Chemotherapy Combined with Radionuclide Therapy

Part of the Medical Radiology book series (MEDRAD)


Virtually no malignancies have been cured by using single modalities of treatment. The evolution of tumour-targeted radionuclide therapies such as radioimmunotherapy and radiopeptide therapy provides a synergistic complement to conventional chemotherapy of cancer. In addition, the advent of biological agents which interfere with tumour metabolic pathways offers an exciting prospect of combination radionuclide—chemo biological therapy to enhance efficacy and minimise toxicity. The formal clinical trial evaluation of such evolving multimodality therapy of cancer is described to facilitate valid demonstration of efficacy and safety and to provide the level of evidence required for adoption into routine oncology clinical practice.


Maximum Tolerable Dose Objective Response Rate Radionuclide Therapy Historical Control Group Hormone Refractory Prostate Cancer 


  1. Barton S (2000) Which clinical studies provide the best evidence. Br Med J 321:255–256CrossRefGoogle Scholar
  2. Ben-Josef E (2007) Capecitabine and radiotherapy as neo-adjuvant treatment for rectal cancer. Am J Clin Oncol 30:649–655PubMedCrossRefGoogle Scholar
  3. Benson K, Hartz AJ (2000) A comparison of observational and randomised controlled trials. N Engl J Med 342:1878–1886PubMedCrossRefGoogle Scholar
  4. Cescato R et al (2008) Bombesin receptor antagonists may be preferable to agonists for tumour targeting. J Nucl Med 49:318–326PubMedCrossRefGoogle Scholar
  5. Claringbold PG et al (2011) Phase II study of radiopeptide 177Lu-octreotate and capecitabine therapy of progressive disseminated neuroendocrine tumours. Eur J Nucl Med Mol Imaging 38:302–311PubMedCrossRefGoogle Scholar
  6. Department of Health and Human Services. (2005) Protection of human subjects: informed consent. Washington. Federal Register, June 23rd Part 46.116Google Scholar
  7. Eisenhauer EA (2009) New response evaluation criteria in solid tumours: Revised RECIST guideline (version 1.1). Eur J Cancer 45:228–247PubMedCrossRefGoogle Scholar
  8. Evens AM et al (2009) The novel expanded porphyrin, motexafin gadolinium, combined with 90Y-ibritumomab tiuxetan for relapsed/refractory non- Hodgkin’s lymphoma: oreclinical findings and results of a Phase I trial. Clin Cancer Res 15:6462–6471PubMedCentralPubMedCrossRefGoogle Scholar
  9. Ferrigro D, Bucchesi G (1994) Karnofsky and ECOG performance status in lung cancer: equivalence, construct validity, and predictive validity. In: Proceedings, annual meeting of the American Society of Clinical Oncology, vol 13, p 326Google Scholar
  10. Fleming TR (1982) One sample multiple testing procedure for Phase II clinical trials. Biometrics 38:143–151PubMedCrossRefGoogle Scholar
  11. Gehan EA (1961) The determination of the number of patients required in a preliminary and follow-up trial of a new chemotherapeutic agent. J Chron Dis 13:346–353PubMedCrossRefGoogle Scholar
  12. Glynne-Jones R et al (2006) The integration of oral capecitabine into chemoradiation regimens for locally advanced rectal cancer. Ann Oncol 17(3):361–371PubMedCrossRefGoogle Scholar
  13. Herbertson R et al (2009) Targeted chemoradiation in metastatic colorectal cancer. A phase I trial of 131I-Hu A33 with concurrent capecitabine EANM Congress OP 531Google Scholar
  14. Hubble D et al (2010) 177Lu-octreotate, alone or with radiosensitising chemotherapy, is safe in neuroendocrine tumour patients previously treated with high-activity 111In-octreotide. Eur J Nucl Med Mol Imaging 37:1869–1875PubMedCrossRefGoogle Scholar
  15. Kapadia NS et al (2008) In vitro evaluation of radioprotective and radiosensitizing effects of rituximab. J Nucl Med 49(4):674–678PubMedCrossRefGoogle Scholar
  16. Kleinbaum DG, (1994) Logistic regression. A self-learning text. Springer, New YorkGoogle Scholar
  17. Kleinbaum DG, (1996) Survival analysis. A self-learning text. Springer, New YorkGoogle Scholar
