In the USA, bladder cancer ranks 4th and 11th for cancer incidence in males and females, respectively. Whereas urothelial carcinoma (UC) accounts for 90 % of all bladder cancers, superficial UC, defined as non-muscle invasive cancer, represents 60 % of cases and requires local therapy with TURB (Trans-Urethral Resection of Bladder) and subsequent intravesical instillations [1, 2]. UC presents localized muscle invasion or distant metastases in 30 and 10 % of remaining cases, respectively. The management of muscle invasive disease includes neoadjuvant or adjuvant chemotherapy associated with cystectomy . Despite surgery, 5-years survival varies between 36 and 48 %. In fact, peri-operative chemotherapy produce a benefit of approximately 5–7 % and a consistent part of patients develops recurrence of disease. The treatment of patients with recurrent or metastatic disease is currently represented by chemotherapy. As first-line therapy, Cisplatin and Gemcitabine (CG) demonstrated a similar efficacy of MVAC (Metotrexate, Vinblastine, Doxorubicin, Cisplatin) schedule with a more favourable toxicity profile . Therefore, CG is the preferred option in first-line setting. However, considering that UC mainly develops in elderly patient (with a median age at diagnosis of approximately 70 years), the event of treating a patient un-fit for cisplatin is not unusual . Un-fit patients are defined by the presence of at least one of the following: Eastern Cooperative Oncology Group Performance Status (ECOG PS) = 2, clearance of creatinine < 60 mL/min, grade ≥ 2 hearing loss or peripheral neuropathy [according to National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE)], heart failure (New York Heart Association functional classification class III). In these cases, carboplatin instead of cisplatin may be an option .
So far, vinflunine (VFL) is the only drug approved after failure of platinum-based treatment in Europe. It has been registered on the basis of a phase III trial that compared VFL versus best supportive care in second line setting, demonstrating a benefit of 2.6 months in median overall survival (OS) . Principal VFL-related side effects include: constipation, anemia, neutropenia, vomiting and stomatitis. However, VFL has been proved to be acceptable also for elderly patients if dose reduction and granulocyte-colony stimulating factors (G-CSF) prophylaxis are observed . With this evidence, the activity of a VFL based doublet as first-line therapy has been successfully explored in a phase II trial conducted in patients un-fit for cisplatin and a phase III trial comparing VFL-gemcitabine versus carboplatin-gemcitabine in the same setting is ongoing . Even if preliminary data of check-point inhibition are encouraging also in UC patients, results from ongoing randomized trials will not be available before a couple of years [9, 10]. In conclusion, chemotherapy still play a crucial role in UC management and VFL is expected to be one of the protagonists in the next years scenario.
Smoking habit is the most important risk factor associated with the development of UC in west countries. Another well known risk factor is the exposition to aromatic amines and aniline derivatives . Recently, a higher incidence of UC has been documented in a large series of patients who received renal transplantation . Authors evidenced that patients diagnosed with bladder UC after renal transplantation were younger and presented more aggressive and advanced disease. The immune suppression required after transplantation is considered to support UC carcinogenesis process. Therefore, post-transplantation patients represent a particular subgroup of UC patients requiring special attention due to their comorbidity and concomitant immunosuppressive medications.
Here, we present a case report of a young kidney-transplanted patient who presented complete metabolic response after two cycles of second-line VFL chemotherapy. To our knowledge, this is the first report attesting the use of VFL in a patient under immunosuppressive therapy for kidney transplantation.