A phase 2 study of TMX-101, intravesical imiquimod,for the treatment of carcinoma in situ bladder cancer

Purpose

Imiquimod is a toll-like receptor agonist with proven antitumor activity as a topical treatment for skin cancer. TMX-101 (Vesimune) is a novel liquid formulation of imiquimod optimized for intravesical delivery. The agent demonstrated safety as an intravesical treatment for non–muscle-invasive bladder cancer in a phase 1 clinical trial. We report the results of a phase 2 prospective multicenter clinical trial assessing the safety and activity of TMX-101.

Desflurane and isoflurane in surgical patients: comparison of emergence time

In order to examine the clinical potential of desflurane (difluoromethyl-1-fluoro-2,2,2-trifluoroethyl ether) in humans, a randomized, controlled study was designed to compare time of emergence from anesthesia in patients undergoing elective surgery under desflurane anesthesia to that of patients under isoflurane anesthesia. Twenty-eight patients were randomly divided into four groups. Group 1 received isoflurane 0.65 MAC; group 2, desflurane 0.65 MAC; group 3, isoflurane 1.25 MAC; and group 4, desflurane 1.25 MAC. Anesthesia was induced with sodium thiopental, and N2O 60% was added to the volatile agent. Mean anesthetic exposure times (min [mean +/- SD]) were 108 +/- 49 in group 1, 132 +/- 46 in group 2, 147 +/- 74 in group 3, and 166 +/- 71 in group 4, with no significant differences between groups. The times from discontinuation of anesthetic gases until patients opened their eyes and squeezed the investigator's hand in response to a command were averaged and recorded as "emergence time." Emergence time was significantly less with desflurane than with isoflurane given at the same MAC. Patients receiving isoflurane 0.65 MAC responded to commands 15.6 +/- 4.3 min after discontinuation of the anesthetic; patients in the desflurane 0.65 MAC group responded in 8.8 +/- 2.7 min (P less than 0.01). Emergence time for isoflurane 1.25 MAC was 30.0 +/- 11.0 min; for desflurane 1.25 MAC it was 16.1 +/- 6.0 min (P less than 0.05). Our results confirm that emergence from desflurane anesthesia is more rapid than from isoflurane.     

Neoadjuvant targeted therapy and advanced kidney cancer: observations and implications for a new treatment paradigm

OBJECTIVE

To evaluate our early experience with neoadjuvant therapy (sunitinib or sorafenib) in advanced renal cell carcinoma (RCC), to explore the effect on both tumour biology and potential for downstaging advanced tumours, as systemic therapy for RCC has historically resulted in little if any primary tumour response, but recent experience with targeted therapy suggests otherwise.

PATIENTS AND METHODS

The preliminary experience with neoadjuvant therapy for the surgical management of RCC was reviewed at two large referral centres. Several unique patients were identified who had a novel response to systemic therapy that altered the surgical strategy.

RESULTS

Four patients who had targeted therapy before surgery are described and in whom there were effects on tumour biology not seen previously with chemotherapy and cytokine therapy. The selected patients who had neoadjuvant targeted therapy had shrinkage of a tumour thrombus in the inferior vena cava, nodal involvement, renal fossa recurrence and tumour within a solitary kidney.

CONCLUSIONS

The introduction of new molecular agents has revolutionized the treatment of patients with metastatic RCC. Responses to targeted therapy within the primary tumour, tumour thrombus, renal fossa recurrence, and lymph node metastases are novel findings not seen during treatment with immunotherapeutic‐based strategies. This might be a signal for urological surgeons to re‐evaluate the paradigm for the surgical management of advanced RCC. Potential applications are presented to encourage further investigations with targeted therapy in the neoadjuvant setting.     

Ureteral tumor thrombus from renal cell carcinoma extending into bladder

Tumor thrombus from renal cell carcinoma (RCC) usually occurs within the renal vein. We present the first report of a tumor thrombus from RCC extending from the kidney down the ureter and into the lumen of the bladder. This case both: (1) provides evidence for growth of RCC along the urinary tract, and (2) poses a staging dilemma.     

Surveillance for renal cell carcinoma: why and how? When and how often?

Patient's history, physical examination, laboratory tests, and radiographic evaluation are the cornerstones of postoperative surveillance. It has been shown that localized renal cell carcinoma (RCC) can recur in nearly all organs of the body, but most commonly in the lung, bone, liver, brain, and renal fossa. Lung metastases can be sensitively detected through radiographic evaluation. Treatment of lung metastases might prolong survival, which supports surveillance x-ray or computed tomography scans. Surgical treatment of early detected liver metastases and local recurrences may also prolong survival, which supports a close abdominal surveillance program. Brain and bone metastases are usually symptomatic when they occur, and their treatment is generally palliative. Hence, surveillance protocols do not usually include their routine radiographic evaluation. Because partial nephrectomy does not increase the risk of local recurrence over radical nephrectomy, we recommend identical surveillance for completely resected tumors regardless of surgical approach. The risk of recurrence after nephrectomy is generally related to tumor stage, tumor grade, and patient performance status. The majority of recurrences occur within the first 5 years after surgery, supporting a more intense surveillance strategy within the first 5 years. The University of California Integrated Staging System (UISS) combines TNM stage, Fuhrman grade, and performance status, and categorizes patients into 3 different risk groups. The current surveillance protocol at our institution is based on the UISS. It is expected that molecular markers such as p53 will allow more individualized surveillance strategies in the future.     

Combined cytoreductive laser therapy and immunotherapy for palliation of metastatic renal cell carcinoma to the head and neck

Interleukin-2 (IL-2) remains the mainstay of treatment for metastatic renal cell carcinoma (RCC), but minimally invasive surgical techniques have provided new options for the combined treatment of RCC. Two patients with metastatic RCC to the head and neck treated by combined laser-induced thermal therapy and IL-2 were described in this case report. Both patients had an extended survival compared to the historical survival of 10 months for metastatic RCC but eventually succumbed to progressive disease. The authors’ initial experience with metastatic RCC suggests that laser thermoablation and immunotherapy in selected patients with metastatic RCC is warranted as a palliative treatment, but a larger study with long-term follow-up is necessary to determine the effectiveness of this approach.