Chemo-hormone therapy of non-well-differentiated endocrine tumours from different anatomic sites with cisplatinum, etoposide and slow release lanreotide formulation

Abstract

We report the results of a phase II trial in patients with metastatic endocrine tumours from different sites, which aimed to evaluate the anti-tumour activity and toxicity of a cisplatinum and etoposide regimen administered in combination with the somatostatin agonist lanreotide given in slow release formulation. Between January 1999 and November 2003, 27 patients with histological diagnoses of endocrine tumours with different degrees of differentiation, excluding well differentiated carcinoid neoplasms, received intravenous (i.v.) administration of cisplatinum (30 mg m À2 ) and etoposide (100 mg m À2 ) on days 1 -3 and intramuscular administration of 60 mg lanreotide on day 1, in a 21-day cycle. All of the patients were evaluable for toxicity and response. The treatment was very well tolerated as no grade 4 toxicity was observed. Four patients achieved a complete response, six a partial response, 12 experienced disease stabilisation and five disease progression. The average time to progression and to survival were 9 and 24 months respectively. These results suggest that this chemo-hormone therapy regimen is well tolerated and active in patients with non-well differentiated endocrine tumours.

Neuroendocrine Carcinomas of the Gastroenteropancreatic System: A Comprehensive Review

“…The current interpretation of the origin of NENs is that they derive from multi-potent stem cells, which due to genetic alterations (inherited or acquired mutations) progress into cancer. On the basis of their genetic programme and mutations, these multi-potent cells may differentiate into epithelial, glandular, or neuroendocrine cancer type cells and may stop their distinct differentiation programmes at different stages of maturation [ 59 , 60 ]. This is supported by Brenner et al [ 7 ], amongst others, as described in the organ-specific sections.…”

“…Correale et al [ 59 ] have tried combining etoposide and cisplatin with slow release lanreotide. The hypothesis was that lanreotide could sensitise tumour cells to cytotoxic drugs between cycles of chemotherapy, delay the recovery of less chemo-sensitive cells, and synchronise the cell cycle of tumour cells making them more vulnerable to cycle-specific cytotoxic drugs.…”

Downgrading of a G3 Neuroendocrine Tumor to a G2 Tumor: Can First-Line Cytotoxic Chemotherapy Change the Tumor Biology

“…This raises the question if even G3 NETs with a Ki-67 over 20% and less than 55% will benefit from the use of mTOR inhibitors and somatostatin analogs. In a small cohort of 27 heterogeneous patients with poorly differentiated NET, a combination of chemotherapy with slow-release lanreotide showed response rates of up to 37% [ 3 , 12 ]. Gilabert et al [ 13 ] recently published promising results on the use of mTOR inhibitors in combination with somatostatin analogs in a small cohort of patients with NECs of the pancreas (median Ki-67 45%), who refused cytotoxic chemotherapy.…”

Association between time to disease progression end points and overall survival in patients with neuroendocrine tumors

“…These 22 studies included seven controlled and 15 uncontrolled trials, representing 29 unique treatment arms and 2,584 patients (Table 1). 8,9,[11][12][13][14][22][23][24][25][26][27][28][29][30][31][32][33][34][35][36][37] The trials covered a broad range of therapeutics, including octreotide, 8,11,37 everolimus, 13,14,37 interferon-α, 8,34 sunitinib, 9,12 and streptozocin plus 5-fluorouracil. 26,34,36 Four of the controlled studies included placebo arms.…”

“…26,34,36 Four of the controlled studies included placebo arms. 11,12,14,37 Eight of the single-arm studies investigated chemotherapies, [22][23][24][27][28][29]31 and the others studied peptide receptor radionuclide therapy, imatinib, or interferon-γ.…”