TRT, 45 Gy administered in 1.8-Gy fractions), the paclitaxel dose was 135 mg/m2. For cycles 3 and 4, the dose was fixed at 170 mg/m2. G-CSF was routinely administered. The ORR was 96%, whereas 39% attained CR. Median survival was 22 months. The Eastern Cooperative Oncology Group26 evaluated the combination of paclitaxel (170 mg/m2, 3-hour IV infusion), etoposide, and cisplatin with concurrent high-dose TRT in LD-SCLC. G-CSF was administered in cycles 1 and 2. Radiation therapy (63 Gy administered as 1.8-Gy fractions) was administered concurrently with cycles 3 and 4 (reduced paclitaxel dose, 135 mg/m2). In 61 assessable patients, the ORR was 64% (CR, 13%), and the 1-year survival rate was 63%. We concluded that the combination of paclitaxel, etoposide, and cisplatin with concurrent high-dose TRT was well tolerated. The median survival was not reached during a follow-up of 11.4 months. The Radiation Therapy Oncology Group27 investigated the same three-drug regimen (paclitaxel 135 mg/m2, 3-hour IV) combined with twice-daily TRT in LD-SCLC patients. TRT (45 Gy administered as 1.5 Gy fractions bid) was administered concurrently with the first cycle. Of 51 assessable patients, 78% achieved CR. The 1-year survival rate was 83%, and the median survival (not reached) was estimated to exceed 30 months. Based on the experiences of Hainsworth et al23,28,29 and Bunn and Kelly,30 we chose to use paclitaxel at a dose of 175 mg/m2 (1-hour IV infusion) for this study. In consideration of an enhanced hematotoxicity, neurotoxicity, and radiosensitizing effect by adding paclitaxel, cisplatin and etoposide doses were slightly reduced compared with the standard doses of these drugs. Our treatment results are equivalent to other phase II trials of paclitaxel in LD-SCLC.22-27 The 92% ORR in our trial was within the upper range (ORR, 64% to 98%) of comparable trials, and the CR rate was slightly higher (81% v 13% to 78%). In some of the comparable studies, the paclitaxel dose was significantly lower, or radiotherapy was not given. At the Sarah Cannon Cancer Center,23 dose escalation of paclitaxel and carboplatin resulted in a significant increase of the CR rate. The median survival of 17 to 22 months reported by Hainsworth et al22,23 and Levitan et al25 is similar to our data. Regarding the impressive number of CR patients, the recurrence rate was disappointingly high. Although the 2-year disease-specific survival rate was 37%, the DFS rate 2 years after inclusion was only 11%. Apparently, the high remission rate in our study does not convert to a proportional increase in the cure rate. In comparison, Turrisi et al31 have reported impressive survival data from a phase III study evaluating the efficacy of once-daily or twice-daily TRT concomitant with conventional EP chemotherapy in LD-SCLC. TRT was administered from the first chemotherapy cycle, and optimal chemotherapy doses during radiotherapy were stressed. In the hyperfractionated TRT arm, the 2-year overall and DFS rates were 47% and 29%, respectively. The authors concluded that four courses of EP plus TRT is an appropriate treatment in LD-SCLC. However, since systemic chemotherapy is considered the primary treatment strategy in LD-SCLC, there is still a definitive rationale for phase II and III trials implementing new promising anticancer agents in the hope of preventing the discouragingly high rate of chemoresistant relapses. Although we encountered one septic death (3%), our treatment regimen seemed to be well tolerated. Hematologic toxicity was the primary dose-limiting toxicity. Due to grade 3 to 4 hematologic toxicity, chemotherapy doses were reduced in 31% of all patients, and the fourth chemotherapy course (postradiotherapy) was delayed in 18%. Levitan et al25 and Gatzemeier et al24 reported a lower incidence of grade 3 to 4 hematotoxicity, most likely because of a lower paclitaxel dose and the use of G-CSF in Levitan et al and the lack of TRT in Gatzemeier et al. In two other phase II trials involving paclitaxel,26,28 the frequency of grade 3 and 4 hematologic toxicity was greater when compared with our data. This difference may, in the study by Hainsworth et al,28 be accounted for by the significantly larger doses of paclitaxel and platinum. In the study by Sandler et al,26 the higher toxicity was probably caused by the significantly larger radiotherapy dose administered concurrently with the third and fourth chemotherapy cycles. Although relatively infrequent and always reversible, nonhematologic toxicity was more frequent in our study when compared with the study by Levitan et al.25 However, Hainsworth et al28 and Ettinger et al27 reported significantly more grade 3 to 4 esophagitis (23% and 36%, respectively) when compared with our data (13%). In the former study, the greater toxicity was most likely related to the larger paclitaxel and platinum doses, whereas the slightly larger cisplatin dose and radiation intensity may have accounted for some of the increased esophagitis in the latter study. In contrast, Sandler et al26 reported only 3% grade 3 to 4 esophagitis from their study in which a total TRT dose of 63 Gy was administered. Moreover, Sandler et al26 reported more neurotoxicity than observed in the other phase II studies. The contributing neurotoxic effect of a larger cisplatin dose (80 mg/m2) in their study may have added significantly to the neurotoxicity incurred by paclitaxel. We have evaluated an effective paclitaxel-containing regimen for treatment of LD-SCLC. But despite the high response rates, the remission duration and survival outcomes were moderate. To justify the cost and toxicity of adding a third anticancer agent such as paclitaxel to the standard EP regimen and concurrent chest irradiation, survival improvement has to be proven in ongoing phase III trials.32-34
Supported by the Norwegian Cancer Society, Oslo, Norway.
