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Drug therapy of bladder cancer

Drug therapy for treatment of transitional epithelial cancer can be given either intravesically via rinsing (BCG/chemotherapy) or as systemic treatment with chemotherapy.

Supplementary treatment of superficial bladder cancer T1

In the last 20 years, immunological treatment with BCG has been the dominating intravesical instillation treatment. Intravesicle instillation of chemotherapy aimed at reducing the chance of recurrence has also been used to treat urothelial cancer of the bladder for many years. Today, flushing is mainly performed as part of adjuvant treatment in combination with a transurethral resection (TUR-B) as a single treatment at the end of the surgery.

Intravesical instillation treatment 

Intravesical instillation of immune-modulating substances, such as BCG or cytotoxic drugs, are used to treat carcinoma in situ (Tis), or to prevent new recurrence after resection of recurring superficial tumors (≤ T1) with or without accompanying Tis.  

A single instillation of a cytotoxic drug immediately after a TUR-B is used for all papillary superficial tumors.

A single instillation with epirubicin (80 mg) or mitomycin C (40 mg) within 6 hours after TUR-B reduces the frequency of recurrence by about 50% in a two year period, and is recommended for all superficial tumors, except if the bladder is perforated or there is postoperative bleeding requiring treatment. The medication is instilled and the catheter is closed for 1-2 hours (anticholinergic drug for bladder tenesmus) and opened thereafter.

The instillation regimen for high risk tumors consists of an induction cycle (usually 6 weekly instillations) and a maintenance cycle (different schedules over 1-3 years) with BCG or chemotherapy. 

Chemotherapy is considered for:

  • Recurring tumors of grade 1-2
  • Intolerable side effects from BCG 
  • No response to BCG with Ta tumors ("cross over")
  • Contraindications for BCG

In some patients, especially elderly, chemotherapy should be considered because of better tolerability than BCG, when there is no obvious need for the long-term effect of BCG.

Systemic treatment of localized muscle-infiltrating bladder cancer T2-T4a, cN0M0

As radical treatment, systemic chemotherapy has been attempted as neoadjuvant or adjuvant treatment. Multiple randomized studies have shown that neoadjuvant chemotherapy improves survival for muscle-infiltrating bladder cancer (1,2). All patients with muscle-infiltrating bladder cancer should therefore be assessed by a multidisciplinary team to optimize treatment. Normally, three cycles of cisplatin and gemcitabin are given and evaluated after two cycles.  In certain patients, HD-MVAC is indicated. However, the general condition of the patient and kidney status must be taken into consideration. Neoadjuvant chemotherapy is not recommended if ECOG function status is 2 and/or significantly reduced kidney function.

For locally advanced disease, chemotherapy can be given as induction therapy to render inoperable tumors operable. After a radical operation with spreading to regional lymph nodes, adjuvant therapy may be considered, preferably within the framework of a clinical study.

Systemic treatment for metastatic disease

Systemic chemotherapy for urothelial cancer has not provided the results hoped for, but there is a clear indication to consider chemotherapy for metastatic disease, in addition to experimental multimodal treatment with surgery, chemotherapy, and radiation.

Tumors of transitional epithelium are moderately sensitive to chemotherapy drugs such as cisplatin (Platinol®), methotrexate (Emthexat®/Metoject®), vinblastin (Velbe®), doxorubicin (Adriamycin®/Caelyx®), gemcitabine (Gemzar®), and paclitaxel (Taxol®). Vinflunine (Javlor®) is used as second-line treatment. Using a combination of these drugs, an objective response rate of 60-70% can be obtained. The most commonly used combination at Oslo University Hospital today is cisplatin and gemcitabine.

Side effects

The side effects are bone marrow inhibition with the danger of febrile leukopenia, as well as nausea and hair loss. Cisplatin is oto/nephrotoxic. In patients with heart and kidney failure, cisplatin is often contraindicated due to kidney toxicity and fluid accumulation during cycles. For reduced kidney function, replacing cisplatin with carboplatin may be considered. 

Chemotherapy drugs

Some of the drugs given for chemotherapy can be found in the National Registry for Chemotherapy Drugs. 

 

 

 

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