Growth factor-receptor pathway interfering treatment by somatostatin analogs and suramin: Preclinical and clinical studies

Klijn, Jan G.M.; Setyono-Han, Buddy; Bakker, G.H.; Burg, M.E.L. van der; Bontenbal, M.; Peters, H. A.; Siewerts, A.M.; Berns, P.M.J.J.; Foekens, John A.

doi:10.1016/0960-0760(90)90471-v

Cited by 22 publications

(15 citation statements)

References 25 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…This problem will be resolved by the application of depot preparations of somatostatin analogues that are increasingly available. Furthermore continuous administration of drugs is generally more effective than daily injections as demonstrated for octreotide (Klijn et al, 1990b;Weckbecker et al, 1994). In our pilot study, the patients treated with the combination therapy showed progressive disease from start of treatment less frequently and a longer progression-free survival, but the numbers are undoubtedly too small for definite conclusions and our results have to be confirmed by other much larger studies.…”

Section: Anti-tumour Effectsmentioning

confidence: 99%

Feasibility, endocrine and anti-tumour effects of a triple endocrine therapy with tamoxifen, a somatostatin analogue and an antiprolactin in post-menopausal metastatic breast cancer: a randomized study with long-term follow-up

Bontenbal

Foekens²,

Lamberts³

et al. 1998

Br J Cancer

View full text Add to dashboard Cite

Summary Suppression of the secretion of prolactin, growth hormone and insulin-like growth factor 1 (IGF-1) might be important in the growth regulation and treatment of breast cancer. Because oestrogens may counteract the anti-tumour effects of such treatment, the combination of an anti-oestrogen (tamoxifen), a somatostatin analogue (octreotide) and a potent anti-prolactin (CV 205-502) might be attractive. In this respect, we performed a first exploratory long-term study on the feasibility of combined treatment and possible clear differences in endocrine and anti-tumour effects during such combined treatment vs standard treatment with tamoxifen alone. Twenty-two post-menopausal patients with metastatic breast cancer (ER and/or PR positive or unknown) were randomized to receive either 40 mg of tamoxifen per day or the combination of 40 mg of tamoxifen plus 75 ig of CV 205-502 orally plus 3 x 0.2 mg of octreotide s.c. as first-line endocrine therapy. An objective response was found in 36% of the patients treated with tamoxifen alone and in 55% of the patients treated with combination therapy. Median time to progression was 33 weeks for patients treated with tamoxifen and 84 weeks for patients treated with combination therapy, but the numbers are too small for hard conclusions. There was no difference in overall post-relapse survival between the two treatment arms. With respect to the endocrine parameters, there was a significant decrease of plasma IGF-1 levels in both treatment arms, whereas during combined treatment plasma growth hormone tended to decrease and plasma prolactin levels were strongly suppressed; in some patients insulin and transforming growth factor a (TGF-a) decreased during the triple therapy. Although there was no significant difference in mean decrease of plasma IGF-1 levels between the two treatment arms, combined treatment resulted in a more uniform suppression of IGF-1. Therefore, the addition of a somatostatin analogue and an anti-prolactin may potentially enhance the efficacy of anti-oestrogens in the treatment of breast cancer owing to favourable endocrine and possible direct anti-tumour effects. Large phase IlIl trials using depot formulations (to increase the feasibility) of somatostatin analogues are warranted to demonstrate the potential extra beneficial anti-tumour effects of such combination therapy.

show abstract

Section: Anti-tumour Effectsmentioning

confidence: 99%

Feasibility, endocrine and anti-tumour effects of a triple endocrine therapy with tamoxifen, a somatostatin analogue and an antiprolactin in post-menopausal metastatic breast cancer: a randomized study with long-term follow-up

Bontenbal

Foekens²,

Lamberts³

et al. 1998

Br J Cancer

View full text Add to dashboard Cite

show abstract

“…12 Chemically it is a polysulphonated napthyl urea and has been used long since for the treatment of trypanosomiasis. It is a potent inhibitor of PDGF, IGF, bFGF 13,14 and VEGF, 15 which also brings it in focus as an antiangiogenic compound.…”

mentioning

confidence: 99%

Suramin augments the antitumor and antimetastatic activity of pentoxifylline in B16F10 melanoma

