Interferon and meta-iodobenzylguanidin combinations in the treatment of metastatic carcinoid tumours

Interferon (IFN) and meta-iodobenzylguanidin (MIBG) are active in metastatic carcinoids. In a phase II study, we evaluated the effect upon diagnostic 131I-MIBG uptake and the clinical response of the combination. 131I-MIBG scintigraphy was performed prior to treatment, after 8 weeks of IFN and after unlabelled MIBG. The tumour over non-tumour (T/NT) ratios were quantitatively determined by comparing counts in the centre of the tumour (liver metastases) with those in an adjacent area of normal liver uptake (T/NT1) and with abdominal background area (T/NT2). The T/NT1 ratio showed an increase of >10% in only four out of 21 patients (19%) after IFN (P = 0.178) and significantly more often in nine out of 18 patients (50%) after unlabelled MIBG (P = 0.016). The absolute uptake in tumour deposits was also increased if compared with the abdominal background (T/NT2: 23% increase after IFN and 83% increase after unlabelled MIBG). The combination produced 91% of patients with stable disease (using World Health Organisation criteria) at computed tomography scan and a biochemical response (a reduction of at least 50% in urinary 5-hydroxyindolacetic acid excretion) in 39%. IFN-alpha did not significantly improve tumour retention of 131I-MIBG. In contrast, unlabelled MIBG significantly improved biodistribution and tumour uptake in 83%. A synergistic effect was not seen.     

Oxaliplatin-based chemotherapy for the treatment of a metastatic carcinoid tumor

Carcinoid tumors are rare and often resistant to chemotherapy agents. Although a slow-growing tumor, patients can have significant morbidity associated with carcinoid syndrome and patients will often die as a result of tumor progression. We report the first case of a patient with a metastatic carcinoid tumor to respond to an oxaliplatin-based regimen. Further studies are needed to validate this observation.     

Evaluation of combined cyclophosphamide and methotrexate therapy in the treatment of metastatic carcinoid tumor and the malignant carcinoid syndrome

Sixteen patients with metastatic carcinoid tumor and the malignant carcinoid syndrome were treated with combined cyclophosphamide and methotrexate therapy in a regimen previously described as highly effective. Toxicity was relatively mild and consisted primarily of leukopenia. One patient experienced some symptomatic benefit and minor reduction in hepatomegaly and 5-hydroxyindoleacetic acid excretion. None met our criteria for an objective response. Combined cyclophosphamide and methotrexate therapy does not appear to offer significant benefit for this disease.     

Heart involvement in metastatic carcinoid disease

Sixteen patients with metastatic carcinoid tumors of ileal or cecal origin were studied in order to evaluate the frequency and degree of cardiac involvement in a nonselected patient group. We have also studied the correlation between plasma hormone levels (e.g., 5-hydroxytryptamine (5-HT) and substance P) and the degree of cardiac involvement. The patients underwent physical examinations, electrocardiograms, chest x-rays, cardiac catheterization, and echocardiography. Plasma levels of 5-HT and substance P were analyzed. Carcinoid heart involvement was found in 3 of 16 patients (19%) but no patient had subjective symptoms associated with heart disease. Four patients (25%) had slight pulmonary hypertension. No left-sided heart lesions were seen. No correlation between blood levels of 5-HT or substance P and heart involvement was found. Eight patients died during the follow-up period, but in none of these was the cause of death cardiac failure. Carcinoid heart disease is not as common in our patients as in patients selected on a cardiological basis described in earlier studies. Echocardiography appears to be the most efficient technique for detection of even subclinical heart involvement and a useful tool for following its progress.     

Complete histological regression of metastatic carcinoid tumour after treatment with octreotide

A 69-year-old woman was admitted with facial flushing, weight loss and intermittent diarrhoea. Urinary 5-hydroxyindole-acetic acid (5-HIAA) level was elevated at 200 micromol/24 h (normal: < 50). Computerized tomography (CT) demonstrated multiple enhancing liver metastases with biopsy proven carcinoid metastases with no evidence of primary tumour at this stage. Octreotide was initiated, resulting in marked improvement in carcinoid symptoms. Nine years later, she presented with abdominal pain and slightly deranged liver function tests. Repeat colonoscopy at this stage, showed an ileal tumour causing impending obstruction, necessitating urgent right hemicolectomy. Histology demonstrated primary carcinoid tumour. She continued on octreotide. Three years later at the age of 81 years, she suffered a fatal haemorrhagic stroke. Autopsy revealed complete regression of hepatic carcinoid metastases.     

Developments in diagnosis and treatment of metastatic midgut carcinoid tumors. A review

Carcinoids are neuroendocrine tumours derived from enterochromaffin cells which are widely distributed in the body and may, therefore, arise from any site. They are traditionally described as originating from the foregut, midgut and hindgut. Localisation in the gastrointestinal tract is the most frequent, among which the appendiceal involvement is often found at laparoscopy for appendicitis and the small bowel is known for the liver metastases with the production of serotonin causing the characteristic carcinoid syndrome with diarrhoea and flushes. The overall incidence of carcinoid disease has increased in the past decades, but whether this is a true increase or due to early detection or better recognition at pathology is not known. The prognosis of metastatic carcinoid tumours has improved during the last decade resulting in a 5 year survival of approximately 50% in the Netherlands. Due to a longer survival, complications such as carcinoid heart disease and new metastatic patterns like skin and bone metastases may become a more important feature in carcinoid disease. New developments are in the field of diagnostics (fine-tuning of the pathology, videocapsule endoscopy to find the primary tumour, positron emission tomography [PET] scanning) and treatment options (radiofrequency ablation, radioactive octreotide, meta-iodobenzylguanidine combinations). The new serum marker of carcinoid, chromogranin A, may play an important role in the follow-up and NT-proBNP for the detection of heart problems. Combining new diagnostic and treatment modalities in metastatic carcinoid patients may result in a better quality of life and a longer survival. The increasing number of therapeutic options and diagnostic procedures requires a multidisciplinary approach focused on tailor-made therapy based on patients' specific conditions preferably in specialised centres and in clinical studies.     

