- Email: [email protected]
A pilot study of sandostatin LAR in combination with human recombinant alpha interferon in treating patients with metastatic neuroendocrine tumors
3110
starting at 10 mg qmo from week two. The dosage of Sandostatin LAR was increased up to a maximum of 30 mg if there was no tumor response as assessed at three-month intervals by abdominal imaging studies. There was a two-week overlap of 290 mcg of short acting Sandostatin during the first two weeks of the study to effectively maintain the maximum therapeutic level of Sandostain in patients. Tumor marker responses (Chromogranin-A and Neuron Specific Enolase) were also evaluated every three-month interval during the study. Results: There was an overall reduction in tumor markers in 5/7 (71%) of the patients studied. Complete tumor regression (metastatic and primary tumors) were observed in 2/7 (28%) which was observed at the three month visit and was sustained for up to one year. In an additional 4/7 patients (57%) stable tumor growth was observed as defined by no appreciable growth in the cross-sectional area of the metastatic and primary tumors. In 1/7 (14%) patients no effect on tumor growth was detected despite therapy for up to 9 months. No serious adverse events were reported by any of the patients. Conclusions: This study is the first to demonstrate the clinical utility of Sandostatin LAR® when used in combination with the alpha interferon, Infergen® for controlling the growth of metastatic neuroendorine tumors. Combination treatment of Sandostatin with Interferon should be considered as a valuable regimen to treat patients with metastatic neuroendocrine tumors.
Effect Of Intestinal Alkalinization On Irinolecan (CPT-11)-Induced Diarrhea In The Golden Syrian Hamster Model Tadashi Ikegami, Partita Latham, George Washington Univ, Washington, DC; Kunihiko Kobayashi, Saitama Cancer Ctr, Saitama Japan; Kaxahikko Arimori, Miyazaki Medical Sch, Miyazaki Japan; Bernard Bouscarel, George Washington Univ, Washington, DC Background:The therapeutic efficacy of Irinotecan (CPT-11), a DNA topoisomerase inhibitor, is often limited by induction of severe late-onset diarrhea. This pro-drug and its active metabolite, SN-38, have an ~hydroxy-lactone ring that undergoes reversible hydrolysis to its carboxylate form in a pH-dependent manner. We have previously reported that the initial uptake rate of CPT-11 and SN-38 lactone by intestinal cells was significantly greeter than the carboxylate counterpart. Furthermore,the uptake rate of SN-38 correlated with induced cellular toxicity. Hypothesis:Intestinalalkalinization by sodium bicarbonate supplementation can reduce CPT-11-induceddiarrhea and intestinal damage. Methods:Onegroup of hamsters was administered 5 mg/ml of sodium bicarbonate in a 3 % sucrose solution while the control group received only sucrose solution for 2 days prior to IP injection of 100/~1 of CPT-11 (20 mg/ kg) daily for a 7 day period. After sacrificing the animals, serum, bile, and intestinal pH were determined. Percentageof water in the intestinal contents was calculated from their respective wet and dry weight. Intestinal injury was determined histopathologically. Results:Sodium bicarbonate supplementation for 7 days resulted in a dose-dependent increased intestinal pH with a maximum increase observed with 5 mg/ml. Those doses of bicarbonate did not significantly affect the serum pH. All animals receiving CPT-11 alone had diarrhea by day 5. The animals receiving CPT-11 lost weight in a CPT-11 dose-dependentmanner with a respective loss of 20 % and 31% with CPT-11 20 mg/kg and 50 mg/kg. However, bicarbonate administration reduced the body weight loss for the hamsters receiving CPT-11 (20 mg/kg) by approximately 50 %. Intestinal water content was significantly increased up to 90 % by CPT-11 injection, and was attenuated by more than 30 % by bicarbonate supplementation. This alkalinization resulted in significant improvement of the tiistopathological damage to both small and large intestinal mucose of the animals receiving CPT-11 (20 mg/kgx 7 days). Conclusions:Resultsfrom the present in vivoetudies support intestinal alkalinization by sodium bicarbonate supplementation to be a preventive mechanism against CPT-11-induceddiarrhea, probably by preventing the accumulation of SN-38 in intestinal tissue. This provides a strong rationale for the usage of bicarbonate as an adjunct to CPT-11 treatment.
