Clinical evaluation of r alpha-2a interferon in malignant carcinoid and other neuroendocrine tumors. Patients biological characterization by hormonal assays and tumor markers

Nel 1988 é stato avviato uno studio sui tumori neuroendocrini.

Lo studio (Protocollo 88/4) aveva l’obiettivo di valutare l’attività antitumorale e la tollerabilità dell’interferone ricombinante di tipo alpha in pazienti con tumori neuroendocrini non operabili e/o metastatici e di studiare, in pazienti non responsivi all’interferone, con scintigrafia 131I-MIBG positiva, l’attività antineoplastica della meta-iodobenzilguanidina.

Sono stati arruolati 82 pazienti.

Lo studio ha dimostrato l’efficacia dell’interferone ricombinante -2a nel controllo della sindrome da carcinoide, mentre è risultata limitata l’attività nell’indurre regressione tumorale. Tra i trattamenti di II linea la meta-iodobenzilguanidina appare promettente sprattutto nei pazienti con basso carico tumorale e sintomatici.

Centri partecipanti :                             Centro Rifer. Oncologico di AVIANO (PN)

Istituto Oncologico, BARI

Ospedali Riuniti di BERGAMO

Ospedale Regionale di BOLZANO

Spedali Civili di BRESCIA

Ospedale Civile di BUSTO ARSIZIO (VA)

Ospedale Civile di CESENA (FO)

Ospedale S. Anna di COMO

Ospedale Valduce di COMO

Centro Oncologico G. Porfiri, LATINA

Ospedale Vito Fazzi di LECCE

Ospedale Civile di LEGNAGO (VR)

Ospedale Civile C. Poma, MANTOVA

Istituto Nazionale Tumori – OMB, MILANO

Ospedale Fatebenefratelli di MILANO

Ospedale S. Carlo, MILANO

Ospedale S. Raffaele, MILANO

Ospedale S. Gerardo di MONZA (MI)

Ospedale Don Calabria, NEGRAR (VR)

Ospedale S. Luigi Gonzaga, ORBASSANO (TO)

Ospedale Civile di PADOVA

Ospedale Cervello di PALERMO

Policlinido di PALERMO

Policlinico S. Matteo di PAVIA

Clinica S. Rossore di PISA

Ospedale degli Infermi, RIMINI (FO)

Ospedale Regina Elena, ROMA

Ospedale Civile di SARONNO (VA)

Ospedale S. Maria, TERNI

Ospedale Civile di TRAPANI

Ospedale di Circolo di VARESE

Ospedale Civile di VERONA

Ospedale Civile di VICENZA

Riferimenti Bibliografici:

  • Salvage treatment after r-interferon alpha-2a in advanced neuroendocrine tumors.
    (Zilembo N, Buzzoni R, Bajetta E, Di Bartolomeo M, de Braud F, Castellani R, Maffioli L, Celio L, Villa E, Lorusso V, et al.).
    Acta Oncol. 1993;32(2):245-50.


The use of inteferon (IFN) in neuroendocrine advanced tumors has achieved control of hormonal symptoms but low objective tumor response rate. In patients resistant to, or failing on, IFN a second line treatment may be required. Seventeen patients having received recombinant IFN alpha-2a as last treatment entered the study. There were 12 carcinoids, 3 medullary thyroid carcinomas, one Merkel cell carcinoma, and one neuroendocrine pancreatic tumor. Two different treatments were used: one radiometabolic therapy with metaiodobenzylguanidine (MIBG) in 3 patients with high MIGB uptake and one polychemotherapy regimen, including streptozotocin 500 mg/m2 intravenously days 1, 2, 3 and epirubicin 75 mg/m2 intravenously day 1, in the remaining 14 patients. Stable disease with relief of symptoms and tumor marker reduction was obtained in two patients receiving MIGB therapy, whereas the third patient had progressive disease. In the chemotherapy group only one partial response was obtained and neither tumor marker reduction nor subjective improvement were seen. Our second-line treatment was not especially effective but may be considered for rapidly progressive and/or symptomatic disease. The radiometabolic therapy appears promising in symptomatic patients with small tumor burden whereas our chemotherapy regimen appears ineffective.

