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Concurrent low-dose cisplatin and thoracic radiotherapy in patients with inoperable stage III non-small cell lung cancer: a phase II trial with special reference to the hemoglobin level as prognostic parameter

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Abstract

Purpose

To evaluate the efficacy of concurrent radiochemotherapy in patients with stage III non-small cell lung cancer (NSCLC), and to examine the effect of hemoglobin levels on survival of those patients. The negative impact of anemia on survival has been noticed for other cancer sites including the head and neck, and the uterine cervix, but it has been rarely described in NSCLC cancer patients treated with radiotherapy.

Methods

From April 1995 through March 2002, 56 patients with inoperable stage III non-small lung cancer were treated with radiotherapy consisting of 60 Gy (50 Gy+10 Gy boost) given in 30 fractions of 2 Gy daily, 5 days a week, over a period of 6 weeks, and concurrent low-dose daily chemotherapy (CHT) consisting of 6 mg/m2 of cisplatin given Mondays–Fridays during weeks 1–2 and 5–6. All patients had stage III disease and ages ranged from 39 to 81 years old (median 63.9 years).

Results

The 2-year and 3-year survival rates were 34% and 16%, respectively. Patients with a pretreatment hemoglobin level superior or equal to 11.6 g/dl had a 2-year survival rate of 52% as compared to 15.5% for patients with a pretreatment hemoglobin level inferior to 11.6 g/dl (p=0.0075). Patients with higher KI (>70%) showed better survival rates than those with lower KI. Surprisingly, patients in stage IIIA did not survive significantly longer than those in stage IIIB. Hematological toxicity (grade ≥2) prevailed (25%), followed by esophageal (5.4%) and bronchopulmonary (2%) toxicity. Only three patients experienced acute grade 3 hematological toxicity. Because of acute toxic effects, irradiation was interrupted in 8 patients (14.3%) for 7–13 days (median 7.5 days). Late high-grade (≥3) toxicity was not found. No grade 4 toxicity or treatment-related deaths were observed during this study.

Conclusion

Our data show that concurrent radiotherapy with daily low dose cisplatin is well tolerated, and shows survival rates comparable to more aggressive treatment regimens. A combination of this chemotherapy with accelerated hyperfractionated radiotherapy might improve the results in the future. Furthermore, we could show that the hemoglobin levels prior to therapy have an influence on the prognosis, where lower levels were associated with worse outcome. Further trials should consider supplementation with erythropoietin.

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References

  • Armstrong J, Raben A, Zelefsky M et al. (1997) Promising survival with three-dimensional conformal radiation therapy for non-small cell lung cancer. Radiother Oncol 44:17–22

    CAS  PubMed  Google Scholar 

  • Atagi S, Kawahara M, Ogawara M et al. (2000) Phase II trial of daily low-dose carboplatin and thoracic radiotherapy in elderly patients with locally advanced non-small cell lung cancer. Jpn J Clin Oncol 30:59–64

    Google Scholar 

  • Baumann M, Appold S, Petersen C, Zips D, Herrmann T (2001) Dose and fractionation concepts in the primary radiotherapy of non-small cell lung cancer. Lung Cancer 33 [Suppl 1]:S35–45

    Google Scholar 

  • Blackstock AW, Lesser GJ, Fletcher-Steede J et al. (2001) Phase I study of twice-weekly gemcitabine and concurrent thoracic radiation for patients with locally advanced non-small-cell lung cancer. Int J Radiat Oncol Biol Phys 51:1281–1289

    CAS  PubMed  Google Scholar 

  • Buccheri G, Ferrigno D (1996) Therapeutic options for regionally advanced non-small cell lung cancer. Lung Cancer 14:281–300

    CAS  PubMed  Google Scholar 

  • Bunn PA Jr (2001) Irinotecan and platinums in the treatment of non small-cell lung cancer. Clin Lung Cancer 2 [Suppl 2]:S14–19