3113 Treatment of Disseminated NenroeodocrioeTumours with Targeted Radintherpay Using Yttrium-90 LanraoUde Martyn E. Caplin, John R. Buscombe, David Cbao, Pierre Bouluux, Daniel Hochhauser, Royal Free Hosp, London United Kingdom; Tina A. Yong, Queen Elizabeth Hosp, Hong Kong; Irene Viroolini, Univ of Lienz, Lienz Austria; Andrew J. Hilson, Royal Free Hosp, London United Kingdom Patients with disseminated neuroendocrine tumours (NETs) may be resistant to conventional therapies. The most sensitive imaging in NETs is somatostatin receptor scintigraphy using Indium-Ill (In-111) octreoscan. Attaching a radionucleotide to imaging agents would allow targeted therapy directed against the tumour s somatostatin receptors. Aim: To assesstoxicity and preliminary evidence of efficacy of Yttrium-9O lanreotide targeted therapy. Methods: Patients were selectedfor a phase 1 toxicity trial, if they had high uptake of In-ll 1 octreoscan in sites of known tumour and had no other treatment options. A total of 10 patients were treated, 9 carcinoid patients one patient with fibrolamellar carcinoma. All patients had extensive disease with evidence of tumour growth in the 6 months preceding treatment. In all patients a standard regimen of 4-6 weekly 1 GBq Yttrium-90 (Y-90) lanreotide was used. If there was evidence of response and further clinical indication, such as previous symptom relief, a second course was started. Results: A total ol 32 cycles of treatment have been given. The only significant side effect is that most patients felt tired and lethargic from 2 to 7 days post therapy. There was bone marrow toxicity (WHO grade 2) in 2 patients with marked bone metastases. No other toxicity has been found, including no evidence of renal toxicity. There has been tumour progression and death in 3 of the patients treated. Within this group however, one patient received symptomatic relief of bone pain. One of the deaths was from an unrelated (and at the time of treatment unsuspected) adenocarcinoma, in the remainder there was evidence of disease stability. Although C.T. showed some central tumour necrosis after treatment, the reduction in tumour size was not greater than 25%. Conclusion: Y-90 labelled lanreotide appearsto be a safe therapy when given as 1 GBq per 4-6 weeks. Further controlled etud(es need to be performed to assess eff(cacy in neuroendocrine tumours.
3111 Prospective Study of Efficacy of Intederoo-2~x(INF-2a) in Metastatic Gastriooma. Alaa Abou-Saif, Homayoun Shojamanesh, Showkat 8ashir, Jeremiah Ojeaburu, Fathia Gibril, Robert T. Jensen, National Inst of Health, Bethesda, MD 8GD: INF-2~may have anti-tumor effects in patients with metastatic neuroendocrine tumors [carcinoids, pancreatic endocrine tumors (PETs)]. Whereas INF-2o~hasbeen well studied in patients with carcinoids, its efficacy in malignant PETs such as metastatic gastrinomas is less clear. This occurred because few patients have been treated and often patients with different PETsare combined. AIM: To determine the efficacy of INF-2o~inpatients with malignant gastrinomas. METHODS: 17 patients with progressive metastatic gastrinomas were included andfollowed prospectively. Conventionalimaging studies (CT, ultrasound, MRI), an octreoscan since 1994, biochemical and hematological as well as opi'~hatmotogic examinations were performed prior to and at 3 monthly cycles while on INF-2oL. Patients were treated with INF-2~(5 million units/day s.c.) and treatment was continued until progression, complete regression, or intolerable side-effects developed. Progression was >25% increase in tumor size or new lesions. A positive response was no additional tumor growth (stabilization) or a decrease in tumor size. RESULTS: The 17 patients had a mean __ 1SEM age of 49 -+ 2 yrs, fasting gastrin of 8696 +_ 3574 and all had liver metastases. The primary tumor sites were pancreas (n=9), duodenum (n=l) and unknown (n=7). 5 patients received prior chemotherapy, which had failed. The mean duration of INF-2o~treetmentwas 14_+5 mos, with 76% of patients receiving INF-2oeforat least 6 mos, 52% for 12 mos, 20% for 24 mos, and 12% for 36 mos. 10 patients (59%) had a positive response and the mean response lasted 13.5 _+ 3 mos (range 3-36 mos). In all cases the response was tumor stabilization. A positive response did not correlate with any clinical, lab, or tumor parameter. 8 patients had sideeffects including fatigue (n=3), depression (n=3), leukopenia (n=l) and retinal artery occlusion (n = 1). 4 patients discontinued treatment becausethe side-effect was severe.These results demonstrate that interferon-2o~treatmentwill causetumor stabilization in approximately two-thirds of patients with progressive gastrinomas. Even though a decrease in tumor size appearsto be an uncommon result, occurring in none of our patients, the ability of interferon2oLto stabilize tumor growth in more than one-half of patients raises the likelihood it will increase survival in some patients with progressive disease "and therefore, should be more widely used.
