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PubMed2003

Intraperitoneal radioimmunotherapy in treating peritoneal carcinomatosis of colon cancer in mice compared with systemic radioimmunotherapy.

Peritoneal spread is one of major causes of mortality in colorectal cancer patients. In the current investigation, the efficacy of radioimmunotherapy (RIT) with i.p. administration of an anti-colorectal cancer IgG1, 131I-A7, was compared to that with i.v. administration in BALB/c female mice bearing peritoneal nodules of LS180 human colon cancer cells, at the same toxicity level. Distribution of either i.p. or i.v. administered 131I-A7 and i.p. administered irrelevant 131I-HPMS-1 was assessed. Based on the results of toxicity determination at increments of 2 MBq and estimated dosimetry, an i.p. dose of 11 MBq and an i.v. dose of 9 MBq were chosen for treatment. Mice were monitored for long-term survival: untreated mice (n = 11), mice undergoing i.p. RIT with 131I-A7 (n = 11), mice undergoing i.v. RIT with 131I-A7 (n = 11) and mice undergoing non-specific i.p. RIT with 131I-HPMS-1 (n = 5). Intraperitoneal injection of 131I-A7 produced faster and greater tumor accumulation than i.v. injection: 34.2 +/- 16.5% of the injected dose per g (% ID/g) and 11.1 +/- 3.6% ID/g at 2 h, respectively (P < 0.0001). Consequently, cumulative radioactivity in tumors was 1.73-fold higher with i.p. injection. 131I-HPMS-1 did not show specific accumulation. Non-specific RIT with 131I-HPMS-1 (mean survival, 26.0 +/- 2.5 days) did not affect the survival as compared to no treatment (26.7 +/- 1.9 days). Intravenous RIT with 131I-A7 prolonged the survival of mice to 32.8 +/- 1.8 days (P < 0.01). Intraperitoneal RIT with 131I-A7 improved the survival more significantly and attained cure in 2 of 11 mice (P < 0.05 vs. i.v. RIT). In conclusion, i.p. RIT is more beneficial in treating peritoneal carcinomatosis of colon cancer than i.v. RIT in a murine model.

Animals↗

PubMed2001

Response to radioimmunotherapy correlates with tumor pO2 measured by EPR oximetry in human tumor xenografts.

The efficacy of radiation treatment depends upon local oxygen concentration. We postulated that the variability in responsiveness of tumor xenografts to a fixed dose of radioimmunotherapy might be related to the tumor pO2 at the time that radioimmunotherapy was administered. We evaluated the growth of xenografts of CALU-3 tumors, a non-small cell lung carcinoma, in response to an 8.9-MBq dose of 131I-RS-7-anti-EGP-1 and correlated tumor growth rate with initial tumor pO2 measured by EPR oximetry. The greatest growth delay in response to radioimmunotherapy had the highest initial pO2, and the fastest-growing tumors had the lowest initial pO2. We then determined the dynamic effect of radioimmunotherapy on tumor pO2 by serial measurements of pO2 for 35 days after radioimmunotherapy. This information could be important for ascertaining the likelihood that a tumor will respond to additional doses as part of a multiple dose scheme. Serial tumor pO2 measurements may help identify a window of opportunity when the surviving tumor regions will be responsive to a second round of radioimmunotherapy or a second therapeutic modality such as chemotherapy or an anti-vascular agent. After radioimmunotherapy, there was an increase in tumor pO2 followed by a decrease below initial levels in most mice. Thus defined times may exist when a tumor is more or less radiosensitive after radioimmunotherapy.

Animals↗

PubMed1993

Comparison of radioimmunotherapy and external beam radiotherapy in colon cancer xenografts.