  • Chevalier T Le, Arriagada R, Quoix E et al. (1991) Radiotherapy alone versus combined chemotherapy and radiotherapy in nonresectable non-small-cell lung cancer: first analysis of a randomized trial in 353 patients. J Natl Cancer Inst 83:417–423

    Article  CAS  PubMed  Google Scholar 

  • Choy H, DeVore RF, Hande KR et al. (2001a) Phase I trial of outpatient weekly docetaxel, carboplatin and concurrent thoracic radiation therapy for stage III unresectable non-small-cell lung cancer: a Vanderbilt cancer center affiliate network (VCCAN) trial. Lung Cancer 34:441–449

    CAS  PubMed  Google Scholar 

  • Choy H, Pyo H, Kim JS, MacRae R (2001b) Role of taxanes in the combined modality treatment of patients with locally advanced non-small cell lung cancer. Expert Opin Pharmacother 2:963–974

    Google Scholar 

  • Cox JD, Stetz J, Pajak TF (1995) Toxicity criteria of the Radiation Therapy Oncology Group (RTOG) and the European Organization for Research and Treatment of Cancer (EORTC). Int J Radiat Oncol Biol Phys 31:1341–1346

    CAS  PubMed  Google Scholar 

  • Crispo A, Brennan P, Jockel KH et al. (2004) The cumulative risk of lung cancer among current, ex- and never-smokers in European men. Br J Cancer 91:1280–1286

    CAS  PubMed  Google Scholar 

  • Daly T, Poulsen MG, Denham JW et al. (2003) The effect of anaemia on efficacy and normal tissue toxicity following radiotherapy for locally advanced squamous cell carcinoma of the head and neck. Radiother Oncol 68:113–122

    PubMed  Google Scholar 

  • Depierre A, Milleron B, Moro-Sibilot D et al. (2002) Preoperative chemotherapy followed by surgery compared with primary surgery in resectable stage I (except T1N0), II, and IIIa non-small-cell lung cancer. J Clin Oncol 20:247–253

    PubMed  Google Scholar 

  • Dillman RO, Seagren SL, Propert KJ et al. (1990) A randomized trial of induction chemotherapy plus high-dose radiation versus radiation alone in stage III non-small-cell lung cancer. N Engl J Med 323:940–945

    CAS  PubMed  Google Scholar 

  • Dunst J (2004) Erythropoietin and radiotherapy: a dangerous combination? Strahlenther Onkol 180:133–135

    PubMed  Google Scholar 

  • Dunst J, Kuhnt T, Strauss HG, Krause U, Pelz T, Koelbl H, Haensgen G (2003) Anemia in cervical cancers: impact on survival, patterns of relapse, and association with hypoxia and angiogenesis. Int J Radiat Oncol Biol Phys 56:778–787

    PubMed  Google Scholar 

  • Ginsberg RJ (1995) Neoadjuvant (induction) treatment for non-small cell lung cancer. Lung Cancer 12 [Suppl 2]:S33–40

    Google Scholar 

  • Hazuka MB, Crowley JJ, Bunn PA Jr, O’Rourke M, Braun TJ, Livingston RB (1994) Daily low-dose cisplatin plus concurrent high-dose thoracic irradiation in locally advanced unresectable non-small-cell lung cancer: results of a phase II Southwest Oncology Group study. J Clin Oncol 12:1814–1820

    Google Scholar 

  • Henke M, Laszig R, Rube C et al. (2003) Erythropoietin to treat head and neck cancer patients with anaemia undergoing radiotherapy: randomised, double-blind, placebo-controlled trial. Lancet 362:1255–1260

    Article  CAS  PubMed  Google Scholar 

  • Jeremic B, Shibamoto Y (1996) Effect of interfraction interval in hyperfractionated radiotherapy with or without concurrent chemotherapy for stage III nonsmall cell lung cancer. Int J Radiat Oncol Biol Phys 34:303–308

