An Assessment of the Current Use of Human Interferons in Therapy of Urological Cancers

Purpose: To assess the current treatment of metastatic renal cell carcinoma, focusing on medical treatment options. Material and Methods:The most important recent publications have been selected after a literature search employing PubMed using the search terms: advanced and metastatic renal cell carcinoma, anti-angiogenesis drugs and systemic therapy; also significant meeting abstracts were consulted. Results: Progress in understanding the molecular basis of renal cell carcinoma, especially related to genetics and angiogenesis, has been achieved mainly through of the study of von Hippel-Lindau disease. A great variety of active agents have been developed and tested in metastatic renal cell carcinoma (mRCC) patients. New specific molecular therapies in metastatic disease are discussed. Sunitinib, Sorafenib and Bevacizumab increase the progression-free survival when compared to therapy with cytokines. Temsirolimus increases overall survival in high-risk patients. Growth factors and regulatory enzymes, such as carbonic anhydrase IX may be targets for future therapies. Conclusions: A broader knowledge of clear cell carcinoma molecular biology has permitted the beginning of a new era in mRCC therapy. Benefits of these novel agents in terms of progression-free and overall survival have been observed in patients with mRCC, and, in many cases, have become the standard of care. Sunitinib is now considered the new reference first-line treatment for mRCC. Despite all the progress in recent years, complete responses are still very rare. Currently, many important issues regarding the use of these agents in the management of metastatic renal cancer still need to be properly addressed.

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“…However, immunotherapy produced objective response rates in the range of 10-20% with median stable disease (SD) of 3-16 months (13).…”

Section: Cytokinesmentioning

confidence: 99%

Metastatic renal cell carcinoma management

et al. 2009

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“…Observed grade II and III toxicity is given in Table IV obtained from pooled data is about 17% (Krown, 1987;Muss, 1988;Horoszewicz et al, 1989;De Mulder et al, 1991). (Geboers et al, 1988).…”

Section: Toxicitymentioning

confidence: 99%

EORTC (30885) randomised phase III study with recombinant interferon alpha and recombinant interferon alpha and gamma in patients with advanced renal cell carcinoma

Mulder

Oosterhof²,

Bouffioux³

et al. 1995

Br J Cancer

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In the treatment of renal cell carcinoma both complete (CRs) and partial remissions (PRs) have been obtained using recombinant (r) interferon alpha (IFN-alpha), with response rates ranging from 0 to 31% (mean 16%). rIFN-gamma is a potent immunostimulating agent, but the clinical experience of its use is limited and results are conflicting. In a phase II study with the combination of rIFN-alpha 2c (Boehringer Ingelheim) and rIFN-gamma (Genentech, supplied by Boehringer Ingelheim) in 31 eligible patients, a response rate of 25% was recorded. Based on this observation a randomised phase III study was initiated to investigate the possible advantage of the addition rIFN-gamma to rIFN-alpha 2c treatment. Treatment consisted of rIFN-alpha 2c 30 micrograms m-2 = 10 x 10(6) IU m-2 s.c. twice weekly in arm A and the same dose of rIFN-alpha combined with rIFN-gamma 100 micrograms m-2 = 2 x 10(6) IU m-2 in arm B. Eligibility criteria included documented progression of disease; patients with bone lesions only and overt central nervous system metastases were excluded. Between November 1988 and September 1990, 102 patients were entered into the study. An interim analysis showed a response in 7/53 (13%) patients (two CRs and five PRs) in the rIFN-alpha 2c monotherapy arm and in 2/45 (4%) (one CR and one PR) patients in the combination arm. This difference was not statistically significant (P = 0.17). The probability of missing an eventual 10% advantage for the combination is 0.001. The numbers are insufficient to rule out a negative effect of the addition of rIFN-gamma. The dose intensity of IFN-alpha 2c for the two treatment arms was the same. The addition of rIFN-gamma does not improve the response rate of rIFN-alpha 2c monotherapy. A possible detrimental effect cannot be excluded.

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“…This compares survival of 63 metastatic renal cell cancer patients receiving tamoxifen only vs 65 patients (Horoszewicz and Murphy, 1989;Jeal and Goa, 1997) receiving tamoxifen plus interleukin 2/alpha interferon for 6 weeks followed by maintenance treatment for 5 days every 4 weeks for up to 12 months (Henriksson et al, 1998 . The answer must be a resounding yes, and it could be said that there is a case for the drug companies involved to almost feel a moral obligation to encourage recruitment, given the continued ongoing scepticism about cytokine therapy.…”

mentioning

confidence: 99%

“…However, even if this trial does succeed, as the paper of Henriksson et al (1998) indicates, there is a need for new approaches to working out dosages and duration of treatment with biological agents that have bell-shaped dose-response curves. Even for alpha interferon 20 years after it was first used, it is far from clear what is the optimum dose (Horoszewicz and Murphy, 1989). There has been some attempt to investigate this using in vitro studies on bladder cancer cell lines.…”

mentioning

confidence: 99%

Are cytokine responses in renal cell cancer the product of placebo effect of treatment or true biotherapy? What trials are needed now?

Oliver

1998

Br J Cancer

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An Assessment of the Current Use of Human Interferons in Therapy of Urological Cancers

Cited by 121 publications

References 48 publications

Metastatic renal cell carcinoma management

Metastatic renal cell carcinoma management

EORTC (30885) randomised phase III study with recombinant interferon alpha and recombinant interferon alpha and gamma in patients with advanced renal cell carcinoma

Are cytokine responses in renal cell cancer the product of placebo effect of treatment or true biotherapy? What trials are needed now?

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