We appreciate the secretarial assistance of Ann Grethe Nyheim at the Clinical Research Office, Troms
1. Sandler AB: Current management of small-cell lung cancer. Semin Oncol 24: 463-476, 1997[Medline]
2.
Kelly K: New chemotherapy agents for small-cell lung cancer. Chest 117: 156S-162S, 2000 (suppl 1)
3.
Evans WM, Shepard FA, Feld R, et al: VP-16 and cisplatin as first line-therapy for small-cell lung cancer. J Clin Oncol 3: 1471-1477, 1985 4. Evans WK, Osoba D, Feld R, et al: Etoposide (VP-16) and cisplatin: An effective treatment for relapse in small-cell lung cancer. J Clin Oncol 3: 65-71, 1985[Abstract] 5. Einhorn LH, Crawford J, Birch R, et al: Cisplatin plus etoposide consolidation following cyclophosphamide, doxorubicin and vincristine in limited small-cell lung cancer. J Clin Oncol 6: 451-456, 1988[Abstract] 6. Ettinger DS: Concurrent paclitaxel-containing regimens and thoracic radiation therapy for limited-disease small-cell lung cancer. Semin Radiat Oncol 9: 148-150, 1999 (suppl 1)[Medline]
7.
Johnson DH: Management of small-cell lung cancer: Current state of the art. Chest 116: 525S-530S, 1999 (suppl) 8. Pignon JP, Arriagada R, Ihde D, et al: A meta-analysis of thoracic radiotherapy for small-cell lung cancer. N Engl J Med 327: 1618-1624, 1992[Abstract] 9. Warde P, Payne D: Does thoracic irradiation improve survival and local control in limited-stage small-cell carcinoma of the lung? A meta-analysis. J Clin Oncol 10: 890-895, 1992[Abstract]
10.
Elias AD: Small cell lung cancer: State of the art in 1996. Chest 112: 251S-258S, 1997 (suppl) 11. Work E, Bentzen SM, Nielsen OS, et al: Prophylactic cranial irradiation in limited stage small-cell lung cancer: Survival benefit in patients with favorable characteristics. Eur J Cancer 32A: 772-778, 1996 12. Gregor A, Cull A, Stephens RJ, et al: Prophylactic cranial irradiation is indicated following complete response to induction therapy in small cell lung cancer: Result of a multicentre randomised trial. Eur J Cancer 33: 1752-1758, 1997
13.
Auperin A, Arriagada R, Pignon JP, et al: Prophylactic cranial irradiation for patients with small-cell lung cancer in complete remission. N Engl J Med 341: 476-484, 1999
14.
Arriagada R, Le Chevalier T, Borie F, et al: Prophylactic cranial irradiation for patients with small-cell lung cancer in complete remission. J Natl Cancer Inst 87: 183-190, 1995 15. Ettinger DS, Finkelstein DM, Sarma RP, et al: Phase II study of paclitaxel in patients with extensive-disease small-cell lung cancer: An Eastern Cooperative Oncology Group study. J Clin Oncol 13: 1430-1435, 1995[Abstract] 16. Kirschling RJ, Jung SH, Jett JR, et al: A phase II trial of Taxol and G-CSF in previously untreated patients with extensive-stage small-cell lung cancer. Proc Am Soc Clin Oncol 13: 326A, 1994 (abstr 1076) 17. Tishler RB, Schiff PB, Geard CR, et al: Taxol: A novel radiation sensitizer. Int J Radiat Oncol Biol Phys 22: 613-617, 1992[Medline]
18.
Liebmann J, Cook JA, Fisher J, et al: In vitro studies of Taxol as a radiation sensitizer in human tumor cells. J Natl Cancer Inst 86: 441-446, 1994
19.