3114 Efficacious Long-Term Maintenance Therapy with Pantoprazole (PAN) in Patients with Zollinger-Ellison Syndrome Philippus C. Bomman, Univ of Cape Town, Cape Town South Africa; Klaus Radebold, YALE Univ, New Haven, CT; Herman J. De Baere, City Hosp, Mechelen Belgium; Louis Venter, Byk Gulden Pharmaceuticals, Cape Town South Africa; Hartmut Heinze, Renete Fischer, Byk Gulden Pharmaceuticals, Konstanz Germany AIM: To evaluate the efficacy and safety of a 3 year treatment with PAN (40 to 160mg per day) on basal acid output (BAO) and gastric mucosa in patients with Zollinger-Ellison syndrome (ZES). METHODS:The open labelled trial was divided into a screening visit, a wash-out phase (at least 5 days), a titration phase (5, 9 or 13 days) and a maintenance treatment phase (3 years). Dose titration was aimed to reduce the BAO to less than 10 mmol/h (>5 mmol/h in patients with acid reducing operations). During maintenance, 8AO was determined 12-weekly, upper endoscopies were performed every 24 weeks. RESULTS: 11 patients (8 male, 3 female; median age 56 years, range 27-74) were included into the trial from 2 study centers (10 patients in South Africa and one in Belgium). Follow up period was 4-35 (mean 24.8) months. In six patients the ZES was successfully controlled during the whole long term period (3335 months). Five patients prematurely discontinued the treatment. One patient was excluded after 4 months due to lack of compliance. Two patients were completely healed after excision of gastrinoma and two patients died within the course of the study. PAN effectively reduced BAO (normal: 0-5 mmol/h) from a mean pre-treatment value of 29.7 mmol/h to 11.9 mmol/ h after 3 months and mean values below 10 mmol/h at every other follow up visit. In the 5 patients presenting with high BAO (36 - 98 mmoVh) at entrance examination, a maintenance dose of 120 mg was mainly used and 4 patients received 160 mg for the maximally permitted period of 3 months. None of the compliant patients developed any life-threatening complications of ZES. During treatment, ECL-cell hyperplasia was found in five patients (linear in 3 patients, nodular in 2 patients). ECL-cell dysplasia was diagnosed in one patient. There was no evidence of progression to carcinoids. A total of 73 adverse events (most frequently: headache, diarrhea, dizziness and flu syndrome) were reported. Two events (duodenitis and rash) were classified as likely related to PAN. No influence of PAN on laboratory parameters was observed. CONCLUSIONS:During long-term administration with daily doses up to 120 mg, PAN was found to be a strong inhibitor of acid secretion in patients with ZES, no concerns about the safety were raised. However, a long term follow up (incl. BAO measurement and endoscopy) is required to improve the clinical outcome of the patients i.e. to detect the need of dose adjustments and histologic changes.
