Bacillus Calmette-Guérin (BCG) intravesicular chemotherapy in bladder cancer

From HemOnc.org - A Hematology Oncology Wiki
Jump to: navigation, search

Regimen variant #1, low-dose (27 mg)

Study Evidence Comparator Comparative Efficacy
Ojea et al. 2007 (CUETO study 95011) Phase III (E-esc) 1. Mitomycin Superior DFS
2. Very-low-dose BCG Seems not superior

Preceding treatment

  • TURBT, within 14 to 21 days

Immunotherapy, induction

6-week course, then proceed to additional therapy

Immunotherapy, continuation

14-day cycle for 6 cycles

Regimen variant #2, intravesical (81 mg) & percutaneous, with maintenance therapy

Study Evidence Comparator Comparative Efficacy
Lamm et al. 2000 (SWOG 8507) Phase III (E-RT-esc) Intravesical & percutaneous BCG, without maintenance therapy Superior RFS

Immunotherapy, induction

  • Bacillus Calmette-Guérin (Connaught strain) 81 mg in 50.5 mL saline suspension is created and administered as follows:
    • 50 mL (~80.2 mg) intravesicularly, and delivered through a catheter into the bladder once per day on days 1, 8, 15, 22, 29, 36. Patients lie on their abdomen for 15 minutes and retain the BCG suspension for up to 2 hours if possible.
    • 0.5 mL (~0.8 mg) applied once per day on days 1, 8, 15, 22, 29, 36 to the inner thigh, which is first cleaned with alcohol. For percutaneous administration, the skin is punctured 3 times with a sterile 28 gauge needle. Each subsequent administration alternates between thighs (i.e. left thigh on one week, right thigh the next week, left thigh the week after, etc.).

6-week course, then proceed to maintenance therapy

Immunotherapy, maintenance

The authors were a bit unclear about the schedule of maintenance therapy. This is our best interpretation of how the schedule was described.

  • Bacillus Calmette-Guérin (Connaught strain) 81 mg in 50.5 mL saline suspension is created and administered as follows:
    • 50 mL (~80.2 mg) intravesicularly, and delivered through a catheter into the bladder once per day on days 1, 8, 15. Patients lie on their abdomen for 15 minutes and retain the BCG suspension for up to 2 hours if possible.
    • 0.5 mL (~0.8 mg) applied once per day on days 1, 8, 15 to the inner thigh, which is first cleaned with alcohol. For percutaneous administration, the skin is punctured 3 times with a sterile 28 gauge needle. Each subsequent administration alternates between thighs (i.e. left thigh on one week, right thigh the next week, left thigh the week after, etc.).

3-week courses; each course is given at 3 months, 6 months, 12 months, 18 months, 24 months, 30 months, and 36 months after the start of induction therapy

Regimen variant #3, intravesical (81 mg) & percutaneous, without maintenance therapy

Study Evidence Comparator Comparative Efficacy
Lamm et al. 2000 (SWOG 8507) Phase III (C) Intravesical & percutaneous BCG, with maintenance therapy Inferior RFS

Immunotherapy

  • Bacillus Calmette-Guérin (Connaught strain) 81 mg in 50.5 mL saline suspension is created and administered as follows:
    • 50 mL (~80.2 mg) intravesicularly, and delivered through a catheter into the bladder once per day on days 1, 8, 15, 22, 29, 36. Patients lie on their abdomen for 15 minutes and retain the BCG suspension for up to 2 hours if possible.
    • 0.5 mL (~0.8 mg) applied once per day on days 1, 8, 15, 22, 29, 36 to the inner thigh, which is first cleaned with alcohol. For percutaneous administration, the skin is punctured 3 times with a sterile 28 gauge needle. Each subsequent administration alternates between thighs (i.e. left thigh on one week, right thigh the next week, left thigh the week after, etc.).