PMID: 8391833   [PubMed – indexed for MEDLINE]

Download articolo: Acta Oncol. 32 245-250, 1993


  • Treatment of carcinoid syndrome with recombinant interferon alpha-2a.
    (Di Bartolomeo M, Bajetta E, Zilembo N, de Braud F, Di Leo A, Verusio C, D’Aprile M, Scanni A, Barduagni M, Barduagni A [corrected to Barduagni M], et al.).
    Acta Oncol. 1993;32(2):235-8.


Erratum in
Acta Oncol 1993;32(5):592.


The prognosis and the quality of life of patients with carcinoid tumors is related either to symptoms from the substances secreted or to progressive tumor growth. Medical treatment with cytotoxic agents is of marginal value for increasing life expectancy and reducing clinical symptoms. Recent studies with interferon have shown interesting results. In the present investigation, 22 patients with carcinoid tumors and syndrome were treated with recombinant interferon alpha-2a (r-IFN alpha-2a) at the dose of 6 x 10(6) IU intramuscularly daily for 8 weeks and three times weekly thereafter. The primary tumor was localized in the foregut (n = 11), midgut (n = 7), hindgut (n = 1), and unknown site (n = 3). Most cases had liver metastasis. Seventeen patients had elevated 5-hydroxyindoloacetic acid (5-HIAA) excretion and 5 had flushing and/or diarrhea as the only clinical manifestation. Six cases presented a complete syndrome (flushing, diarrhea and 5-HIAA excretion). Control of symptoms was obtained in 80% and a 5-HIAA level reduction in 58% of the patients. The interferon treatment was more effective for control of the carcinoid syndrome than for control of tumor growth. The treatment was well tolerated and fever, myalgia, anorexia and fatigue were the most frequent side-effects.

PMID: 7686766   [PubMed – indexed for MEDLINE]

Download articolo: Acta Oncol. 1993


  • Treatment of metastatic carcinoids and other neuroendocrine tumors with recombinant interferon-alpha-2a. A study by the Italian Trials in Medical Oncology Group.
    (Bajetta B, Zilembo N, Di Bartolomeo M, Di Leo A, Pilotti S, Bochicchio AM, Castellani R, Buzzoni R, Celio L, Dogliotti L, et al.).
    Cancer. 1993 Nov 15;72(10):3099-105.

    Using a wide range of interferon (IFN) doses and schedules, a number of authors have found them to be active against neuroendocrine tumors.


To verify the clinical activity of IFN, 49 evaluable patients with advanced stage low- and intermediate-grade neuroendocrine tumors were treated with recombinant IFN-alpha-2a at a daily dose of 6 x 10(6) IU intramuscularly for 8 weeks, and 3 times weekly thereafter. The predominant histotype was carcinoid, although a few cases had malignant islet cell tumors, medullary thyroid carcinoma, Merkel cell carcinoma, or other neuroendocrine tumors. All of the patients had measurable lesions and most had multiple sites. Carcinoid syndrome was present in 14 cases.

After a median treatment duration of 6 months, complete regression was achieved in 1 of the 7 cases of medullary thyroid carcinoma, and partial response was observed in 4 of 34 carcinoids. Response duration ranged from 1-11 months. Control of the syndrome was obtained in nine patients and a greater than or equal to 50% reduction of 5-hydroxyindoleacetic acid in eight patients. The treatment was well-tolerated. The most frequently observed side effects were fever, flu-like syndrome, and leukopenia. After 12 months of recombinant IFN-alpha-2a, 15 cases in progression and 4 with stable disease or partial response received another treatment (either radiometabolic therapy with I131 metaiodobenzylguanidine or polychemotherapy with streptozotocin plus epirubicin).

The use of recombinant IFN-alpha-2a at these doses is well-tolerated and effective in controlling carcinoid syndrome (complete remission plus partial remission, 64%), although it has limited activity on tumor growth inhibition. No definitive data can be given for the other protocol treatments.

PMID: 7693327   [PubMed – indexed for MEDLINE]

Download articolo: Cancer 1993