Peg Esper

MEASURING QUALITY OF LIFE IN MEN WITH PROSTATE CANCER USING THE FUNCTIONAL ASSESSMENT OF CANCER THERAPY-PROSTATE INSTRUMENT

OBJECTIVES As the incidence of prostate cancer in the United States exceeds 330,000 in 1997, increasingly more men are faced with treatment choices for which there is no clear approach. At every stage of disease, these treatment choices may involve clinically equivalent modalities that differ in side effects and impact upon quality of life (QOL). Comprehensive, yet efficient, questionnaires are needed to measure QOL in patients with prostate cancer. METHODS Developed as a disease-specific adjunct to the Functional Assessment of Cancer Therapy (FACT) measurement system, a 12-item prostate cancer subscale (PCS) was developed and tested in three independent samples: a subscale development sample (n = 43), validity sample 1 (n = 34), and validity sample 2 (n = 96). The 12 items ask about symptoms and problems specific to prostate cancer. These questions are added to the general (FACT-G) instrument, thereby comprising a 47-item questionnaire. RESULTS Internal consistency of the PCS ranged from 0.65 to 0.69, with coefficients for FACT-G subscales and aggregated scores ranging from 0.61 to 0.90. Concurrent validity was confirmed by the ability to discriminate patients by disease stage, performance status, and baseline prostate-specific antigen (PSA) level. Sensitivity to change in performance status and PSA score over a 2-month period suggested that some subscales of the FACT-Prostate (P) (including the PCS) are sensitive to meaningful clinical change. CONCLUSIONS Our findings support use of the FACT-P as a meaningful component of QOL evaluation in men undergoing therapy for prostate cancer.

Psychiatric Side Effects of Interferon Therapy: Prevalence, Proposed Mechanisms, and Future Directions

The increasing use of interferon (IFN) in treating a variety of disorders including, malignant melanoma and hepatitis C, has resulted in the identification and increasing concern about the psychiatric side effects that can result from treatment. These effects can occur either shortly after beginning IFN therapy or later as a result of continued treatment. Studies have reported the incidence of later side effects, which include symptoms of depression, anxiety, and occasional suicidal ideation, to be from 0% to 70%. Case studies have demonstrated that pharmacologic interventions are beneficial in reducing iatrogenic psychiatric symptoms while allowing patients to maintain IFN therapy. The present article provides an overview of the psychiatric effects of IFN therapy, the proposed mechanisms of these side effects, and case studies that provide mechanistic support. In addition, limitations of the current literature are provided with suggestions for treating physicians and a discussion of possible future research directions.

Phase II Trial of Oral Estramustine, Oral Etoposide, and Intravenous Paclitaxel in Hormone-Refractory Prostate Cancer

PURPOSE To evaluate the combination of intravenous (IV) paclitaxel, oral estramustine, and oral etoposide in patients with advanced hormone-refractory prostate cancer. PATIENTS AND METHODS Forty patients with carcinoma of the prostate that was progressing despite hormonal therapy and who had undergone antiandrogen withdrawal (if previously treated with an antiandrogen) were enrolled onto this phase II trial. Patients were treated with oral estramustine 280 mg tid and oral etoposide 100 mg/d for 7 days, with paclitaxel 135 mg/m(2) IV over 1 hour on day 2 of each 21-day treatment cycle. Patients received a maximum of six cycles of therapy. RESULTS Thirty-seven patients were assessable for response. Twenty-two had measurable disease at baseline; response was not assessable in six of these patients. Overall response was 45% (10 of 22 patients; 95% confidence interval [CI], 24% to 68%), and response was 63% (10 of 16) in assessable patients. Twenty-six patients had a > or = 50% decrease from their baseline prostate-specific antigen levels during therapy, for a response rate of 65% (95% CI, 48% to 79%) by this criterion. Median duration of response was 3.2 months, with an estimated median survival of 12.8 months. Major toxicities of therapy were leukopenia (eight patients had > or = grade 4 leukopenia) and anemia. Hematologic toxicity seemed to be associated with liver metastases. Serial measurements in 24 patients using the Functional Assessment of Cancer Therapy-Prostate (FACT-P) showed no significant change in quality of life (QOL) as a result of therapy. CONCLUSION The combination of IV paclitaxel, oral estramustine, and oral etoposide is active in patients with advanced prostate cancer. The regimen is tolerable and does not have a significant impact on QOL as measured by the FACT-P in a limited sample of patients.

Combined-Modality Therapy With Gemcitabine and Radiotherapy As a Bladder Preservation Strategy: Results of a Phase I Trial

PURPOSE We conducted a phase I trial of gemcitabine given twice weekly with concurrent radiotherapy in patients with muscle-invasive bladder cancer. PATIENTS AND METHODS Eligible patients underwent maximal transurethral resection of their bladder tumors followed by twice-weekly infusion of gemcitabine with 2 Gy/d concurrent radiotherapy to the bladder, for a total of 60 Gy over 6 weeks. The starting dose of gemcitabine was 10 mg/m(2) with subsequent dose levels of 20, 27, 30, and 33 mg/m(2). The primary end point was the determination of the maximum-tolerated dose (MTD) of twice weekly gemcitabine with concurrent radiotherapy. Secondary end points included assessment of toxicity associated with combined-modality therapy and initial assessment of the rate of bladder preservation. RESULTS Twenty-four patients were enrolled and 23 were assessable for toxicity and response. No significant toxicity was demonstrated at the 10 or 20 mg/m(2) twice-weekly doses. Dose-limiting toxicity (DLT) occurred in two of three patients treated at 33 mg/m(2). Intermediate dose levels of 27 and 30 mg/m(2) were then evaluated. The MTD of gemcitabine was 27 mg/m(2). The DLT was systemic, manifested as an elevation in liver function tests, malaise, and edema. Fifteen of 23 patients (65%) are alive with bladders intact and no evidence of recurrent disease at a median follow-up of 43 months. CONCLUSION Twice-weekly gemcitabine with concurrent radiotherapy at 2 Gy/d to a total dose of 60 Gy is well-tolerated. The MTD of gemcitabine is 27 mg/m(2). There is a high rate of bladder preservation in this selected group of patients.