6-week course

Regimen variant #4, intravesical (120 mg) & percutaneous, with maintenance therapy

Study Evidence Comparator Comparative Efficacy
Lamm et al. 1991 (SWOG 8216) Phase III (E-RT-switch-ooc) Doxorubicin Seems to have superior DFS

Immunotherapy, induction

  • Bacillus Calmette-Guérin (Connaught strain) 120 mg (3 vials) in 50.5 mL saline suspension is created and administered as follows:
    • 50 mL (~120 mg) intravesicularly, and delivered through a catheter into the bladder once per day on days 1, 8, 15, 22, 29, 36. Patients retain the BCG suspension for up to 2 hours if possible.
    • 0.5 mL (~1.2 mg) applied once per day on days 1, 8, 15, 22, 29, 36 to the upper part of the inner thigh

6-week course, then proceed to maintenance therapy

Immunotherapy, maintenance

  • Bacillus Calmette-Guérin (Connaught strain) 120 mg (3 vials) in 50.5 mL saline suspension is created and administered as follows:
    • 50 mL (~120 mg) intravesicularly once on day 1. Patients retain the BCG suspension for up to 2 hours if possible.
    • 0.5 mL (~1.2 mg) applied once on day 1 to the upper part of the inner thigh

Given at 3 months, 6 months, 12 months, 18 months, and 24 months

Regimen variant #5, 150 mg

Study Evidence Comparator Comparative Efficacy
Martínez-Piñeiro et al. 1990 Phase III (E-switch-ooc) 1. Doxorubicin
2. Thiotepa
Superior RFS

Note: details are very sparse in the abstract and this is probably only of historic interest.

Immunotherapy

References

  1. Martínez-Piñeiro JA, Jiménez León J, Martínez-Piñeiro L Jr, Fiter L, Mosteiro JA, Navarro J, García Matres MJ, Cárcamo P. Bacillus Calmette-Guérin versus doxorubicin versus thiotepa: a randomized prospective study in 202 patients with superficial bladder cancer. J Urol. 1990 Mar;143(3):502-6. link to SD article contains partial protocol PubMed
  2. SWOG 8216: Lamm DL, Blumenstein BA, Crawford ED, Montie JE, Scardino P, Grossman HB, Stanisic TH, Smith JA Jr, Sullivan J, Sarosdy MF, Crissman JD, Coltman CA. A randomized trial of intravesical doxorubicin and immunotherapy with bacille Calmette-Guérin for transitional-cell carcinoma of the bladder. N Engl J Med. 1991 Oct 24;325(17):1205-9. link to original article PubMed
  3. SWOG 8507: Lamm DL, Blumenstein BA, Crissman JD, Montie JE, Gottesman JE, Lowe BA, Sarosdy MF, Bohl RD, Grossman HB, Beck TM, Leimert JT, Crawford ED. Maintenance bacillus Calmette-Guérin immunotherapy for recurrent TA, T1 and carcinoma in situ transitional cell carcinoma of the bladder: a randomized Southwest Oncology Group Study. J Urol. 2000 Apr;163(4):1124-9. link to original article contains verified protocol PubMed
  4. Meta-analysis: Sylvester RJ, van der Meijden AP, Lamm DL. Intravesical bacillus Calmette-Guérin reduces the risk of progression in patients with superficial bladder cancer: a meta-analysis of the published results of randomized clinical trials. J Urol. 2002 Nov;168(5):1964-70. link to original article PubMed
  5. CUETO study 95011: Ojea A, Nogueira JL, Solsona E, Flores N, Gómez JM, Molina JR, Chantada V, Camacho JE, Piñeiro LM, Rodríguez RH, Isorna S, Blas M, Martínez-Piñeiro JA, Madero R; CUETO Group (Club Urológico Español De Tratamiento Oncológico). A multicentre, randomised prospective trial comparing three intravesical adjuvant therapies for intermediate-risk superficial bladder cancer: low-dose bacillus Calmette-Guérin (27 mg) versus very low-dose bacillus Calmette-Guérin (13.5 mg) versus mitomycin C. Eur Urol. 2007 Nov;52(5):1398-406. Epub 2007 Apr 27. link to original article contains verified protocol PubMed

Regimen in use at