3112 A Pilot Study of Sandostatin LAR in Combination with Human RecombinantAlpha interferon in Treating Patients with Metastatic NeuroendocrineTumors. David S. Oh, Joseph R. Pisegna, Div of GI VA GLAHS and Dept of Medicine UCLA, Los Angeles, CA Purpose: There are no effective methods to manage patients with metastatic neuroendocrine tumors. Chemotherapywith 5FU,adrtiamycin and strepmzotocin havea 40% response ratethat is short-lived. Similarly studies of somatostatin analogs or interferons have had disappointing results. Accordingly, this study was conducted to determine the response rate of a long-acting analogue of somatostatin, Sandostatin LAR~ combined with an alpha interferon, Infergen®. Methods: The study was approved by the UCLA IRB. The study was conducted as an openlabel, prospective study. Patients with actively growing metastatic tumors and who consented to the protocol were considered for enrollment. Tumor growth was assessed using a combination of helical CT, MRI and/or Octreoscan®. Accordingly, seven patients with metastatic neuroendocrinetumors (five with hepatic metastases,one with brain metastasis and one with lung metastasis) were treated with 9 mcg of Infergen tiw in addition to Sandostatin LAR
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starting at 10 mg qmo from week two. The dosage of Sandostatin LAR was increased up to a maximum of 30 mg if there was no tumor response as assessed at three-month intervals by abdominal imaging studies. There was a two-week overlap of 290 mcg of short acting Sandostatin during the first two weeks of the study to effectively maintain the maximum therapeutic level of Sandostain in patients. Tumor marker responses (Chromogranin-A and Neuron Specific Enolase) were also evaluated every three-month interval during the study. Results: There was an overall reduction in tumor markers in 5/7 (71%) of the patients studied. Complete tumor regression (metastatic and primary tumors) were observed in 2/7 (28%) which was observed at the three month visit and was sustained for up to one year. In an additional 4/7 patients (57%) stable tumor growth was observed as defined by no appreciable growth in the cross-sectional area of the metastatic and primary tumors. In 1/7 (14%) patients no effect on tumor growth was detected despite therapy for up to 9 months. No serious adverse events were reported by any of the patients. Conclusions: This study is the first to demonstrate the clinical utility of Sandostatin LAR® when used in combination with the alpha interferon, Infergen® for controlling the growth of metastatic neuroendorine tumors. Combination treatment of Sandostatin with Interferon should be considered as a valuable regimen to treat patients with metastatic neuroendocrine tumors.
Effect Of Intestinal Alkalinization On Irinolecan (CPT-11)-Induced Diarrhea In The Golden Syrian Hamster Model Tadashi Ikegami, Partita Latham, George Washington Univ, Washington, DC; Kunihiko Kobayashi, Saitama Cancer Ctr, Saitama Japan; Kaxahikko Arimori, Miyazaki Medical Sch, Miyazaki Japan; Bernard Bouscarel, George Washington Univ, Washington, DC Background:The therapeutic efficacy of Irinotecan (CPT-11), a DNA topoisomerase inhibitor, is often limited by induction of severe late-onset diarrhea. This pro-drug and its active metabolite, SN-38, have an ~hydroxy-lactone ring that undergoes reversible hydrolysis to its carboxylate form in a pH-dependent manner. We have previously reported that the initial uptake rate of CPT-11 and SN-38 lactone by intestinal cells was significantly greeter than the carboxylate counterpart. Furthermore,the uptake rate of SN-38 correlated with induced cellular toxicity. Hypothesis:Intestinalalkalinization by sodium bicarbonate supplementation can reduce CPT-11-induceddiarrhea and intestinal damage. Methods:Onegroup of hamsters was administered 5 mg/ml of sodium bicarbonate in a 3 % sucrose solution while the control group received only sucrose solution for 2 days prior to IP injection of 100/~1 of CPT-11 (20 mg/ kg) daily for a 7 day period. After sacrificing the animals, serum, bile, and intestinal pH were determined. Percentageof water in the intestinal contents was calculated from their respective wet and dry weight. Intestinal injury was determined histopathologically. Results:Sodium bicarbonate supplementation for 7 days resulted in a dose-dependent increased intestinal pH with a maximum increase observed with 5 mg/ml. Those doses of bicarbonate did not significantly affect the serum pH. All animals receiving CPT-11 alone had diarrhea by day 5. The animals receiving CPT-11 lost weight in a CPT-11 dose-dependentmanner with a respective loss of 20 % and 31% with CPT-11 20 mg/kg and 50 mg/kg. However, bicarbonate administration reduced the body weight loss for the hamsters receiving CPT-11 (20 mg/kg) by approximately 50 %. Intestinal water content was significantly increased up to 90 % by CPT-11 injection, and was attenuated by more than 30 % by bicarbonate supplementation. This alkalinization resulted in significant improvement of the tiistopathological damage to both small and large intestinal mucose of the animals receiving CPT-11 (20 mg/kgx 7 days). Conclusions:Resultsfrom the present in vivoetudies support intestinal alkalinization by sodium bicarbonate supplementation to be a preventive mechanism against CPT-11-induceddiarrhea, probably by preventing the accumulation of SN-38 in intestinal tissue. This provides a strong rationale for the usage of bicarbonate as an adjunct to CPT-11 treatment.