Radioimmunotherapy and external beam radiotherapy were compared in a nude mouse human colon cancer model. Radioimmunotherapy was delivered by intraperitoneal injection of 90Y-labeled anticarcinoembryonic antigen monoclonal antibody (anti-CEA MAB). Single fraction external beam radiotherapy was delivered using a 60Co teletherapy unit. Control groups received saline, unlabeled anti-CEA monoclonal antibody and labeled nonspecific monoclonal antibody. Subcutaneous CEA-expressing LS174T human colon carcinoma tumors were measured over time. Tumor growth suppression was expressed as delay to reach 2g compared to saline controls. Unlabeled anti-CEA monoclonal antibody and labeled nonspecific monoclonal antibody had no effect. External beam radiotherapy of 300, 600, 1000 and 2000 cGy produced growth delays of 3, 12, 17, and 22 days, respectively. Radioimmunotherapy with 120 microCi, 175 microCi, and 225 microCi resulted in growth delays of 20, 34, and 36 days. Estimated absorbed tumor dose was 1750 cGy in the 120 microCi group. Similar comparisons were done with the more radioresistant WiDr human colon carcinoma cell line. External beam radiotherapy doses of 400, 800, 1200, and 1600 cGy resulted in growth delays of 6, 21, 36 and 48 days, respectively. Radioimmunotherapy of 120 microCi and 175 microCi resulted in growth delays of 9 and 19 days, respectively. The 120 microCi dose delivered an estimated absorbed tumor dose of 1080 cGy to WiDr tumors. In summary, for the radiosensitive LS174T line, radioimmunotherapy produced biologic effects that were comparable to a similar dose of single fraction external beam radiotherapy. For the more radioresistant WiDr tumor, radioimmunotherapy produced a biologic effect which was less than a similar dose of single fraction external beam radiotherapy. These studies suggest that a tumor's response to radioimmunotherapy relative to that of external beam radiotherapy is, in part, dependent on tumor radiosensitivity and repair capacity.

Animals↗

PubMed1989

[Radioimmunotherapy combined with chemotherapy and immunotherapy for nude mice bearing human hepatocellular carcinoma].

A comparative study of multiple modalities, radioimmunotherapy combined with cisplatin and MBV was made. The tumor size and macrophage activity (acid phosphatase) were measured after treatment. The results showed that the tumor inhibition rates were 48, 55, 74, 76, 79% in radioimmunotherapy, cisplatin, radioimmunotherapy + MBV, radioimmunotherapy + cisplatin and radioimmunotherapy + MBV + cisplatin groups, respectively. Radioimmunotherapy was effective in controlling tumor growth, especially in sequential treatment by two injections. Both cisplatin and MBV could increase therapeutic effect of radioimmunotherapy. Therefore, combination of the three modalities is the best choice for tumor growth control. The effectiveness of MBV may be related to the increase of macrophage activity. Preliminary clinical results were satisfactory. Decline in serum AFP level and shrinkage of tumor were observed in 80% (12/15) and 65% (13/20) of the patients. It is suggested that combination of multiple treatment modalities may provide an important approach to treat moderately advanced liver cancer.

Animals↗

PubMed1996

Radioimmunotherapy: recent results and future directions.

PURPOSE: To review antibody structure, function, and production; suitable radioisotopes for radioimmunotherapy; challenges facing the field; recent clinical results; toxicity; and future directions. DESIGN: The radioimmunotherapy literature was reviewed, with an emphasis on clinical results and future directions. RESULTS: The highest complete response rates (overall, approximately 50%) have been achieved in patients with B-cell non-Hodgkin's lymphoma. Challenges that currently face radioimmunotherapy include circulating free antigen, binding of antibodies to nonspecific Fc receptors, insufficient tumor penetration, antigenic heterogeneity and insufficient antigen expression, antigenic modulation, and development of human antimouse antibodies. Possible approaches to these challenges, including high-dose radioimmunotherapy and chemotherapy followed by autologous bone marrow transplantation, the use of radionuclides such as yttrium 90 (90Y) and copper 67 (67Cu), and the development of humanized and bifunctional antibodies, are under investigation. CONCLUSION: Although radioimmunotherapy is a relatively new field, substantial progress has been made. Additional research will ultimately resolve many of the challenges that currently face radioimmunotherapy and hopefully lead to the cure of some currently incurable malignancies.