Dua

Ingle

Gude

2007

Intl Journal of Cancer

View full text Add to dashboard Cite

Rapid tumor growth and metastasis are 2 major problems associated with treatment of malignant melanoma. Therefore, drugs that can intervene these processes are of clinical importance. Pentoxifylline (PTX), a methyl xanthine derivative, has been shown to inhibit B16F10 melanoma tumor growth and metastasis. We hypothesized that suramin when combined with PTX enhances its antineoplastic effects, which we have examined using the B16F10 mouse melanoma model. Suramin in simultaneous or sequential combination potentiated the cytotoxic effects of PTX on B16F10 cells. PTX arrested cells in the G0-G1 phase and suramin augmented the effects. Both the drugs inhibited F10 adhesion to laminin, matrigel and collagen type IV and showed enhanced inhibition in combination The combination also demonstrated significantly higher inhibition in cell motility (p 5 0.002) and invasion through matrigel (p 5 0.005) as compared to the single agents. Suramin synergized with PTX in its effects on secretion of MMP-9 gelatinase. DBA2/J mice implanted with intradermal B16F10 tumor were used as a model to study tumor growth. Animals were intratumorally treated with 50 mg/kg of PTX, 10 mg/kg of suramin and their combinations. Simultaneous administration of the drugs inhibited tumor growth by 5-to 6-folds. Tumor growth was completely blocked in sequential regimen with regression in some cases. The number and size of metastatic nodules on lung was also reduced significantly by the combination treatment. In conclusion, the novel combination of PTX and suramin has synergistic antitumor and antimetastatic activity in B16F10 melanoma and may be a promising approach in treatment of patients suffering from malignant melanoma. ' 2007 Wiley-Liss, Inc.Key words: pentoxifylline; suramin; B16F10 melanoma; metastasis; combination therapy Malignant melanoma is the deadliest form of skin cancer, and its incidence has shown a 6-fold increase since the past 2 to 3 decades.1 There is no standard treatment for patients with metastatic melanoma. Treatment options include the surgical resection of isolated metastases, therapy with dacarbazine, and immunotherapy. However, response rates associated with these measures range between 15 and 20%, and hence there is an urgent need for the development of new therapies. The success of antimetastatic therapy depends on inhibition of diverse stimuli produced by the tumor and its microenvironment while limiting overall toxicity. Thus it has been suggested that a combination of antimetastatic compounds may be more effective than monotherapies.In our earlier reports we have demonstrated that pentoxifylline (PTX), a methyl xanthine derivative inhibits B16F10 melanoma solid tumor growth and metastasis to lung, 3 which is mediated via its inhibitory action on cell adhesion, MMP-9 and -2 secretion, 4 and tumor angiogenesis.5 PTX has been used to enhance tumor sensitivity to both radiation 6 and alkylating agents 7 because of its antioxidant nature and its property to abrogate the G2-M checkpoint, respectively. It has also been reporte...

show abstract

“…In our experience the non-specific growth factor antagonist suramin caused growth inhibition in several human breast cancer cell lines in vitro, but low concentrations of this drug can stimulate growth in some of them, especially EGF-R-rich tumor cell types (77). In a few heavily pretreated patients with metastatic breast cancer we observed no objective response (76). However, more specifically acting growth factor antagonists (not also inhibiting growth inhibitory growth factors) are needed.…”

Section: Therapies Interfering With Growth Factor-mediated Pathwaysmentioning

confidence: 75%

“…Potentially, the administration of growth inhibitory growth factors (TGF-/I) or analogues might inhibit breast cancer growth, when sufficient amounts of these agents become available. Growth factor antagonists can inhibit tumor growth in vitro and in vivo by blocking growth factor receptors for their respective growth factors (76,77). In our experience the non-specific growth factor antagonist suramin caused growth inhibition in several human breast cancer cell lines in vitro, but low concentrations of this drug can stimulate growth in some of them, especially EGF-R-rich tumor cell types (77).…”

Section: Therapies Interfering With Growth Factor-mediated Pathwaysmentioning

confidence: 93%

Novel Endocrine Therapies in Breast Cancer

et al. 1996

Self Cite

View full text Add to dashboard Cite

Growth factor-receptor pathway interfering treatment by somatostatin analogs and suramin: Preclinical and clinical studies

Cited by 22 publications

References 25 publications

Feasibility, endocrine and anti-tumour effects of a triple endocrine therapy with tamoxifen, a somatostatin analogue and an antiprolactin in post-menopausal metastatic breast cancer: a randomized study with long-term follow-up

Feasibility, endocrine and anti-tumour effects of a triple endocrine therapy with tamoxifen, a somatostatin analogue and an antiprolactin in post-menopausal metastatic breast cancer: a randomized study with long-term follow-up

Suramin augments the antitumor and antimetastatic activity of pentoxifylline in B16F10 melanoma

Novel Endocrine Therapies in Breast Cancer

Contact Info

Product

Resources

About