3113 Treatment of Disseminated NenroeodocrioeTumours with Targeted Radintherpay Using Yttrium-90 LanraoUde Martyn E. Caplin, John R. Buscombe, David Cbao, Pierre Bouluux, Daniel Hochhauser, Royal Free Hosp, London United Kingdom; Tina A. Yong, Queen Elizabeth Hosp, Hong Kong; Irene Viroolini, Univ of Lienz, Lienz Austria; Andrew J. Hilson, Royal Free Hosp, London United Kingdom Patients with disseminated neuroendocrine tumours (NETs) may be resistant to conventional therapies. The most sensitive imaging in NETs is somatostatin receptor scintigraphy using Indium-Ill (In-111) octreoscan. Attaching a radionucleotide to imaging agents would allow targeted therapy directed against the tumour s somatostatin receptors. Aim: To assesstoxicity and preliminary evidence of efficacy of Yttrium-9O lanreotide targeted therapy. Methods: Patients were selectedfor a phase 1 toxicity trial, if they had high uptake of In-ll 1 octreoscan in sites of known tumour and had no other treatment options. A total of 10 patients were treated, 9 carcinoid patients one patient with fibrolamellar carcinoma. All patients had extensive disease with evidence of tumour growth in the 6 months preceding treatment. In all patients a standard regimen of 4-6 weekly 1 GBq Yttrium-90 (Y-90) lanreotide was used. If there was evidence of response and further clinical indication, such as previous symptom relief, a second course was started. Results: A total ol 32 cycles of treatment have been given. The only significant side effect is that most patients felt tired and lethargic from 2 to 7 days post therapy. There was bone marrow toxicity (WHO grade 2) in 2 patients with marked bone metastases. No other toxicity has been found, including no evidence of renal toxicity. There has been tumour progression and death in 3 of the patients treated. Within this group however, one patient received symptomatic relief of bone pain. One of the deaths was from an unrelated (and at the time of treatment unsuspected) adenocarcinoma, in the remainder there was evidence of disease stability. Although C.T. showed some central tumour necrosis after treatment, the reduction in tumour size was not greater than 25%. Conclusion: Y-90 labelled lanreotide appearsto be a safe therapy when given as 1 GBq per 4-6 weeks. Further controlled etud(es need to be performed to assess eff(cacy in neuroendocrine tumours.
3111 Prospective Study of Efficacy of Intederoo-2~x(INF-2a) in Metastatic Gastriooma. Alaa Abou-Saif, Homayoun Shojamanesh, Showkat 8ashir, Jeremiah Ojeaburu, Fathia Gibril, Robert T. Jensen, National Inst of Health, Bethesda, MD 8GD: INF-2~may have anti-tumor effects in patients with metastatic neuroendocrine tumors [carcinoids, pancreatic endocrine tumors (PETs)]. Whereas INF-2o~hasbeen well studied in patients with carcinoids, its efficacy in malignant PETs such as metastatic gastrinomas is less clear. This occurred because few patients have been treated and often patients with different PETsare combined. AIM: To determine the efficacy of INF-2o~inpatients with malignant gastrinomas. METHODS: 17 patients with progressive metastatic gastrinomas were included andfollowed prospectively. Conventionalimaging studies (CT, ultrasound, MRI), an octreoscan since 1994, biochemical and hematological as well as opi'~hatmotogic examinations were performed prior to and at 3 monthly cycles while on INF-2oL. Patients were treated with INF-2~(5 million units/day s.c.) and treatment was continued until progression, complete regression, or intolerable side-effects developed. Progression was >25% increase in tumor size or new lesions. A positive response was no additional tumor growth (stabilization) or a decrease in tumor size. RESULTS: The 17 patients had a mean __ 1SEM age of 49 -+ 2 yrs, fasting gastrin of 8696 +_ 3574 and all had liver metastases. The primary tumor sites were pancreas (n=9), duodenum (n=l) and unknown (n=7). 5 patients received prior chemotherapy, which had failed. The mean duration of INF-2o~treetmentwas 14_+5 mos, with 76% of patients receiving INF-2oeforat least 6 mos, 52% for 12 mos, 20% for 24 mos, and 12% for 36 mos. 10 patients (59%) had a positive response and the mean response lasted 13.5 _+ 3 mos (range 3-36 mos). In all cases the response was tumor stabilization. A positive response did not correlate with any clinical, lab, or tumor parameter. 8 patients had sideeffects including fatigue (n=3), depression (n=3), leukopenia (n=l) and retinal artery occlusion (n = 1). 4 patients discontinued treatment becausethe side-effect was severe.These results demonstrate that interferon-2o~treatmentwill causetumor stabilization in approximately two-thirds of patients with progressive gastrinomas. Even though a decrease in tumor size appearsto be an uncommon result, occurring in none of our patients, the ability of interferon2oLto stabilize tumor growth in more than one-half of patients raises the likelihood it will increase survival in some patients with progressive disease "and therefore, should be more widely used.