Animals↗

PubMed1994

Experimental radioimmunotherapy. A brief overview.

This overview highlights the use of experimental models in selecting monoclonal antibodies and radiolabels with promise for clinical radioimmunotherapy, discusses some of the experimental therapeutic approaches being studies in these models, and reviews some of the limitations of animal models caused by the allometric and other differences between man and mouse. These differences in scale must be considered when attempting to extrapolate animal radioimmunotherapy study data to human trials of radioimmunotherapy. With appropriate recognition of their limitations, experimental models of radioimmunotherapy have proven valuable and will continue to play a critical role as the place to first study innovations in radioimmunotherapy, before extension of the most promising reagents and treatment concepts into clinical therapeutic trials.

Animals↗

PubMed1997

Radioimmunotherapy of solid tumors: a review "of mice and men".

Radioimmunotherapy in lymphoma is crossing the threshold to become a standard mode of treatment. Whereas in solid tumors in preclinical studies, radioimmunotherapy has proven to be superior to conventional chemotherapy, clinical success is still limited. The purpose of this brief review is to analyze recent developments in preclinical as well as clinical radioimmunotherapy of solid, CEA-expressing tumors. Advances in experimental radioimmunotherapy are characterized by the development of metastatic, rather than subcutaneous, tumor models in nude mice, which seem to reflect the actual clinical situation much more accurately. Furthermore, the recent development of strategies to reduce the renal accretion of antibody fragments and peptides enables the use of such smaller molecules for therapy, especially those also labeled with radiometals and other forms of intracellularly retained radionuclides. Recent developments in clinical radioimmunotherapy are characterized by a trend toward the treatment of small-volume and micrometastatic disease, as is the case, e.g., in adjuvant settings. Interestingly, despite dramatic differences in size, weight and percent-of-injected-dose-per-gram uptake values, only small differences between animal models and the actual patient situation exist with respect to activity concentrations (in microCi/gram) in the tumors and tissues. Because the activity concentration over time determines the radiation absorbed dose, and thus biological effects, we postulate that animal models should be able to predict actual clinical scenarios fairly well. These findings could be used as guidelines in the design of future preclinical, as well as clinical, trials.

Animals↗

PubMed2000

Pre-targeted radioimmunotherapy of human colon cancer xenografts in athymic mice using streptavidin-CC49 monoclonal antibody and 90Y-DOTA-biotin.

Radioimmunotherapy of solid malignancies using directly labelled 90Y-monoclonal antibodies has been associated in clinical trials with dose-limiting bone marrow toxicity. Our objective in this study was to evaluate the efficacy and toxicity of an alternative two-step pre-targeted radioimmunotherapy protocol for the treatment of human colon cancer. The two-step protocol consisted of administration of the tumour-associated glycoprotein (TAG-72) monoclonal antibody CC49 conjugated to streptavidin, followed by administration of 90Y-DOTA-biotin. Swiss nu/nu athymic mice bearing subcutaneous LS174T human colon cancer xenografts were injected intraperitoneally with streptavidin-CC49 (250 micrograms), followed 40 h later by an intravenous injection of 90Y-DOTA-biotin (900 microCi, 40 micrograms). Tumour growth was measured over 25 days and compared with that in control mice receiving no treatment. Bone marrow and normal tissue toxicity was determined by peripheral blood leucocyte counts and by monitoring the body weight of the animals. Pre-targeted radioimmunotherapy resulted in a modest (30-40%) decrease in the mean tumour growth rate in treated mice compared to control animals. There was no change in body weight following treatment and peripheral blood leucocyte counts remained within the normal range. Pre-targeted radioimmunotherapy was safe at administered amounts of 90Y radioactivity, which were at least nine-fold higher than those previously determined to be lethal using directly labelled 90Y-monoclonal antibodies. The results of this study are promising for the application of pre-targeted radioimmunotherapy using streptavidin-CC49 and 90Y-DOTA-biotin for the treatment of advanced colorectal cancer in humans.

Animals↗

PubMed2003

Pretargeted radioimmunotherapy of cancer: progress step by step.

