Skip to main content
NCBI home page
British Journal of Cancer logoLink to British Journal of Cancer
. 1993 Jun;67(6):1385–1390. doi: 10.1038/bjc.1993.256

A randomised study of bolus vs continuous pump infusion of ifosfamide and doxorubicin with oral etoposide for small cell lung cancer.

H Anderson 1, P Hopwood 1, J Prendiville 1, J A Radford 1, N Thatcher 1, L Ashcroft 1
PMCID: PMC1968524  PMID: 8390287

Abstract

One hundred and fifty-nine previously untreated patients with small cell lung cancer (SCLC), who were not eligible for intensive chemotherapy, were entered into a randomised study of intravenous (i.v.) doxorubicin and ifosfamide (with mesna) and oral etoposide. The i.v. drugs were given either by bolus therapy or by a continuous infusion (CI) pump over 7 days via a central venous line. Therapy was given for 6 weeks only. On weeks 1, 3 and 5 IV doxorubicin 35 mg m-2 was given with 5 days of oral etoposide 100 mg m-2 daily. On weeks 2, 4 and 6 IV ifosfamide 5 g m-2 was given with equidose mesna. The overall median survival was 25 weeks for patients in the bolus arm and 30 weeks for the CI therapy (P = 0.45). The overall response rate was 64% (18% complete response-CR) and 69% (30% CR) respectively (P = 0.13). The median WHO score for haematological toxicity was 4 for bolus therapy and 3 for CI therapy (P = 0.0007). Despite a trend for less supportive care for patients on CI therapy there were no significant differences in the use of i.v. antibodies and blood or platelet transfusions. There were fewer treatment delays due to myelotoxicity in the CI arm (P = 0.04). The median WHO score for non-haematological toxicity was 2 in both treatment groups. There was significantly less nausea (P = 0.037) but more mucositis (P = 0.01) in the CI arm. Weekly chemotherapy using CI treatment was as effective as bolus therapy. It was well accepted by patients. The assessment of quality of life in a subgroup of patients showed a statistically significant reduction in anxiety and depression for both groups of patients during therapy.

