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Bladder

What is the first-line systemic treatment for metastatic transitional cell bladder cancer?

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Key concept

Cisplatin-based combination chemotherapy is the backbone treatment for metastatic urothelial carcinoma. In patients who are not candidates for cisplatin-based therapy, other options include carboplatin-based regimens, non–platinum-based regimens, and immunotherapy.

Clinical scenario

A 45-year-old woman with a history of bladder cancer treated with neoadjuvant chemotherapy and radical cystectomy presents with weight loss and back pain. CT scan of chest, abdomen, and pelvis reveal diffuse bony lesions for which the biopsy is positive for urothelial carcinoma. The patient has no other medical problems and has good performance status (PS). How should this patient be treated?

Action items

Systemic treatment depends on whether the patient is deemed fit for cisplatin-based chemotherapy. Patients who have any of the following are deemed at higher risk of complications from cisplatin: ECOG PS ≥2, estimated glomerular filtration rate <60 mL/min, hearing loss, grade ≥2 peripheral neuropathy, NY Heart Association congestive heart failure score ≥3. For patients with impaired renal function, it is important to correct any reversible etiologies (such as obstruction) before deeming a patient not a candidate for cisplatin.1,2

For patients who are candidates for cisplatin-based combination chemotherapy:

  • Methotrexate/vinblastine/doxorubicin/cisplatin (MVAC), dose-dense administration preferred

  • Gemcitabine/cisplatin (GC)

  • Paclitaxel/gemcitabine/cisplatin (PGC)

For patients who are not candidates for cisplatin-based combination chemotherapy:

  • Carboplatin-based regimen (ie, carboplatin and gemcitabine)

  • Non–platinum-based regimen (ie, paclitaxel and gemcitabine)

  • PD1/PD-L1 inhibitors (both atezolizumab and pembrolizumab are FDA-approved in this setting)

Discussion

In a randomized multicenter trial, the MVAC regimen proved superior to single-agent cisplatin in term of overall response rate (ORR), progression-free survival (PFS), and overall survival (OS) at the expense of increased toxicity.3 In another clinical trial, dose-dense (every 2 weeks) administration of MVAC with growth factor support was shown to be associated with greater PFS and complete response, trend toward improved OS, and less myelotoxicity.4 Another large international study revealed that the GC regimen resulted in equal clinical efficacy compared to standard MVAC but with less serious toxicity in patients with metastatic urothelial carcinoma.5 In the EORTC30987 trial, the addition of paclitaxel to the GC regimen yielded a higher response rate and a non-significant improvement in OS, at the expense of increased rates of grade 3/4 toxicities.6

Although carboplatin-based regimens have not been compared head to head with cisplatin-based regimens, they have proven efficacy in patients unable to receive cisplatin. For example, in the EORTC30896 trial, carboplatin/gemcitabine was equal to methotrexate/carboplatin/vinblastine with fewer adverse effects.7 The data supporting the use of PD1/PD-L1 inhibitors is discussed in another question.

References
  1. Up-to-date. Available at: https://www.uptodate.com.

  2. NCCN guidelines for bladder cancer. Available at: https://www.nccn.org.

  3. Loehrer PJ Sr, Einhorn LH, Elson PJ, et al. A randomized comparison of cisplatin alone or in combination with methotrexate, vinblastine, and doxorubicin in patients with metastatic urothelial carcinoma: a cooperative group study. J Clin Oncol 1992;10(7):1066-73.

  4. Sternberg CN, de Mulder P, Schornagel JH, et al. Seven year update of an EORTC phase III trial of high-dose intensity M-VAC chemotherapy and G-CSF versus classic M-VAC in advanced urothelial tract tumours. Eur J Cancer 2006;42(1):50-4.

  5. Von der Maase H, Hansen SW, ...

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