    CAS  PubMed  Google Scholar 

  • Jeremic B, Shibamoto Y, Acimovic L, Djuric L (1995) Randomized trial of hyperfractionated radiation therapy with or without concurrent chemotherapy for stage III non-small-cell lung cancer. J Clin Oncol 13:452–458

    Google Scholar 

  • Kiura K, Ueoka H, Segawa Y et al. (2003) Phase I/II study of docetaxel and cisplatin with concurrent thoracic radiation therapy for locally advanced non-small-cell lung cancer. Br J Cancer 89:795–802

    CAS  PubMed  Google Scholar 

  • Langer CJ, Hirsch FR, Cortes-Funes H, Sawyer ST, Thatcher N (2003) Targeted molecular mechanisms of epoetin alfa. Lung Cancer 41 [Suppl 1]:S133–145

    Google Scholar 

  • MacRae R, Shyr Y, Johnson D, Choy H (2002) Declining hemoglobin during chemoradiotherapy for locally advanced non-small cell lung cancer is significant. Radiother Oncol 64:37–40

    CAS  PubMed  Google Scholar 

  • Non-small Cell Lung Cancer Collaborative Group (1995) Chemotherapy in non-small cell lung cancer: a meta-analysis using updated data on individual patients from 52 randomised clinical trials. BMJ 311:899–909

    PubMed  Google Scholar 

  • Obermair A, Cheuk R, Horwood K et al. (2001) Impact of hemoglobin levels before and during concurrent chemoradiotherapy on the response of treatment in patients with cervical carcinoma: preliminary results. Cancer 92:903–908

    CAS  PubMed  Google Scholar 

  • Perez CA, Pajak TF, Rubin P et al. (1987) Long-term observations of the patterns of failure in patients with unresectable non-oat cell carcinoma of the lung treated with definitive radiotherapy. Report by the Radiation Therapy Oncology Group. Cancer 59:1874–1881

    CAS  PubMed  Google Scholar 

  • Pisch J, Moskovitz T, Esik O, Homel P, Keller S (2002) Concurrent paclitaxel-cisplatin and twice-a-day irradiation in stage IIIA and IIIB NSCLC shows improvement in local control and survival with acceptable hematologic toxicity. Pathol Oncol Res 8:163–169

    CAS  PubMed  Google Scholar 

  • Pritchard RS, Anthony SP (1996) Chemotherapy plus radiotherapy compared with radiotherapy alone in the treatment of locally advanced, unresectable, non-small-cell lung cancer. A meta-analysis. Ann Intern Med 125:723–729

    CAS  PubMed  Google Scholar 

  • Rakovitch E, Tsao M, Ung Y, Pignol JP, Cheung P, Chow E (2004) Comparison of the efficacy and acute toxicity of weekly versus daily chemoradiotherapy for non-small-cell lung cancer: a meta-analysis. Int J Radiat Oncol Biol Phys 58:196–203

    PubMed  Google Scholar 

  • Rosell R, Gomez-Codina J, Camps C et al. (1994) A randomized trial comparing preoperative chemotherapy plus surgery with surgery alone in patients with non-small-cell lung cancer. N Engl J Med 330:153–158

    CAS  PubMed  Google Scholar 

  • Roth JA, Atkinson EN, Fossella F et al. (1998) Long-term follow-up of patients enrolled in a randomized trial comparing perioperative chemotherapy and surgery with surgery alone in resectable stage IIIA non-small-cell lung cancer. Lung Cancer 21:1–6

    Google Scholar 

  • Sause WT, Scott C, Taylor S et al. (1995) Radiation Therapy Oncology Group (RTOG) 88-08 and Eastern Cooperative Oncology Group (ECOG) 4588: preliminary results of a phase III trial in regionally advanced, unresectable non-small-cell lung cancer. J Natl Cancer Inst 87:198–205