To enhance the therapeutic efficacy of radioimmunotherapy of cancer, several pretargeting strategies have been developed. In pretargeted radioimmunotherapy, the tumor is pretargeted with an antibody construct that has affinity for the tumor-associated antigen on the one hand and for a radiolabeled hapten on the other. The radiolabeled hapten is administered in a later phase, preferably after the antibody construct has cleared from the circulation. In pretargeted radioimmunotherapy, 2 main approaches can be distinguished: pretargeting strategies based on the avid interaction between streptavidin (SA) or avidin and biotin, and pretargeting strategies based on the use of bispecific antibodies. In pretargeting strategies based on biotin and SA or avidin, the use of a clearing agent that could remove the pretargeting construct from the circulation markedly improved the targeting of the radiolabeled biotin to the tumor. Thus, multistep injection schemes in which 3-5 different agents are subsequently injected were developed. In bispecific antibody-based pretargeting strategies, the use of bivalent haptens improved the efficacy of the tumor targeting, and a 2-step pretargeted radioimmunotherapy strategy is now being tested in cancer patients. Preclinical studies as well as studies on cancer patients have shown that these pretargeting strategies can result in higher radiation doses to the tumor than can directly radiolabeled antitumor antibodies. Here, the development and state of the art of the most effective approaches for pretargeted radioimmunotherapy are reviewed.

Animals↗

PubMed1992

[Evaluation of radioimmunotherapy in the multimodality treatment of hepatocellular carcinoma (HCC)].

The evaluation of radioimmunotherapy using 131I-anti HCC isoferritin IgG antibody in the multimodality treatment of HCC was reported. Forty three patients with surgically verified unresectable HCC have been treated by radioimmunotherapy as a part of multimodality treatment during 1985-1990. The short-term responses and prolong survival were compared with that in control group of 39 patients with HCC receiving conventional multimodality treatment. The rates of tumor shrinkage, AFP level decline and second resection in radioimmunotherapy group were 67.4% (29/43), 69.6% (16/23) and 30.2% (13/43) respectively, significantly higher than those in control group 23.1% (15/39), 40.0% (8/20) and 10.3% (4/39) respectively. The 1, 3, 5-year survival rates were 61.5%, 40.4% and 35.5% in radioimmunotherapy group, however, in control group were 51.3%, 20.1% and 15.5%, respectively. The results suggested that radioimmunotherapy is one of modalities of choice, particularly for the treatment of unresectable HCC in the multimodality treatment regimen.

Adult↗

PubMed1992

5-Iododeoxyuridine increases the efficacy of the radioimmunotherapy of human tumors growing in nude mice.

Recently, there has been much interest in the use of radionuclide conjugated monoclonal antibodies for the treatment of human malignancies. One way to potentially maximize the therapeutic effectiveness of radioimmunotherapy would be to sensitize tumor cells to the radiation dose delivered by the antibody. Since radioimmunotherapy can potentially treat disseminated disease, including micrometastasis, we chose to study a halogenated pyrimidine radiosensitizer, a class of compounds that affect nonhypoxic cells. 5-Iododeoxyuridine, administered with pyrimidine metabolism modulators, increased the therapeutic effectiveness of radioimmunotherapy, resulting in individual cures of human tumors growing in BALB/c nu/nu (nude) mice. 5-Iododeoxyuridine was administered with N-(phosphonacetyl)-L-aspartic acid and 5-fluoro-deoxycytidine plus tetrahydrouridine. This drug treatment was combined with radioimmunotherapy using 131I conjugated to a monoclonal antibody, Mc5. Mc5 binds to a mucin component of the human milk fat globule. This antigen is expressed on the surface of MX-1 cells, the transplantable human tumor used in this study. Tumor-bearing mice treated with both the drug protocol and 131I-Mc5 (540 microCi, 10 microCi/micrograms) showed a regression in average tumor volume. The average tumor volume was reduced below the initial size at treatment for 50 days; two of five cures were obtained. Neither cures nor regressions were observed with either the drug or antibody treatments alone. Our results indicate the potential for increasing the therapeutic effectiveness of radioimmunotherapy of human solid tumors with halogenated pyrimidines.

