Intraperitoneal radioimmunochemotherapy of ovarian cancer

A phase I study

Ruby F. Meredith, Ronald D. Alvarez, Edward E. Partridge, M. B. Khazaeli, Chin Yu Lin, Daniel J. Macey, J. Maxwell Austin, Larry Kilgore, William E. Grizzle, Jeffrey Schlom, Albert F. Lobuglio

Research output: Contribution to journalArticle

73 Citations (Scopus)

Abstract

A phase I trial was designed to examine the feasibility of combining interferon and Taxol with intraperitoneal radioimmunotherapy (177Lu-CC49). Patients with recurrent or persistent ovarian cancer confined to the abdominal cavity after first line therapy, Karnofsky performance status >60, adequate liver, renal and hematologic function, and tumor that reacted with CC49 antibody were enrolled. Human recombinant alpha interferon (IFN) was administered as 4 subcutaneous injections of 3 × 106U on alternate days beginning 5 days before RIT to increase the expression of the tumor-associated antigen, TAG-72. The addition of IFN increased hematologic toxicity such that the maximum tolerated dose (MTD) of the combination was 40 mCi/m2compared to 177Lu-CC49 alone (45 mCi/m2). Taxol, which has radiosensitizing effects as well as antitumor activity against ovarian cancer, was given intraperitoneally (IP) 48 hrs before RIT. It was initiated at 25 mg/m2and escalated at 25 mg/m2increments to 100 mg/m2Subsequent groups of patients were treated with IFN + 100 mg/m2Taxol + escalating doses of 177Lu-CC49. Three or more patients were treated in each dose group and 34 patients were treated with the 3-agent combination. Therapy was well tolerated with the expected reversible hematologic toxicity. The MTD for 177Lu-CC49 was 40 mCi/m2when given with IFN + 100 mg/m2Taxol. Interferon increased the effective whole body half-time of radioactivity and the whole body radiation dose. Taxol did not have a significant effect on pharmacokinetic or dosimetry parameters. Four of 17 patients with CT measurable disease had a partial response (PR) and 4 of 27 patients with non-measurable disease have progression-free intervals of 18+, 21+, 21+, and 37+ months. The combination of intraperitoneal Taxol chemotherapy (100 mg/m2) with RIT using 177Lu-CC49 and interferon was well tolerated, with bone marrow suppression as the dose-limiting toxicity.

Original languageEnglish (US)
Pages (from-to)305-315
Number of pages11
JournalCancer Biotherapy and Radiopharmaceuticals
Volume16
Issue number4
DOIs
StatePublished - Aug 1 2001

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Ovarian Neoplasms
Interferons
Paclitaxel
Maximum Tolerated Dose
Radiation-Sensitizing Agents
Radioimmunotherapy
Karnofsky Performance Status
Abdominal Cavity
Whole-Body Irradiation
Subcutaneous Injections
Interferon-alpha
Radioactivity
Disease Progression
Pharmacokinetics
Bone Marrow
Kidney
Drug Therapy
Liver
Therapeutics
Neoplasms

All Science Journal Classification (ASJC) codes

  • Oncology
  • Radiology Nuclear Medicine and imaging
  • Pharmacology
  • Cancer Research

Cite this

Meredith, R. F., Alvarez, R. D., Partridge, E. E., Khazaeli, M. B., Lin, C. Y., Macey, D. J., ... Lobuglio, A. F. (2001). Intraperitoneal radioimmunochemotherapy of ovarian cancer: A phase I study. Cancer Biotherapy and Radiopharmaceuticals, 16(4), 305-315. https://doi.org/10.1089/108497801753131381

Intraperitoneal radioimmunochemotherapy of ovarian cancer : A phase I study. / Meredith, Ruby F.; Alvarez, Ronald D.; Partridge, Edward E.; Khazaeli, M. B.; Lin, Chin Yu; Macey, Daniel J.; Austin, J. Maxwell; Kilgore, Larry; Grizzle, William E.; Schlom, Jeffrey; Lobuglio, Albert F.

In: Cancer Biotherapy and Radiopharmaceuticals, Vol. 16, No. 4, 01.08.2001, p. 305-315.

Research output: Contribution to journalArticle

Meredith, RF, Alvarez, RD, Partridge, EE, Khazaeli, MB, Lin, CY, Macey, DJ, Austin, JM, Kilgore, L, Grizzle, WE, Schlom, J & Lobuglio, AF 2001, 'Intraperitoneal radioimmunochemotherapy of ovarian cancer: A phase I study', Cancer Biotherapy and Radiopharmaceuticals, vol. 16, no. 4, pp. 305-315. https://doi.org/10.1089/108497801753131381
Meredith RF, Alvarez RD, Partridge EE, Khazaeli MB, Lin CY, Macey DJ et al. Intraperitoneal radioimmunochemotherapy of ovarian cancer: A phase I study. Cancer Biotherapy and Radiopharmaceuticals. 2001 Aug 1;16(4):305-315. https://doi.org/10.1089/108497801753131381
Meredith, Ruby F. ; Alvarez, Ronald D. ; Partridge, Edward E. ; Khazaeli, M. B. ; Lin, Chin Yu ; Macey, Daniel J. ; Austin, J. Maxwell ; Kilgore, Larry ; Grizzle, William E. ; Schlom, Jeffrey ; Lobuglio, Albert F. / Intraperitoneal radioimmunochemotherapy of ovarian cancer : A phase I study. In: Cancer Biotherapy and Radiopharmaceuticals. 2001 ; Vol. 16, No. 4. pp. 305-315.
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