Results of the Southwest Oncology Group phase II evaluation (study S0031) of ZD1839 for advanced transitional cell carcinoma of the urothelium.

STUDY TYPE: Prognosis (inception cohort). LEVEL OF EVIDENCE: 1b. OBJECTIVE: To evaluate the epidermal growth factor receptor (EGFR)-targeted agent ZD1839 in patients who failed one previous chemotherapeutic regimen for metastatic transitional cell carcinoma (TCC), and to correlate patterns of response with the expression of EGFR. PATIENTS AND METHODS: Thirty-one patients with metastatic TCC of the urothelial tract were treated with ZD1839 500 mg oral daily. Patients were required to have a pretreatment biopsy to assess EGF expression. RESULTS: The median progression-free survival was 2 months, with only two patients (6.5%) surviving past 6 months with no disease progression. Thirty patients were evaluable for toxicity; there was grade 4 cerebrovascular ischaemia and an increase in creatinine level. All patients were evaluable for response, with one confirmed partial response (3%; 95% confidence interval, CI, 0-17%) in a patient with pulmonary metastases. All patients have died, and the estimated median (95% CI) survival is 3 (2-7) months. CONCLUSIONS: ZD1839 is ineffective as a second-line agent for urothelial carcinoma.

A phase ii study of gemcitabine and capecitabine in patients with advanced renal cell cancer: Southwest Oncology Group Study S0312.

OBJECTIVES: Gemcitabine plus capecitabine has moderate efficacy in patients with advanced renal cell cancer (RCC) but has considerable toxicity. We evaluated the efficacy and toxicity of a modified dose-schedule of this doublet in patients with metastatic RCC. METHODS: Chemotherapy-naive patients were treated with gemcitabine at 900 mg/m2 on days 1, 8, and 15 and with capecitabine at 625 mg/m2 twice daily on days 1 through 21, and every 28 days thereafter. The primary end point was response rate (RR). No further evaluation of this regimen would be pursued if the RR was ≤ 5%. In an exploratory analysis, we also evaluated potential markers of prognosis and treatment response, including thymidylate synthase, PTEN, pAKT, pmTOR, XRCC1, and ERCC1. RESULTS: Of 43 patients, 1 was ineligible and 2 were not analyzable. There was 1 complete response and 3 partial responses, for an overall RR of 10% (95% CI = 3, 24). Nineteen patients (48%) had stable disease. The 6-month freedom-from-treatment-failure and overall survival rates were 20% (95% CI = 8, 32) and 75% (95% CI = 62, 88), respectively. Median survival time was 23 months (95% CI = 10, 37). One patient each experienced grade 4 neutropenia, fatigue, thrombocytopenia, and hemolysis with renal failure. The most common grade 3 toxicities were neutropenia (12 patients), fatigue (5), and leucopenia (4). Patients with a best response of stable disease or better were more likely to have decreased expression of PTEN and increased expression of pmTOR. CONCLUSIONS: Gemcitabine plus capecitabine at this reduced dose-schedule benefits a small percentage of patients with RCC with an acceptable toxicity profile.

Evaluation of interferon alpha-2B and thalidomide in patients with disseminated malignant melanoma, phase 2, SWOG 0026.

BACKGROUND: Southwest Oncology Group protocol 0026 evaluated interferon alpha-2b plus thalidomide in patients with disseminated melanoma. Endpoints were 6-month progression-free survival rate, response rate, and toxicity. METHODS: Twenty-six patients with Stage IV melanoma, measurable or nonmeasurable disease, performance status of 0-2, and adequate renal and hepatic functions were registered. One prior systemic therapy for Stage IV disease was required. Interferon was administered subcutaneously (1 million U) twice daily; thalidomide was orally administered (200-400 mg) each evening in a dose-escalating manner. Response evaluations using Response Evaluation Criteria in Solid Tumors were performed every 8 weeks. RESULTS: After 2 sudden deaths and 1 grade 4 treatment-related pulmonary embolism, this study was temporarily closed. One patient with deep-vein thrombosis and 2 with grade 3 cardiac arrhythmias were reported. The relationship of these events to the treatment was worrisome but not definitive. Grade 3 treatment-related adverse events occurred in 14 of 26 patients. Because of concern for patient safety the study was permanently closed. No treatment responses were seen in the 22 evaluable patients. Estimated 6-month progression-free survival rate was 15% (95% confidence interval [CI], 2%-29%), estimated 6-month overall survival was 58% (95% CI, 39%-77%), and estimated response probability was 0 of 22 (95% CI, 0%-15%). CONCLUSIONS: This regimen demonstrated a lack of response and was associated with multiple severe toxicities. Further investigation of interferon alpha-2b and thalidomide in this dose and schedule is not warranted.

Squamous cell carcinoma of the scrotum in a radiation technologist and the use of sentinel lymph node biopsy in recurrent disease.

Squamous cell carcinoma (SCC) of the scrotum is an uncommon neoplasm. It has been described in many different occupations and is associated with a myriad of carcinogens, yet the etiology still remains a mystery. This is the first report of its occurrence in a radiation technologist. Additionally, the use of sentinel lymph node biopsy in SCC has been advocated as a safe method of limiting the morbidity associated with bilateral ilioinguinal dissections. This is the first report of its use in recurrent metastatic SCC of the scrotum.

Docetaxel-associated epiphora.

Docetaxel is a semisynthetic taxane indicated for the treatment of advanced breast, prostate, and non-small cell lung cancers; it is also used for the treatment of various other solid tumors. The standard intermittent dosage of docetaxel is 60-100 mg/m2 every 3 weeks. At this dose and schedule, myelosuppression is common and neutropenia is usually the dose-limiting toxicity. Weekly administration of docetaxel 20-42 mg/m2 is being tested in the treatment of advanced solid tumors in order to improve patient tolerance by reducing the interval dose and to maintain therapeutic efficacy by increasing overall dose intensity. Asthenia and peripheral neuropathy can limit continued administration of weekly docetaxel. Epiphora (excess tearing due to narrowing or blockage of the lacrimal outflow passages) is associated with repeated weekly administration of docetaxel. This adverse effect can interfere with activities of daily life and negatively affect quality of life. Epiphora may be an underreported adverse effect of treatment because of underrecognition by clinicians and patient embarrassment with respect to seemingly uncontrolled tearing. The use of weekly docetaxel administration is expanding; therefore, patients should be educated to recognize and report signs and symptoms of epiphora. It is important for clinicians participating in the care of patients undergoing treatment with docetaxel to monitor for excess tearing and signs of eye irritation to ensure timely management of treatment-related epiphora.