3114 Efficacious Long-Term Maintenance Therapy with Pantoprazole (PAN) in Patients with Zollinger-Ellison Syndrome Philippus C. Bomman, Univ of Cape Town, Cape Town South Africa; Klaus Radebold, YALE Univ, New Haven, CT; Herman J. De Baere, City Hosp, Mechelen Belgium; Louis Venter, Byk Gulden Pharmaceuticals, Cape Town South Africa; Hartmut Heinze, Renete Fischer, Byk Gulden Pharmaceuticals, Konstanz Germany AIM: To evaluate the efficacy and safety of a 3 year treatment with PAN (40 to 160mg per day) on basal acid output (BAO) and gastric mucosa in patients with Zollinger-Ellison syndrome (ZES). METHODS:The open labelled trial was divided into a screening visit, a wash-out phase (at least 5 days), a titration phase (5, 9 or 13 days) and a maintenance treatment phase (3 years). Dose titration was aimed to reduce the BAO to less than 10 mmol/h (>5 mmol/h in patients with acid reducing operations). During maintenance, 8AO was determined 12-weekly, upper endoscopies were performed every 24 weeks. RESULTS: 11 patients (8 male, 3 female; median age 56 years, range 27-74) were included into the trial from 2 study centers (10 patients in South Africa and one in Belgium). Follow up period was 4-35 (mean 24.8) months. In six patients the ZES was successfully controlled during the whole long term period (3335 months). Five patients prematurely discontinued the treatment. One patient was excluded after 4 months due to lack of compliance. Two patients were completely healed after excision of gastrinoma and two patients died within the course of the study. PAN effectively reduced BAO (normal: 0-5 mmol/h) from a mean pre-treatment value of 29.7 mmol/h to 11.9 mmol/ h after 3 months and mean values below 10 mmol/h at every other follow up visit. In the 5 patients presenting with high BAO (36 - 98 mmoVh) at entrance examination, a maintenance dose of 120 mg was mainly used and 4 patients received 160 mg for the maximally permitted period of 3 months. None of the compliant patients developed any life-threatening complications of ZES. During treatment, ECL-cell hyperplasia was found in five patients (linear in 3 patients, nodular in 2 patients). ECL-cell dysplasia was diagnosed in one patient. There was no evidence of progression to carcinoids. A total of 73 adverse events (most frequently: headache, diarrhea, dizziness and flu syndrome) were reported. Two events (duodenitis and rash) were classified as likely related to PAN. No influence of PAN on laboratory parameters was observed. CONCLUSIONS:During long-term administration with daily doses up to 120 mg, PAN was found to be a strong inhibitor of acid secretion in patients with ZES, no concerns about the safety were raised. However, a long term follow up (incl. BAO measurement and endoscopy) is required to improve the clinical outcome of the patients i.e. to detect the need of dose adjustments and histologic changes.
3112 A Pilot Study of Sandostatin LAR in Combination with Human RecombinantAlpha interferon in Treating Patients with Metastatic NeuroendocrineTumors. David S. Oh, Joseph R. Pisegna, Div of GI VA GLAHS and Dept of Medicine UCLA, Los Angeles, CA Purpose: There are no effective methods to manage patients with metastatic neuroendocrine tumors. Chemotherapywith 5FU,adrtiamycin and strepmzotocin havea 40% response ratethat is short-lived. Similarly studies of somatostatin analogs or interferons have had disappointing results. Accordingly, this study was conducted to determine the response rate of a long-acting analogue of somatostatin, Sandostatin LAR~ combined with an alpha interferon, Infergen®. Methods: The study was approved by the UCLA IRB. The study was conducted as an openlabel, prospective study. Patients with actively growing metastatic tumors and who consented to the protocol were considered for enrollment. Tumor growth was assessed using a combination of helical CT, MRI and/or Octreoscan®. Accordingly, seven patients with metastatic neuroendocrinetumors (five with hepatic metastases,one with brain metastasis and one with lung metastasis) were treated with 9 mcg of Infergen tiw in addition to Sandostatin LAR
A-613