  18. Kong G et al (2009) High-administered activity in-111 octreotide therapy with concomitant radiosensitising 5-FU chemotherapy for treatment of neuroendocrine tumours. Cancer Bio Radiopharm 24(5):527–533CrossRefGoogle Scholar
  19. Kvols MD (2005) Radiation sensitizers: a selective review of molecules targeting DNA and non-DNA targets. J Nucl Med 46 (suppl 1):87S–190SGoogle Scholar
  20. Lam GEHM et al (2009) 188Re-HEDP combined with capecitabine in hormone-refractory prostate cancer patients with bone metastases: a phase I safety and toxicity study. Eur J Nucl Med Mol Imaging 36:1425–1433PubMedCentralPubMedCrossRefGoogle Scholar
  21. Lam MGEH, Zonnenberg BA (2008) Multimodality treatment in hormone refractory prostate cancer patients with bone metastases. Eur J Nucl Med Mol Imaging 35:1394–1395PubMedCentralCrossRefGoogle Scholar
  22. Lawrence TS et al (1997) Fluoropyrimidine—radiation interactions in cells and tumours. Semin Rad Oncol 4:260–266CrossRefGoogle Scholar
  23. Maddalena ME et al (2009) 177Lu-AMBA biodistribution radiotherapeutic efficacy, imaging and antoradiography in prostate cancer models with low GRP-R expression. J Nucl Med 50:2017–2024PubMedCrossRefGoogle Scholar
  24. Perry M (ed) (1997) The chemotherapy source book, 2nd edn. Williams and Wilkins, Baltimore, p 21Google Scholar
  25. Rodel C (2008) Radiation therapy combined with novel chemotherapy regimens and targeted agents for patients with rectal cancer. ASCO Educational BookGoogle Scholar
  26. Sciuto R et al (2002) Effects of low-dose cisplatin on 89Sr therapy for painful bone metastases from prostate cancer. A randomised clinical trial. J Nucl Med 43:79–86PubMedGoogle Scholar
  27. Shibata S et al (2009) A Phase I study of a combination of 90Y-anti CEA antibody and gemcitabine in patients with CEA-producing advanced malignancies. Clin Cancer Res 18:2935–2941CrossRefGoogle Scholar
  28. Simon R (1986) Confidence intervals for reporting clinical trial results. Ann Int Med 105:4429–4435Google Scholar
  29. Simon R (1989) Optimal two-stage designs for Phase II clinical trials. Control Clin Trials 10:1–10PubMedCrossRefGoogle Scholar
  30. Sivridis E et al (2002) Thymidine phosphorylase expression in normal hyperplastic and neoplastic prostates. Br J Cancer 86:1465–1471PubMedCentralPubMedCrossRefGoogle Scholar
  31. Strosberg J et al. (2011) First-line chemotherapy with capecitabine and temozolomide in patients with metastatic pancreatic endocrine carcinomas. Cancer 117:268–275Google Scholar
  32. van Essen M et al (2008) Report on short term side effects of treatments with 177Lu-octreotate in combination with capecitabine in seven patients with GEP neuroendocrine tumours. Eur J Nucl Med Mol Imaging 35(4):743–748PubMedCentralPubMedCrossRefGoogle Scholar
  33. Van Poppel H (2005) Recent docetaxel studies establish a new standard of care in hormone refractory prostate cancer. Can J Urol. Suppl 1:81–85Google Scholar
  34. Walko CM, Lindley C (2005) Capecitabine: a review. Clin Ther 27:23–44PubMedCrossRefGoogle Scholar
  35. Wittes RE, Leventhal BG (eds) (1988) Statistical methods in clinical oncology. New York, Raven PressGoogle Scholar
  36. Wong JYC et al (2003) A Phase I trial of 90Y-anti CEA chimeric T84.66 radioimmunotherapy with 5-FU in patients with metastatic colorectal cancer. Clin Cancer Res 9:5842–5852PubMedGoogle Scholar
  37. Yao JC et al (2008a) Targeting vascular endothelial growth factor in advanced carcinoid tumor: a random assignment phase II study of depot octreotide with bevacizumab and pegylated interferon alfa-2b. J Clin Oncol 26:1316–1323PubMedCrossRefGoogle Scholar
  38. Yao JC et al (2008b) Efficacy of RAD 001 (Everolimus) and Octreotate LAR in advanced low t o intermediate grade NETs. Results of a Phase II study. J Clin Oncol 26:4311–4318PubMedCentralPubMedCrossRefGoogle Scholar

Copyright information

© Springer-Verlag Berlin Heidelberg 2012

Authors and Affiliations

  1. 1.Department of OncologyFremantle hospitalFremantleAustralia
  2. 2.Department of Nuclear MedicineSchool of Medicine and Pharmacology, Fremantle Hospital, The University of Western AustraliaFremantleAustralia

Personalised recommendations