    CAS  PubMed  Google Scholar 

  • Schaake-Koning C, Bogaert W van den, Dalesio O et al. (1992) Effects of concomitant cisplatin and radiotherapy on inoperable non-small-cell lung cancer. N Engl J Med 326:524–530

    CAS  PubMed  Google Scholar 

  • Segawa Y, Ueoka H, Kiura K et al. (2000) A phase II study of cisplatin and 5-fluorouracil with concurrent hyperfractionated thoracic radiation for locally advanced non-small-cell lung cancer: a preliminary report from the Okayama Lung Cancer Study Group. Br J Cancer 82:104–111

    CAS  PubMed  Google Scholar 

  • Sibley GS, Mundt AJ, Shapiro C, Jacobs R, Chen G, Weichselbaum R, Vijayakumar S (1995) The treatment of stage III nonsmall cell lung cancer using high dose conformal radiotherapy. Int J Radiat Oncol Biol Phys 33:1001–1007

    CAS  PubMed  Google Scholar 

  • Simon GR, Bunn PA Jr (2003) Taxanes in the treatment of advanced (stage III and IV) non-small cell lung cancer (NSCLC): recent developments. Cancer Invest 21:87–104

    Article  CAS  PubMed  Google Scholar 

  • Staar S, Rudat V, Stuetzer H et al. (2001) Intensified hyperfractionated accelerated radiotherapy limits the additional benefit of simultaneous chemotherapy—results of a multicentric randomized German trial in advanced head-and-neck cancer. Int J Radiat Oncol Biol Phys 50:1161–1171

    CAS  PubMed  Google Scholar 

  • Stadler P, Becker A, Feldmann HJ, Hansgen G, Dunst J, Wurschmidt F, Molls M (1999) Influence of the hypoxic subvolume on the survival of patients with head and neck cancer. Int J Radiat Oncol Biol Phys 44:749–754

    CAS  PubMed  Google Scholar 

  • Taylor NA, Liao ZX, Cox JD et al. (2004) Equivalent outcome of patients with clinical stage IIIA non-small-cell lung cancer treated with concurrent chemoradiation compared with induction chemotherapy followed by surgical resection. Int J Radiat Oncol Biol Phys 58:204–212

    PubMed  Google Scholar 

  • Vokes EE, Choy H (2003) Targeted therapies for stage III non-small cell lung cancer: integration in the combined modality setting. Lung Cancer 41 [Suppl 1]:S115–121

    Google Scholar 

  • Vokes EE, Herndon JE 2nd, Crawford J et al. (2002) 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

    CAS  PubMed  Google Scholar 

  • Werner-Wasik M, Scott C, Cox JD et al. (2000) Recursive partitioning analysis of 1999 Radiation Therapy Oncology Group (RTOG) patients with locally-advanced non-small-cell lung cancer (LA-NSCLC): identification of five groups with different survival. Int J Radiat Oncol Biol Phys 48:1475–1482

    CAS  PubMed  Google Scholar 

  • Wigren T (1997) Confirmation of a prognostic index for patients with inoperable non-small cell lung cancer. Radiother Oncol 44:9–15

    CAS  PubMed  Google Scholar 

  • Yamada M, Kudoh S, Fukuda H et al. (2002) Dose-escalation study of weekly irinotecan and daily carboplatin with concurrent thoracic radiotherapy for unresectable stage III non-small cell lung cancer. Br J Cancer 87:258–263

    CAS  PubMed  Google Scholar 

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Pradier, O., Lederer, K., Hille, A. et al. Concurrent low-dose cisplatin and thoracic radiotherapy in patients with inoperable stage III non-small cell lung cancer: a phase II trial with special reference to the hemoglobin level as prognostic parameter. J Cancer Res Clin Oncol 131, 261–269 (2005). https://doi.org/10.1007/s00432-004-0633-0

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  • DOI: https://doi.org/10.1007/s00432-004-0633-0

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