Frei E III: Combination cancer chemotherapy: Presidential address. Cancer Res 32: 2593-2607, 1972 20. Evans WK, Feld R, Murray N, et al: Superiority of alternating non–cross-resistant chemotherapy in extensive small-cell lung cancer. Ann Intern Med 107: 451-458, 1987
21.
Fukuoka M, Furuse K, Saijo N, et al: Randomized trial of cyclophosphamide, doxorubicin, and vincristine versus cisplatin and etoposide versus alternation of these regimens in small-cell lung cancer. J Natl Cancer Inst 83: 855-861, 1991 22. Hainsworth JD, Stroup SL, Greco FA: Paclitaxel, carboplatin, and extended schedule etoposide in the treatment of small-cell lung carcinoma. Cancer 77: 2458-2463, 1996[Medline]
23.
Hainsworth JD, Gray JR, Stroup SL, et al: Paclitaxel, carboplatin, and extended schedule etoposide in the treatment of small-cell lung cancer: Comparison of sequential phase II trials using different dose intensities. J Clin Oncol 15: 3464-3470, 1997 24. Gatzemeier U, Jagos U, Kaukel E, et al: Paclitaxel, carboplatin, and oral etoposide: A phase II trial in limited-stage small-cell lung cancer. Semin Oncol 24: 149-152, 1997 (suppl 12)
25.
Levitan N, Dowlati A, Shina D, et al: Multi-institutional phase I/II trial of paclitaxel, cisplatin, and etoposide with concurrent radiation for limited-stage small-cell lung carcinoma. J Clin Oncol 18: 1102-1109, 2000 26. Sandler A, Declerk L Wagner H, et al: A phase II study of cisplatin (P) plus etoposide (E) plus paclitaxel (T) (PET) and concurrent radiation therapy for previously untreated limited stage small-cell lung cancer (SCLC) (E2596): An Eastern Cooperative Oncology Group trial. Proc Am Soc Clin Oncol 19: 491a, 2000 (abstr 1920) 27. Ettinger DS, Seiferheld WF, Abrams RA, et al: Cisplatin (P), etoposide (E), paclitaxel (P) and concurrent hyperfractionated thoracic radiotherapy (TRT) for patients (Pts) with limited disease (LD) small cell lung cancer (SCLC): Preliminary results of RTOG 96-09. Proc Am Soc Clin Oncol 19: 490a, 2000 (abstr 1917) 28. Hainsworth JD, Erland J, Peters M, et al: Treatment with small-cell lung cancer (SCLC) with Taxol (1-hour infusion), carboplatin, and etoposide: Phase II study of an outpatient regimen. Proc Am Soc Clin Oncol 13: 350, 1994 (abstr 1171) 29. Hainsworth JD, Miller P, Menchise A, et al: Treatment of locally advanced non–small-cell lung cancer with Taxol (1-hour infusion), cisplatin, etoposide, and radiation therapy (RT): A phase II trial. Lung Cancer 11: 182, 1994 (suppl 1, abstr) 30. Bunn PA, Kelly K: A phase I study of cisplatin, etoposide, and paclitaxel in small-cell lung cancer. Semin Oncol 24: 144-148, 1997 (suppl 12)
31.
Turrisi AT, Kim K, Blum R, et al: Twice-daily compared to once-daily thoracic radiotherapy in limited small-cell lung cancer treated concurrently with cisplatin and etoposide. N Engl J Med 340: 265-271, 1999 32. Birch R, Greco F, Hainsworth J, et al: Preliminary results of a randomized study comparing etoposide and carboplatin (EP) with or without paclitaxel (T) in newly diagnosed small-cell lung cancer. Proc Am Soc Clin Oncol 19: 490a, 2000 (abstr 1918) 33. Gatzemeier U, Faderl B, Macha H, et al: A phase III trial of Taxol, etoposide phosphate and carboplatin (TEC) versus carboplatin, etoposide phosphate and vincristine (CEV) in previously untreated small-cell lung cancer (SCLC). Lung Cancer 29: 29, 2000 (suppl 1, abstr) 34. Mavroudis D, Papadakis E, Veslemes M, et al: A multicenter randomized phase III study comparing paclitaxel-cisplatin-etoposide (TEP) versus cisplatin-etoposide (EP) as front-line treatment in patients with small-cell lung cancer (SCLC). Lung Cancer 29: 29, 2000 (suppl 1, abstr) Submitted November 15, 2000; accepted April 25, 2001.
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Copyright © 2001 by the American Society of Clinical Oncology, Online ISSN: 1527-7755. Print ISSN: 0732-183X
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ABSTRACT
INTRODUCTION
2.5 x 109/L, neutrophils 