Animals↗

PubMed1997

Recent progress in radioimmunotherapy for cancer.

Radioimmunotherapy allows for the delivery of systemically targeted radiation to areas of disease while relatively sparing normal tissues. Despite numerous challenges, considerable progress has been made in the application of radioimmunotherapy to a wide variety of human malignancies. The greatest successes have occurred in the treatment of hematologic malignancies. Radioimmunotherapy, with or without stem-cell transplant support, has produced substantial complete remission rates in chemotherapy-resistant B-cell lymphomas. Nonmyeloablative regimens have shown so much promise that they are now being tested as initial therapy for low-grade B-cell lymphomas. Although solid tumor malignancies have been less responsive to radioimmunotherapy, encouraging results have been obtained with locoregional routes of administrations, especially when the tumor burden is small. Greater tumor-to-normal tissue ratios are achievable with regional administration. Even with intraperitoneal and intrathecal administration, bone marrow suppression remains the dose-limiting toxicity. Ongoing research into new targeting molecules, improved chelation chemistry, and novel isotope utilization is likely to extend the applications of this strategy to other tumor types. The potential for radioimmunotherapy will be enhanced if this modality can be optimally adapted for integration with other agents and if the administration method can be tailored to the type and distribution of malignancy.

Hematologic Neoplasms↗

PubMed2001

Radioimmunotherapy in patients with head and neck squamous cell carcinoma: initial experience.

BACKGROUND: Despite improvements in locoregional treatment of stages III/IV squamous cell carcinoma of the head and neck (HNSCC), local and distant failure rates remain high. An effective adjuvant therapy is required for these patients. Among novel approaches is radioimmunotherapy, in which monoclonal antibodies (MAbs) are used for selective delivery of radiation to tumor cells. METHODS: The suitability of 186Re-labeled chimeric MAb U36 (186Re-cMAb U36) for radioimmunotherapy was evaluated in a phase I study, with radiation dose escalating steps of 11, 27, and 41 mCi/m2. Tumor targeting was monitored with a gamma camera, and the maximum tolerated dose was established in 13 patients with recurrent or metastatic disease. RESULTS: Administrations were well tolerated, and excellent targeting of tumor lesions was seen. Myelotoxicity was the only toxicity observed, resulting in dose-limiting toxicity in two patients treated with 41 mCi/m2. The MTD was established at 27 mCi/m2. A marked reduction in tumor size was observed in two patients, another showed stable disease for 6 months. CONCLUSIONS: Radioimmunotherapy with 186Re-cMAb U36 seems to be well tolerated, with bone marrow being the dose-limiting organ. The observation of antitumor effects is encouraging for further development of radioimmunotherapy for HNSCC.

Aged↗

PubMed2003

Experimental radioimmunotherapy of small peritoneal metastases of colorectal origin.

Radioimmunotherapy using radiolabeled monoclonal antibodies (MoAbs) directed against tumor-associated antigens might be an effective treatment modality for small volume disease. Our aim was to optimize an experimental model of radioimmunotherapy for small peritoneal metastases of colorectal origin using the anti-CEA MoAb MN-14. In nude mice with intraperitoneal (i.p.) LS174T tumors, a protein dose-escalation study was carried out to determine the maximal dose of radioiodinated MN-14 to be used in radioimmunotherapy. The biodistribution of radioiodinated MN-14 was determined after intravenous (i.v.) and i.p. administration. Finally, the therapeutic efficacy of escalating activity doses of (131)I-labeled MN-14 (62.5-500 microCi) was assessed and compared to that of unlabeled MN-14 or 500 microCi of (131)I-labeled irrelevant control antibody. At protein doses higher than 25 microg, uptake in tumor was reduced, presumably due to saturation of tumor antigen. During the first 24 hours i.p. administration led to higher tumor uptake and higher tumor:blood ratios than i.v. administration. Median survival of the control groups was 38 days (unlabeled MN-14) and 52 days ((131)I-labeled nonspecific antibody). Median survival of the groups treated with increasing activity doses of (131)I-labeled MN-14 was 42 days (62.5 microCi), 49 days (125 microCi), 63 days (250 microCi) and 101 days (500 microCi), respectively (p < 0.0001 compared to unlabeled MN-14). The present study shows that the anti-CEA-antibody MN-14 preferentially accumulates in i.p. LS174T tumor xenografts after both i.p. and i.v. administration. Intraperitoneal radioimmunotherapy using (131)I-labeled MN-14 delays significantly the outgrowth of peritoneal LS174T metastases, even at relatively low activity doses.

