Researchers affiliated with the Eastern Cooperative Oncology Group have reported that a Zanosar (streptozocin) regimen improved survival of patients with advanced carcinoid tumors compared to a doxorubicin containing regimen. The details of this randomized trial appeared in the August 1, 2005, issue of the Journal of Clinical Oncology.

Carcinoid tumors originate from neuroendocrine cells throughout the body and are capable of producing various active peptides. Carcinoid tumors can be slow growing or very aggressive, but the five year survival for all patients is approximately 70%. Management of carcinoid tumors requires an understanding of the disease process and a multimodality treatment approach involving surgery, radiation therapy, chemotherapy and endocrine suppression. The introduction of the long-acting somatostatin analogue Sandostatin® (octreotide) has resulted in significant advances in palliation and in controlling carcinoid syndromes. However, advanced carcinoid tumors are incurable and palliation is the goal. Most current therapies have low activity and high toxicity. It may be important for symptom control to surgically remove all possible lesions even if this is not curative before chemotherapy or Sandostatin treatment. Chemotherapy response rates are low and some of the agents studied include 5-fluorouracil, BiCNU® (carmustine), CeeNU® (lomustine), doxorubicin, dacarbazine and Zanosar.

In the present study 179 patients with advanced symptomatic carcinoid who had not received prior chemotherapy and did not have significant heart or renal disease were randomly allocated to receive a regimen of fluorouracil/doxorubicin (FU/DOX) or fluorouracil/Zanosar (FU/STZ). After treatment failure patients were treated with dacarbazine (DTIC). An additional 73 patients were assigned to receive DTIC, FU/DOX or FU/STZ based on the presence of heard or renal disease or prior treatment with FU, DOX or STZ. Outcomes of the randomized trial are shown in Table 1.

Table 1: Comparison of FU/DOX and FU/STZ Regimens in Advanced Carcinoid Patients

In the crossover group of 61 patients the overall response rate to DTIC was 8.2% with disease stabilization in 11% and a median survival of 12 Months. Outcomes were similar for the patients assigned to receive either FU/DOX or FU/STZ because of prior history of treatment or organ dysfunction. These authors stated that hematologic toxicities were the most common side effects following FU/DOX or FU/STZ. Toxicities were generally less for DTIC. There were more cases of renal toxicity in patients receiving STZ. These authors concluded that all three regimens had modest activity for treatment of advanced carcinoid. The improvement in survival with STZ makes this an option for selected patients with good renal function.

Comments: This article is a good review of the difficulties of treating patients with advanced carcinoid tumors.

Reference: Sun W, Lipsitz S, Catalano P, et al. Phase II/III study of doxorubicin fluorouracil compared with streptozocin with fluorouracil or dacarbazine in the treatment of advanced carcinoid tumors; Eastern Cooperative Oncology Group Study E1281. Journal of Clinical Oncology . 2005;23:4897-4904.