Full text

PDF
1385

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Anderson H., Lind M. J., Thatcher N., Swindell R., Woodcock A., Carroll K. B. Therapy for poor-risk patients with small-cell lung cancer using bolus ifosfamide and oral etoposide. Cancer Chemother Pharmacol. 1990;26(1):71–74. doi: 10.1007/BF02940299. [DOI] [PubMed] [Google Scholar]
  2. Blackledge G., Bush H., Chang J., Crowther D., Deakin D. P., Dodge O. G., Garrett J. V., Palmer M., Pearson D., Scarffe J. H. Intensive combination chemotherapy with vincristine, adriamycin and prednisolone (VAP) in the treatment of diffuse histology non-Hodgkin's lymphoma. (A report of 89 cases with extensive disease from the Manchester Lymphoma Group). Eur J Cancer. 1980 Nov;16(11):1459–1468. doi: 10.1016/0014-2964(80)90056-0. [DOI] [PubMed] [Google Scholar]
  3. Bosanquet A. G. Stability of solutions of antineoplastic agents during preparation and storage for in vitro assays. General considerations, the nitrosoureas and alkylating agents. Cancer Chemother Pharmacol. 1985;14(2):83–95. doi: 10.1007/BF00434343. [DOI] [PubMed] [Google Scholar]
  4. Brade W. P., Herdrich K., Varini M. Ifosfamide--pharmacology, safety and therapeutic potential. Cancer Treat Rev. 1985 Mar;12(1):1–47. doi: 10.1016/0305-7372(85)90011-8. [DOI] [PubMed] [Google Scholar]
  5. Cerny T., Blair V., Anderson H., Bramwell V., Thatcher N. Pretreatment prognostic factors and scoring system in 407 small-cell lung cancer patients. Int J Cancer. 1987 Feb 15;39(2):146–149. doi: 10.1002/ijc.2910390204. [DOI] [PubMed] [Google Scholar]
  6. Coates A., Gebski V., Bishop J. F., Jeal P. N., Woods R. L., Snyder R., Tattersall M. H., Byrne M., Harvey V., Gill G. Improving the quality of life during chemotherapy for advanced breast cancer. A comparison of intermittent and continuous treatment strategies. N Engl J Med. 1987 Dec 10;317(24):1490–1495. doi: 10.1056/NEJM198712103172402. [DOI] [PubMed] [Google Scholar]
  7. Controlled trial of twelve versus six courses of chemotherapy in the treatment of small-cell lung cancer. Report to the Medical Research Council by its Lung Cancer Working Party. Br J Cancer. 1989 Apr;59(4):584–590. doi: 10.1038/bjc.1989.118. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Earl H. M., Rudd R. M., Spiro S. G., Ash C. M., James L. E., Law C. S., Tobias J. S., Harper P. G., Geddes D. M., Eraut D. A randomised trial of planned versus as required chemotherapy in small cell lung cancer: a Cancer Research Campaign trial. Br J Cancer. 1991 Sep;64(3):566–572. doi: 10.1038/bjc.1991.351. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Hopwood P., Thatcher N. Current status of quality of life measurement in lung cancer patients. Oncology (Williston Park) 1991 May;5(5):159-166; discussion 166, 169, 173. [PubMed] [Google Scholar]
  10. Hopwood P., Thatcher N. Preliminary experience with quality of life evaluation in patients with lung cancer. Oncology (Williston Park) 1990 May;4(5):158–171. [PubMed] [Google Scholar]
  11. Issell B. F. The podophyllotoxin derivatives VP16-213 and VM26. Cancer Chemother Pharmacol. 1982;7(2-3):73–80. doi: 10.1007/BF00254525. [DOI] [PubMed] [Google Scholar]
  12. Kamthan A. G., Lind M. J., Thatcher N., Steward W. P., Bronchud M. H., Ranson M. R., Stout R. Ifosfamide, doxorubicin and etoposide in small cell lung cancer patients with poor prognosis. Eur J Cancer. 1990;26(6):691–694. doi: 10.1016/0277-5379(90)90118-d. [DOI] [PubMed] [Google Scholar]
  13. Klimo P., Connors J. M. MACOP-B chemotherapy for the treatment of diffuse large-cell lymphoma. Ann Intern Med. 1985 May;102(5):596–602. doi: 10.7326/0003-4819-102-5-596. [DOI] [PubMed] [Google Scholar]
  14. Maguire P., Selby P. Assessing quality of life in cancer patients. Br J Cancer. 1989 Sep;60(3):437–440. doi: 10.1038/bjc.1989.301. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Miles D. W., Earl H. M., Souhami R. L., Harper P. G., Rudd R., Ash C. M., James L., Trask C. W., Tobias J. S., Spiro S. G. Intensive weekly chemotherapy for good-prognosis patients with small-cell lung cancer. J Clin Oncol. 1991 Feb;9(2):280–285. doi: 10.1200/JCO.1991.9.2.280. [DOI] [PubMed] [Google Scholar]
