Relapse prevention by Immunocyanin

Meerschnecken - pixabay
Meerschnecken - pixabay

For some years there are for patients in whom the instillation of mitomycin or BCG, for example, was unsuccessful or an intolerance showed alternative treatment option with Immunocyanin.

The benefits of Immunocyanin the superficial bladder carcinoma

Unfortunately this drug is not yet approved in Germany and therefore also listed not in the Red List (medication list Germany), although the treatment is quite be prescribed when indicated in individual cases and is taken over by the health insurance companies in providing adequate justification for the urologist (efficiency principle gem .§§ 12 para. 1.70 para. 1 SGB V). In particular, the application must be appropriate and necessary. This is due in particular when other installation therapy were unsuccessful or had to be canceled due to incompatibility and repeatedly Op’s are required because of the recurrence neoplasms, or the risk that a recurrent tumor enters a less favorable stage.

Therapy with Immunocyanin (product name: IMMUCOTHEL®), lasts a year similar to the therapy with BCG, but has far fewer side effects.

Here is a suggestion of a letter giving reasons for the urologist in relation to the insurance company:

Justification for the benefit of IMMUCOTHEL® the
superficial bladder carcinoma.

For submission to health insurance

IMMUCOTHEL® as an effective ingredient Immunocyanin, a stable form of the blood pigment keyhole limpet hemocyanin (KLH) of sea snail Megatura crenulata.

Preclinical investigations:

IMMUCOTHEL® resulted in animal studies and preclinical studies by instillation into the bladder to an activation of macrophages and T lymphocytes and humoral immune response. In the top layer of Bladder-epitels there is a significant increase of T-helper cells, an increase in the CD4 / CD (quotient, an increased release of interferon-α and other cytokines The cytokines interleukin-1α and β increased by IMMUCOTHEL® instillation excreted in the urine, indicating a strong macrophage activation. (Dome 1984 Munder 1986 Recker et al.1989, Linn et al. 1997 Jurinčić et al 1989. Jurinčić-Winkler et al. 1995). The glycoprotein KLH contains Gal (β1 -3) -. Gal NAC-containing oligosaccharides This structure corresponds to the Thomsen-Friedenreich antigen, increasingly expressed freely on bladder carcinoma cells but not on normal Blasenepitel (Wirguin et al 1995) The result is the immunization of T… lymphocytes with a KLH-specific immune response against bladder cancer cells.

Clinical studies:

Superficial bladder tumors (PTA, pT1, G1-G2) have transuretraler after resection (TUR) is a high recurrence rate of up to over 70%. To reduce the rate of recurrence instillations of adriamycin or mitomycin C, thiotepa or BCG over a period of one year are performed postoperatively.

Intravesical chemotherapy was studied in a total of 17 studies of 2,331 patients. In this case, an advantage for Adriamycin (30-61% relapse in 17-29 months) Mytomycin C gave (16-83% relapse in 12-65 months) Ethoglucid (7-81% recurrence in 6-60 months) and thiotepa (24 -65% recurrence in 24-60 months).

Any adjuvant therapies were but better than TUR alone (Lamb et al., 1992, Rübben et al. 1997 Rübben et al., 1990, Otero-Mauricio et al. 1992).

Side effects of chemotherapy are intravesical heavy Chemozystitis in 20-38% of patients (Rübben et al., 1990, Otero-Mauricio, et al. 1992).

An improvement in the prevention of relapse is the opposite, the instillation of BCG. There was a reduction of recurrence by 20-30% compared with TUR and to 19-41% compared with chemotherapy after TUR. After BCG the recurrence rate is 11-75% at 6-67 months of observation (Rübben et al. 1997). Side effects of this therapy are available in up to 91% cystitis, often severe, in 40% fever, 3% BCG sepsis with a total so far 8 deaths after BCG instillation (Orihuela et al.1987, IZES et al. 1993 Lammetal. 1992).

Instillation with IMMUCOTHEL®:

As early as 1974 (Olsson et al. 1974) was described in bladder tumors efficacy of subcutaneously administered KLH.

The previously conducted prospective randomized studies with IMMUCOTHEL® show a statistically significant superiority compared to mitomycin C (Jurinčić et al. 1988), an equally good effect as Ethoglucid (flame et al., 1990, Flash et al., 1991, Flash et al. 1994) , The effect of IMMUCOTHEL® is comparable to that of BCG (Kälble et al. 1991).

The side effects of IMMUCOTHEL® to 572 documented patients grade I fever in 3%, 6% and cystitis in sporadically (<1%) feeling of pressure, pain, urinary urgency and increased -γGT and GPT.


The instillation prophylaxis of superficial bladder-carzinoms is today a recognized adjuvant method with the aim of preventing recurrence after TUR. Given the approximately same effect, the rate of side effects for the rash should be for the use of IMMUCOTHEL®.Especially the chemotherapy and BCG regularly occurring, severe cystitis is stressful for patients in the highest degree, especially as the total treatment lasts one year. You should also keep in mind that cytostatics, which are instilled into the bladder, be issued without metabolized in the environment.