Phase Ib trial assessing autologous, tumor-pulsed dendritic cells as a vaccine administered with or without IL-2 in patients with metastatic melanoma

Twenty-four subjects with metastatic melanoma were treated on a randomized Phase Ib trial evaluating an autologous tumor lysate-pulsed dendritic cell (DC) vaccine with or without interleukin (IL)-2. The vaccine consisted of autologous DCs obtained from peripheral blood mononuclear cells (PBMCs) cultured in granulocyte macrophage-colony stimulating factor and IL-4 then pulsed with autologous tumor cell lysate and keyhole limpet hemocyanin (KLH). The primary end points of the trial were safety and immune response to vaccine. Subjects were randomized to vaccine administered every other week times 3, vaccine×3 followed by low-dose IL-2, or vaccine×3 followed by high-dose IL-2. Immune response was monitored pretreatment and at 2 and 4 weeks after the third vaccine administration. Disease evaluation was performed at 4 weeks after the third vaccination. Therapy was well tolerated with no local vaccine toxicity greater than grade 1 in any arm. IL-2 toxicity was as expected without additional toxicity from the addition of IL-2 to vaccine. Immune response defined as delayed-type hypersensitivity, PBMC interferon-γ enzyme-linked immunosorbent spot, and PBMC proliferation, to both autologous tumor and KLH were detected in all arms. Interferon-γ enzyme-linked immunosorbent spot response to KLH (7 of 10 patients) and autologous tumor (4 of 10 patients) were also detected in subjects with available vaccine draining lymph node cells. There were no differences in immune response between treatment arms. No clinical responses were seen. Autologous tumor lysate-pulsed DC vaccine with or without IL-2 was well tolerated and immunogenic but failed to induce clinical response in patients with advanced melanoma.

Placental metastasis of maternal melanoma.

Metastasis of maternal malignant tumor to the products of conception is a rare event. Melanoma is the most common maternal malignant tumor to metastasize to the placenta and the fetus. We report the case of a 28-year-old woman with melanoma during pregnancy. At parturition, histologic evaluation of the placenta revealed metastatic melanoma, and multiple organ metastasis developed. The infant was free of disease. Metastasis to products of conception portends a poor prognosis for the mother. To our knowledge, this report is the first of a patient with melanoma metastasis to the placenta to survive more than 7 months after parturition. As caretakers of patients with melanoma, dermatologists are in a position to coordinate and direct the care and follow-up treatment of affected patients.

SUPPORTIVE CARE, PAIN MANAGEMENT, AND QUALITY OF LIFE IN ADVANCED PROSTATE CANCER

Despite achievements in the area of providing care for patients with advanced prostate cancer, ample work remains. Additional research is needed regarding the control of pain from bone metastases and the management of fatigue and urinary symptoms. Investigators have only begun to explore the area of quality of life research in patients with prostate cancer. Other issues not addressed in this article that are significant to the care of these patients include caregiver burden and end-of-life care. These areas significantly affect quality of life. The supportive care, pain management, and quality of life issues discussed herein present many challenges to health care providers. Close attention to what patients tell us about their care will make the challenge more attainable and the caregiving more satisfying.

Phase II trial of paclitaxel, estramustine, etoposide, and carboplatin in the treatment of patients with hormone-refractory prostate carcinoma

Preclinical data suggest that the combination of intravenous (i.v.) paclitaxel, carboplatin, oral etoposide, and oral estramustine (TEEC) has significant activity in patients with advanced, hormone‐refractory prostate carcinoma. The authors conducted this clinical trial to evaluate the addition of carboplatin to the three‐drug combination of paclitaxel, estramustine, and etoposide (TEE).

Phase II trial of oral cyclophosphamide, prednisone, and diethylstilbestrol for androgen-independent prostate carcinoma

The authors evaluated the combination of oral cyclophosphamide, oral prednisone, and diethylstilbestrol (DES) in patients with androgen‐independent prostate carcinoma (AIPC).

A new concept in cancer care: the supportive care program.

This article describes the findings of a pilot program designed to enter advanced prostate cancer patients into the hospice benefit while they are still being actively treated, but in situations where treatment is known to be primarily palliative in nature. The supportive care program (SCP) combines the medical model’s goal to prolong life with the goal of hospice to palliate symptoms and improve quality of life (QOL). The concept of a SCP was developed to create a team approach where advanced prostate cancer patients who are starting investigational chemotherapy are concurrently enrolled into a hospice program. The objectives were to identify whether SCP improved QOL and continuity of care while remaining cost-effective. Data were collected on patient quality of life, performance status, use of health care resources, and costs for the 36 enrolled patients. A comparison was made to a matched set of 23 control patients. Our findings indicate that the SCP contributes to continuity of care while being cost-effective.