Animals↗

PubMed2003

Locoregional radioimmunotherapy in selected patients with malignant glioma: experiences, side effects and survival times.

UNLABELLED: Prognosis of malignant glioma is very unfavourable mainly due to minimal tumour remnants in the peritumoural tissue. Intralesionally applied radioimmunotherapy is a possible therapeutical option with the potential to improve survival of patients with malignant glioma. We investigated side effects and survival after surgery, conventional radiotherapy and additional radioimmunotherapy with labelled tenascin-antibodies in patients with malignant glioma. METHODS: Since 1995, 37 patients were treated with radioimmunotherapy after resection and radiotherapy of a malignant glioma. Patients received antibodies labelled with yttrium-90 and iodine-131 in different doses into the tumour cavity via a previously implanted ommaya-reservoir. Treatment was applied in up to 8 cycles (mean 2.96 cycles) in time intervals of 6-8 weeks. Mean age was 46 years, histology was anaplastic astrocytoma in 13 patients and glioblastoma in 24 patients. RESULTS: For the whole group median survival time has not yet been reached. For glioblastoma the median survival time is 17 months, 5-year survival probability for anaplastic astrocytoma is 85% approximately. Quality of life was acceptable. Acute side effects following treatment were headache, seizures and worsening of pre-existing neurological symptoms. Late side effects were skin necrosis and, in 1 case, a delayed aphasia probably due to a vascular lesion. CONCLUSION: Radioimmunotherapy prolonged survival time in a selected group of patients with malignant gliomas as compared to a historical control group. Patients with anaplastic astrocytomas seem to have more benefit from this therapy than patients with glioblastomas.

Adult↗

PubMed1999

Preclinical evaluation of chimeric L6 antibody for the treatment of Kaposi's sarcoma with radioimmunotherapy.

L6 is a murine IgG2a monoclonal antibody with panadenocarcinoma reactivity. Chimeric L6 (ChL6), the variable region of murine L6 combined with a human IgG1 constant region, has been used in clinical trials for the delivery of radioimmunotherapy to patients with breast cancer. AIDS-associated Kaposi's sarcoma (KS), a malignancy of vascular endothelium, may be an excellent candidate for systemic radioimmunotherapy because KS is well vascularized and radioresponsive. Because ChL6 has been noted to bind vascular endothelium, our hypothesis was that ChL6 will recognize and bind KS tumors making this a potentially useful antibody for the treatment of KS with radioimmunotherapy. To test this hypothesis, 4 human KS spindle cell cultures established from cutaneous punch biopsy specimens (KS-MR, KS-NO, KS-JD and KS 6-3E) and one well-characterized human KS cell line (KS Y-1) were assessed for L6 immunoreactivity. All 5 cell cultures were L6 positive by immunohistochemistry. KS Y-1 cells grown as nude mouse xenografts were also L6 positive by immunohistochemistry. Competitive binding assays performed on the KS Y-1 and KS 6-3E cell cultures showed high density and high affinity cell binding. Biodistribution experiments performed on nude mice with KS Y-1 xenografts demonstrate tumor targeting by ChL6. These findings indicate that ChL6 may be a useful antibody for the radioimmunotherapy of KS. Future experiments will assess the therapeutic efficacy of radiolabeled ChL6 with and without concurrent systemic radiosensitizing chemotherapy.