Severe intrapulmonary shunting associated with metastatic carcinoid

A 37-year-old woman with a 10-year history of metastatic carcinoid presented to her oncologist with increased dyspnea. Further evaluation revealed hypoxemia and intrapulmonary vasodilatation. We describe a case of hepatopulmonary-like physiology associated with metastatic carcinoid in a patient with intact liver function. To our knowledge, this is the first documented case of intrapulmonary shunting and hepatopulmonary-like physiology associated with metastatic carcinoid.     

Resected case of carcinoid tumor of the liver metastatic from the breast

Carcinoid tumor metastatic to the liver from the breast is very unusual. We report a rare case in which the patient underwent curative resection for metastatic lesions to the liver. She had undergone a modified radical mastectomy more than 1 year previously for breast cancer. Recently, it was found that plasma levels of carcinoembryonic antigen (CEA) was elevated, and abdominal ultrasonography detected a liver tumor. The patient underwent a lateral segmentectomy of the liver, resulting in normalization of plasma CEA levels. The resected specimen was diagnosed as carcinoid tumor by histological, immunohistochemical, and ultrastructural microscopic studies. Re-examination of the breast tumor proved it to be the primary carcinoid.     

Interventional treatment of the carcinoid syndrome

Liver metastases imply a major problem in patients with carcinoid tumours and hormone overproduction. Patients with distant metastases can undergo resection for potential cure or for symptom palliation. In patients with bilobar liver metastases other interventions are at hand, e.g. local ablation or hepatic arterial embolization. In selected cases liver transplantation can be a treatment alternative. Prior to all interventions patients with midgut carcinoids are protected with somatostatin analogues to reduce hormone secretion. Patients with foregut carcinoids may present special problems with life-threatening release of histamine during interventions.     

Treatment of metastatic carcinoid tumor with dactinomycin or dacarbazine

We studied the effect of two single drugs on patients with metastatic carcinoid tumors. All patients had symptomatic and measurable disease and all had elevations of urinary 5-hydroxy indole acetic acid excretion. Seventeen patients were treated with dactinomycin at a dose of 12-15 micrograms/kg/day for 5 days repeated every 4-5 weeks. One partial response was achieved. Fifteen patients were treated with dacarbazine (DTIC) at a dose of 250 mg/m2/day for 5 days every 4-5 weeks. Two partial responses were achieved. The median times to tumor progression were 10 weeks with dactinomycin and 18 weeks with DTIC. Median survival times were 28 and 47 weeks, respectively. Dactinomycin given by this schedule appears to have only limited activity as a single-agent treatment in malignant carcinoid tumor. DTIC, although showing only a slightly better response rate, perhaps warrants further investigation in view of our more favorable interval to tumor progression and survival experience and in view of this drug's more established activity in the closely related islet cell carcinoma.     

Carcinoid syndrome and carcinoid crisis secondary to a metastatic carcinoid tumour of the lung: a therapeutic challenge

We describe a 53-year-old male patient, with a known history of metastatic carcinoid tumour of the lung, who developed a variety of symptoms of the carcinoid syndrome and subsequently a carcinoid crisis. Although bronchial carcinoid tumours are very rarely associated with symptoms of the carcinoid syndrome, a subset may develop a severe hypersecretory syndrome and exhibit an aggressive behaviour. In cases with excessive tumour load and difficult-to-control hypersecretory syndrome, management by a specialized multidisciplinary team using evidence-based regimens is mandatory to deal with the life-threatening carcinoid crisis, to improve patients' outcome and quality of life.     

Recurrent acute kidney injury associated with metastatic bronchial carcinoid

Acute kidney injury (AKI) is a rare complication of carcinoid syndrome. A 61-year-old man developed carcinoid syndrome 51 months after pneumonectomy for bronchial carcinoid, and 8 episodes of AKI 101 to 118 months after pneumonectomy. Serum chromogranin A and urine 5-hydroxyindoleacetic acid levels were elevated for more than 1 year before AKI occurred. Each episode was characterized by flushing, facial edema, mild diarrhea, necrosis of hepatic metastatic nodules, mild oliguria, hyponatremia, acidosis, hypokalemia, hypomagnesemia and hyperphosphatemia. He did not have elevated urine sodium levels or osmolality, hypotension or hypertension. Plasma levels of dopamine, epinephrine and norepinephrine, measured during a single episode, were markedly elevated. Serum creatinine levels returned to normal after most episodes. Hyponatremia persisted but was more severe during AKI. Elevated plasma levels of vasoactive substances other than 5-hydroxytryptamine, perhaps dopamine or other catecholamines, could explain recurrent AKI. The natriuretic effect of elevated plasma dopamine levels could explain chronic hyponatremia.