Gastrointestinal neuroendocrine tumors treated with high dose octreotide-LAR: A systematic literature review

Table 4 Expert clinical opinion statements on use of octreotide long-acting repeatable > 30 mg/mo

Ref.	Quoted expert clinical opinion
Chadha et al[12] 2009	p 4130: "Our experience and those of others have shown that S-LAR can provide disease control to prolong time needed for liver- directed therapies and systemic therapies. Dose escalation provides an opportunity to spare patients from morbidities associated with these procedures and systemic therapy."
Colao et al[8] 2010	p 290: “The dosages of SSAs currently used are probably insufficient to determine control of hormone secretion and tumor growth both in acromegaly and NETs.”
Costa et al[13] 20061	"Dose increase with octreotide LAR should be offered to those patients who progress after achieving a first objective response with SS analogues."
Oberg et al[9] 2004	p 970: "As a general rule, if the total IR dose is 200-600 μg/d, LAR 20 mg should be tried, and if total IR dose is 750-1500 μg/d, LAR 30 mg should be tried. The LAR doses range from 20 to 60 mg/28 d. Supplementary administration with the IR form of octreotide in patients escaping anti-secretory response is often required during long-term treatment with LAR. If it is necessary to give the patient rescue doses of IR octreotide three or four times per week, increase the LAR dose to 30 mg/4 wk, or reduce the interval between administrations of the depot formulation (e.g., 20 mg/3 wk). Furthermore, the temporal occurrence of hypersecretion during the 4-week dosing interval should be considered. For example, if the rescue s.c. therapy is required during the week before the next injection of LAR, then a reduction of the dosing interval by 1 wk is advisable. On the other hand, if the need for rescue medication occurs sporadically throughout the month then increasing the dose stepwise by 10 mg/mo up to 60 mg/mo should be tried. Doses of LAR > 60 mg/mo are rarely of added value."
Strosberg et al[2] 2013	p 5: "In patients with uncontrolled secretory symptoms, increasing the dose/frequency of SSAs is appropriate (median rating, 8), particularly among patients who had previously responded to a lower dose. The panel considered dose escalations of octreotide LAR up to 60 mg/4 wk (median rating, 7) or up to 40 mg/3 wk (median rating, 7) to be reasonable adjustments for refractory carcinoid syndrome. Increasing the dose/frequency of SSAs may be considered in patients with radiographic progression, particularly those whose disease was previously stabilized at a lower dose. The panel considered an increase in dose/frequency up to 40 mg/3 or 4 wk to be reasonable (median rating: 4-5.5). There is a lack of evidence that increasing the dose/frequency of SSAs slows radiographic progression."
Strosberg et al[22] 20131	“Above label dosing of octreotide LAR is common in NCCN institutions. The primary indication is refractory carcinoid syndrome.”
Xu et al[23] 20121	"Our analyses showed that patients frequently required the escalation of octreotide LAR dose during their course of illness. A substantial number of patients required doses greater than the FDA approved dose of 30 mg/mo."
Yao et al[10] 2008	p 338: "Although octreotide has proven to be a safe and efficacious drug for carcinoid syndrome, it nonetheless can cause adverse events including steatorrhea, cholelithiasis, and hyperglycemia. Until conclusive data from randomized studies are available to show that octreotide has a disease-stabilizing effect and at what does this effect occurs in humans, we advocate titrating the octreotide LAR dose according to symptoms rather than to an arbitrary blood level."

¹Conference abstract. NCCN: National Comprehensive Cancer Network; NETs: Neuroendocrine tumors; S-LAR: Octreotide long-acting repeatable; FDA: Food and Drug Administration; SSAs: Somatostatin analogues.