Acquired Immunodeficiency Syndrome↗

PubMed2002

Randomized controlled trial of yttrium-90-labeled ibritumomab tiuxetan radioimmunotherapy versus rituximab immunotherapy for patients with relapsed or refractory low-grade, follicular, or transformed B-cell non-Hodgkin's lymphoma.

PURPOSE: Radioimmunotherapy combines biologic and radiolytic mechanisms to target and destroy tumor cells, thus offering a needed therapeutic alternative for refractory non-Hodgkin's lymphoma (NHL) patients. This phase III randomized study compares the novel radioimmunotherapy yttrium-90 ((90)Y) ibritumomab tiuxetan with a control immunotherapy, rituximab, in 143 patients with relapsed or refractory low-grade, follicular, or transformed CD20(+) transformed NHL. PATIENTS AND METHODS: Patients received either a single intravenous (IV) dose of (90)Y ibritumomab tiuxetan 0.4 mCi/kg (n = 73) or rituximab 375 mg/m(2) IV weekly for four doses (n = 70). The radioimmunotherapy group was pretreated with two rituximab doses (250 mg/m(2)) to improve biodistribution and one dose of indium-111 ibritumomab tiuxetan for imaging and dosimetry. The primary end point, overall response rate (ORR), was assessed by an independent, blinded, lymphoma expert panel. RESULTS: ORR was 80% for the (90)Y ibritumomab tiuxetan group versus 56% for the rituximab group (P =.002). Complete response (CR) rates were 30% and 16% in the (90)Y ibritumomab tiuxetan and rituximab groups, respectively (P =.04). An additional 4% achieved an unconfirmed CR in each group. Kaplan-Meier estimated median duration of response was 14.2 months in the (90)Y ibritumomab tiuxetan group versus 12.1 months in the control group (P =.6), and time to progression was 11.2 versus 10.1 months (P =.173) in all patients. Durable responses of > or = 6 months were 64% versus 47% (P =.030). Reversible myelosuppression was the primary toxicity noted with (90)Y ibritumomab tiuxetan. CONCLUSION: Radioimmunotherapy with (90)Y ibritumomab tiuxetan is well tolerated and produces statistically and clinically significant higher ORR and CR compared with rituximab alone.

Adult↗

PubMedDate not supplied

Radioimmunotherapy after chemotherapy compared to chemotherapy alone in the treatment of advanced ovarian cancer: a matched analysis.

Ovarian cancer has an overall five-year survival of around 30% in spite of complete remissions being obtained after optimal surgery and platinum-based chemotherapy. Previous studies have indicated a survival advantage for patients treated with radiolabelled monoclonal antibodies (radioimmunotherapy). We report here on the survival of patients who received single-dose intraperitoneal radioimmunotherapy after having achieved complete remission with standard management. Twenty-five patients with epithelial ovarian cancer, stages Ic-IV, received adjuvant intraperitoneal radioimmunotherapy following completion of conventional chemotherapy. On achieving complete remission they receive once 25 mg of HMFG1 labelled with 18 mCi/m2. Controls for cases were sought from the database of the North Thames ovary group (NTOG). Controls were selected on the basis of stage, histological grade and type, and age of patient at diagnosis. Kaplan-Meier survival plots were constructed for cases and controls and subjected to statistical analysis with the log-rank test. Additionally, using a database of 84 NTOG patients known to be disease-free at the end of chemotherapy, estimated survival curves were constructed using Cox's proportional hazards regression model. Close matches were found for 20 of the 25 patients. Median survival has not been reached at a median follow-up of 59 months for cases and 27 months for controls. Survival at five years is 80% for cases and 55% for controls (p=0.0035). The Cox model estimates long-term (10-year) survival of 70% for patients who received radioimmunotherapy, compared to 32% for those that did not (p=0.003). All patients developed serological evidence of human anti-mouse antibody (HAMA). This study shows a likely survival benefit for patients with ovarian cancer who receive intraperitoneal radioimmuno-therapy in the adjuvant setting.

Adult↗