  16. Miller A. B., Hoogstraten B., Staquet M., Winkler A. Reporting results of cancer treatment. Cancer. 1981 Jan 1;47(1):207–214. doi: 10.1002/1097-0142(19810101)47:1<207::aid-cncr2820470134>3.0.co;2-6. [DOI] [PubMed] [Google Scholar]
  17. Morstyn G., Ihde D. C., Lichter A. S., Bunn P. A., Carney D. N., Glatstein E., Minna J. D. Small cell lung cancer 1973-1983: early progress and recent obstacles. Int J Radiat Oncol Biol Phys. 1984 Apr;10(4):515–539. doi: 10.1016/0360-3016(84)90032-4. [DOI] [PubMed] [Google Scholar]
  18. Murray N., Shah A., Osoba D., Page R., Karsai H., Grafton C., Goddard K., Fairey R., Voss N. Intensive weekly chemotherapy for the treatment of extensive-stage small-cell lung cancer. J Clin Oncol. 1991 Sep;9(9):1632–1638. doi: 10.1200/JCO.1991.9.9.1632. [DOI] [PubMed] [Google Scholar]
  19. Radford J. A., Margison J. M., Swindell R., Lind M. J., Wilkinson P. M., Thatcher N. The stability of ifosfamide in aqueous solution and its suitability for continuous 7-day infusion by ambulatory pump. Cancer Chemother Pharmacol. 1990;26(2):144–146. doi: 10.1007/BF02897261. [DOI] [PubMed] [Google Scholar]
  20. Richards M. A., Hopwood P., Ramirez A. J., Twelves C. J., Ferguson J., Gregory W. M., Swindell R., Scrivener W., Miller J., Howell A. Doxorubicin in advanced breast cancer: influence of schedule on response, survival and quality of life. Eur J Cancer. 1992;28A(6-7):1023–1028. doi: 10.1016/0959-8049(92)90447-a. [DOI] [PubMed] [Google Scholar]
  21. Spiro S. G., Souhami R. L., Geddes D. M., Ash C. M., Quinn H., Harper P. G., Tobias J. S., Partridge M., Eraut D. Duration of chemotherapy in small cell lung cancer: a Cancer Research Campaign trial. Br J Cancer. 1989 Apr;59(4):578–583. doi: 10.1038/bjc.1989.117. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. Tannock I. F., Boyd N. F., DeBoer G., Erlichman C., Fine S., Larocque G., Mayers C., Perrault D., Sutherland H. A randomized trial of two dose levels of cyclophosphamide, methotrexate, and fluorouracil chemotherapy for patients with metastatic breast cancer. J Clin Oncol. 1988 Sep;6(9):1377–1387. doi: 10.1200/JCO.1988.6.9.1377. [DOI] [PubMed] [Google Scholar]
  23. Taylor C. W., Crowley J., Williamson S. K., Miller T. P., Taylor S. A., Giri T. G., Stephens R. L., Livingston R. B. Treatment of small-cell lung cancer with an alternating chemotherapy regimen given at weekly intervals: a Southwest Oncology Group pilot study. J Clin Oncol. 1990 Nov;8(11):1811–1817. doi: 10.1200/JCO.1990.8.11.1811. [DOI] [PubMed] [Google Scholar]
  24. Thatcher N., Barber P. V., Hunter R. D., Carroll K. B., Jegarajah S., Wilkinson P. M., Crowther D. 11-week course of sequential methotrexate, thoracic irradiation, and moderate-dose cyclophosphamide for "limited"-stage small-cell bronchogenic carcinoma. A study from the Manchester Lung Tumour Group. Lancet. 1982 May 8;1(8280):1040–1043. doi: 10.1016/s0140-6736(82)92099-2. [DOI] [PubMed] [Google Scholar]
  25. Thatcher N., James R. D., Steward W. P., Barber P. V., Feinmann D., Lawson B. A., Carroll K. B. Three months' treatment with cyclophosphamide, VP-16-213 followed by methotrexate and thoracic radiotherapy for small cell lung cancer. Cancer. 1985 Sep 15;56(6):1332–1336. doi: 10.1002/1097-0142(19850915)56:6<1332::aid-cncr2820560619>3.0.co;2-e. [DOI] [PubMed] [Google Scholar]
  26. Vogelzang N. J. Continuous infusion chemotherapy: a critical review. J Clin Oncol. 1984 Nov;2(11):1289–1304. doi: 10.1200/JCO.1984.2.11.1289. [DOI] [PubMed] [Google Scholar]
  27. Workman P. Infusional anthracyclines: is slower better? If so, why? Ann Oncol. 1992 Sep;3(8):591–594. [PubMed] [Google Scholar]
  28. Zigmond A. S., Snaith R. P. The hospital anxiety and depression scale. Acta Psychiatr Scand. 1983 Jun;67(6):361–370. doi: 10.1111/j.1600-0447.1983.tb09716.x. [DOI] [PubMed] [Google Scholar]
  29. de Haes J. C., van Knippenberg F. C., Neijt J. P. Measuring psychological and physical distress in cancer patients: structure and application of the Rotterdam Symptom Checklist. Br J Cancer. 1990 Dec;62(6):1034–1038. doi: 10.1038/bjc.1990.434. [DOI] [PMC free article] [PubMed] [Google Scholar]

Articles from British Journal of Cancer are provided here courtesy of Cancer Research UK

RESOURCES