Dose Intensified Molecular Targeted Radiotherapy for Cancer-Lymphoma as a Paradigm

Gerald L Denardo, Sally DeNardo

Research output: Contribution to journalReview article

6 Citations (Scopus)

Abstract

Although most patients with locoregional cancer are cured by surgery, radiotherapy, chemotherapy, and combinations thereof, those with distant metastases are not despite systemic chemotherapy. These patients respond to local radiotherapy but generally need systemic therapy. Non-Hodgkin's lymphoma (NHL) provides a paradigm for the role of molecular targeted radiotherapy (MTRT) because these patients have multifocal disease in most cases. Although patients with NHL achieve remissions after multiple cycles of chemotherapy, less than one half of those with aggressive NHL are cured and almost none of those with low grade NHL. Furthermore, NHL, like other cancers, becomes chemoresistant, yet remains responsive to radiotherapy. MTRT, radiation targeted by molecules, is a good strategy for the treatment of multifocal and radiosensitive cancers. Radioimmunotherapy (RIT) is an MTRT approach using MAbs, or parts thereof, to target the radionuclide that delivers radiation. Two anti-CD20 monoclonal antibodies (MAbs), one labeled with 111In for imaging or 90Y for therapy and a second labeled with 131I for imaging and therapy, have proven effective and safe for MTRT for NHL patients. The importance of the radiation is demonstrated in the data from the randomized pivotal trial of 90Y-ibritumomab; response rates were distinctly better in the 90Y-ibritumomab arm than in the rituximab arm. Furthermore, the efficacy of 131I-tositumomab was greater than that of the same MAb alone in another pivotal trial. Although hematologic toxicity is dose limiting for MTRT, febrile neutropenia is uncommon. MTRT is also not associated with mucositis, hair loss, or persistent nausea or vomiting, unlike chemotherapy. Randomized trials of MTRT in different strategies have not been conducted, but there is evidence of better outcomes, particularly for strategies that provide dose intensification, such as pretargeted MTRT, multiple dosing ("fractionation"), and MTRT with stem cell transplantation (SCT). Pretargeted RIT separates delivery of the targeting molecule from radionuclide delivery, provides dose escalation, and is more effective than direct one-step RIT, although more complicated to implement. Improved drugs and strategies for MTRT have documented potential for better patient outcomes. Smaller radionuclide carriers, such as those used for pretargeted MTRT, should be incorporated into the management of patients with NHL and other cancers soon after the patients have proven incurable. Expected improvements using better drugs, strategies, and combinations with other drugs seem likely to make MTRT integral in the management of many patients with cancer and likely to lead to cures of NHL.

Original languageEnglish (US)
Pages (from-to)136-144
Number of pages9
JournalSeminars in Nuclear Medicine
Volume40
Issue number2
DOIs
StatePublished - Mar 2010

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Lymphoma
Radiotherapy
Non-Hodgkin's Lymphoma
Neoplasms
Radioimmunotherapy
Radioisotopes
Radiation
Drug Therapy
Monoclonal Antibodies
Febrile Neutropenia
Mucositis
Alopecia
Stem Cell Transplantation
Drug Combinations
Therapeutics
Combination Drug Therapy
Pharmaceutical Preparations
Nausea
Vomiting
Neoplasm Metastasis

ASJC Scopus subject areas

  • Radiology Nuclear Medicine and imaging

Cite this

Dose Intensified Molecular Targeted Radiotherapy for Cancer-Lymphoma as a Paradigm. / Denardo, Gerald L; DeNardo, Sally.

In: Seminars in Nuclear Medicine, Vol. 40, No. 2, 03.2010, p. 136-144.

Research output: Contribution to journalReview article

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