After all, are mutagenic and carcinogenic substances so that cytostatic agents. BCG is a live vaccine, which is potentially infectious.IMMUCOTHEL® does not have these undesirable characteristics and therefore should have priority over other materials. In Holland IMMUCOTHEL® approved since 1998 for the indication of superficial bladder carcinoma, in Austria since of 2002.


  • Klippel KF: Unspecified intralesional immunotherapy in bladder carcinoma. In: Huland H, Klosterhalfen (eds): treatment and prevention of recurrence of superficial bladder cancer. Georg Thieme, Stuttgart / New York 1984th
  • Munder PG: Studies o­n the antitumoral effects of keyhole-limpet hemocyanin (KLH) in-vitro and in-vivo. Present Status of non-toxic concepts in cancer. Proc. Int. Symposium Nonnweiler/Trier 1986.
  • Recker F, Rübben H: Variation of the immunsystem by cyclosporin and keyhole-limpet hemocyanin. Are there effects o­n chemically induces bladder carcinoma? Urol. Int, 1989;. 44:77-80.
  • JF Linn, Rübben H: keyhole limpet hemocyanin immunotherapie for chemically induced bladder cancer: systemic verses topical administration. Brit.J. Urol. 1997; 80: 158.
  • Jurinčić CD, mackerel W, Klippel KF, Markl J): Immunohistochemical study of bladder biopsies after immunotherapy of superficial bladder cancer with keyhole limpet hemocyanin (KLH). In: Boots T, Borcher H (eds) Immucothel Workshop II, Avignon 1988 biosynposia Stuttgart, 1989; 45-55.
  • Jurincic-Winkler CD, Gallali H, Alvarez-Mon M et al.: Urinory interlokin 1α-levels are increased by intraversical instillation with keyhole-limpet hemocyanin and patients with superficial transitional cell carcinoma of the bladder. Eur. Urol. 1995; 28: 334-339.
  • I Wirguin, Suturkova L-Milosevic, Briani C et al .: Keyhole limpet hemocyanin contains-Gal (β1-3) -Gal NAC determinants that are cross-reactive with T-antigen. Cancer Immunol. Immunotherapie 1995; 40: 307-310.
  • Lamm DL, Griffith G, Pettit LL et al.: Current perspectives o­n diagnoses and treatment of superficial bladder cancer. Urology 1992; 39:301-308.
  • Rübben H. Deutz F, Hofstädter F et al.: Treatment of low and high risk superficial bladder tumors (SBT). In: Frohmüller HGW, Wirth MP (eds): Current Status and future trends. Wiley-Liss Inc. New York 1990.
  • Rübben H, Otto T: Harnblasenkarzmome. In: Rübben H (ed): Uroonkologie Springer Berlin, Heidelberg, New York 1997th
  • Mauricio Otero-G, Franco-Manzano R-Trevijano Ardanza A et al: Immunocyanina des intravesical treatment in superficial tumors vegiga. Comparative study aonco-tiotepa front. Manuskript 1992.
  • Olsson CA, Chute R, Rao N; Immunologie reduction of bladder cancer recurrance rate. J.Urol. 1974; III: 173-176.
  • Orihuela E, Herr HW, Pinsky CM et al: Toxicity of intravesical BCG and ist management in patiens with superficial bladder tumors. Cancer 1987, 60: 326-333.
  • Izes JK, Bihrle W, Thomas CB: Corticosteroid-associated fatal mycobacterial sepsis occuring 3 years after instillation of intravesical bacillus Calmette-Guerin. J. Urol. 1993; 150: 1498-1500.
  • Lamm DL, Van der Meijden APM, Morales A et al.: Incidence and treatment of complications of bacillus Calmette-Guerin intravesical therapy and superficial bladder cancer. J. Urol; 1992; 147: 596-600
  • Jurincic CD, Engelmann V, Gasch J et al.: Immunotherapy in bladder cancer with keyhole-limpet hemocyanin: a randomized study. J. Urol. 1988; 139: 723-726.
  • Flamm J, Bucher A, Höltl W et al.: Recurrent superficial transitional cell carzinoma of the bladder: adjuvant topical chemotherapy versus immunotherapy . A prospective randomized trial. J. Urol. 1990; 144:260-263.
  • Flamm J, Bucher A: Adjuvant topical chemotherapy versus immunotherapy and primary superficial transitional cell carzinoma of the bladder. Brit. J. Urol. 1991; 67:70-73.
  • Flash J, Donner G, Bucher A et al .: Topical immunotherapy (KLH) versus chemotherapy
  • (Ethoglucid) in the prevention of recurrence of superficial bladder cancer. Urologist (A) 1994; 33: 138-143.
  • Kälble T, K Mohring, Ikinger U et al .: Intravesical Prevention of relapse of superficial bladder cancer with BCG and KLH. A prospective randomized study. Urologist (A), 1991; 30: 118-121

Prof. Dr. med. K. Schumacher
chief physician retired
specialist in internal medicine,
hematology and internal oncology
70839 Gerlingen

Treatment (therapy) of superficial bladder cancer


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