Interleukin-2 improves tumour response to DNP-modified autologous vaccine for the treatment of metastatic malignant melanoma.

This paper is a report of response rate (RR) and survival of 34 metastatic melanoma patients who received a dinitrophenyl (DNP)-modified autologous melanoma cell vaccine. In all, 27 patients started the vaccine as a primary treatment for metastatic melanoma and seven started it as an adjuvant, with no evidence of disease at the time, but had developed new metastases. Interleukin-2 (IL-2) was administered in 24 out of the 34 patients: 19 who progressed on vaccine alone and five who had the combination from start. Interleukin-2 was administered in the intravenous, bolus high-dose regimen (seven patients) or as subcutaneous (s.c.) low-dose treatment (17). Overall response for the entire group was 35% (12 patients out of 34), 12% having a complete response (CR) and 23% a partial response (PR). However, only two patients had tumour responses while on the vaccine alone, whereas the other 10 demonstrated objective tumour regression following the combination with IL-2 (two CR, eight PR), lasting for a median duration of 6 months (range 3-50 months). Of the 12 responding patients, 11 attained strong skin reactivity to the s.c. injection of irradiated, unmodified autologous melanoma cells. None of the patients with a negative reactivity experienced any tumour response. Patients with positive skin reactions survived longer (median survival - 54 months). The results suggest enhanced RRs to the combination of IL-2 and autologous melanoma vaccine. Skin reactivity to unmodified autologous melanoma cells may be a predictor of response and improved survival, and therefore a criterion for further pursuing of immunotherapeutic strategies.

Determinants of the use of complementary therapies by patients with cancer.

PURPOSE: We performed a survey of Israeli oncology patients to examine the extent of their use of complementary therapies (CT) and to compare sociodemographic, psychologic, and medical characteristics, attitudes, and quality of life of users and nonusers of CT. PATIENTS AND METHODS: Questionnaires were administered to 1,027 patients attending ambulatory and inpatient hematology or oncology facilities at three hospitals. Medical information was extracted from charts. Univariate and multivariate comparisons of users and nonusers of CT were performed. RESULTS: A total of 526 participants (51.2%) had used CT since their diagnosis, and 357 patients (34.9%) had used CT recently (in the past 3 months). Factors that multivariate analysis found to be significantly associated (P <.05) with recent CT use were as follows: female sex; age 35 to 59 years; more education; coming to the hospital by private car; advanced disease status; having a close friend or a relative with cancer; and attending support groups or individual counseling. After controlling for these factors, individually examined psychosocial variables associated with recent CT use included the following (odds ratios [OR] with 95% confidence intervals [CI]): needs unmet by conventional medicine (OR, 2.76; 95% CI, 1.95 to 3.89); helplessness (OR, 1.39; 95% CI, 1.0 to 1.91); incomplete trust in the doctor (OR, 1.49; 95% CI, 1.08 to 2.06); and changed outlook or beliefs since the diagnosis of cancer (OR, 1.47; 95% CI, 1.07 to 2.02). Functional quality of life (including physical, emotional, social, and role function) and symptom (fatigue and diarrhea) scores were significantly worse for recent CT users compared with nonusers, controlling for age, sex, and current disease status. CONCLUSION: Characteristics associated with CT use include age, sex, education, and advanced disease. Significant associations between CT use and attending supportive psychotherapy, unmet needs, helplessness, and worse emotional and social function indicate considerable distress, suggesting that increased attention to psychosocial needs within oncologic settings is warranted.

Genetic testing of breast and ovarian cancer patients: clinical characteristics and hormonal risk modifiers.

OBJECTIVES: Carriers of the mutations 185delAG and 5382insC in the BRCA1 gene and 6174delT in the BRCA2 gene have a substantial life-time risk for breast and ovarian cancers (BC and OC). The aim of the study was to identify the clinical features and the hormonal risk modifiers in mutation carriers and the implication in suggested guidelines for treatment decisions in BRCA1/2 carrier patients. STUDY DESIGN: Breast and/or ovarian cancer patients from the Oncology and Cancer Genetic clinics were tested for the three Ashkenazi founder mutations: 87 patients were identified as carriers of one of these mutations. Clinical presentation and age at onset were correlated with the mutations, in patients with bilateral BC or BC and OC, the length of time that elapsed between the diagnosis of the two cancers was recorded. We compared BC and OC patients with regard to ages at menarche, first pregnancy and menopause, number of pregnancies and deliveries, the use of oral contraceptives, hormonal replacement therapy and fertility treatments. RESULTS: The carriers of the three BRCA1/2 Ashkenazi founder mutations did not differ in clinical presentation nor age at onset. Forty-three patients (74.1%) of 58 BC patients were diagnosed between the ages 30 and 50, only four (6.9%) patients were diagnosed after age 60. Of BC patients diagnosed before age 35, 63.6% developed second BC as compared to 25.5% of those diagnosed after age 35. Ovarian cancer was diagnosed after age 45 in 89.7% of the patients, only one patient was diagnosed under the age of 40. Oral contraceptives use was documented in 61.3% of BC patients as compared to 11.8% of OC patients. Other hormonal factors did not differ between the two groups. CONCLUSIONS: The carriers of the three Ashkenazi founder mutations should be considered at the same risk for BC and for OC and treatment options should be the same. Mutation carriers diagnosed with BC before the age of 35 are at a very high risk for developing second breast cancer. Most ovarian cancers in carriers were diagnosed after age 45, and prophylactic oophorectomy should be postponed to the age of 45. Oral contraceptives might elevate the risk of BC in mutation carriers.

The Effect of Genetic Counseling on Knowledge and Perceptions Regarding Risks for Breast Cancer.

In 1994, a clinic for cancer risk counseling was opened at Hadassah University Hospital in Jerusalem. Most of the counselees have been women who had breast cancer and/or a relative with breast cancer. In order to evaluate the effect of this counseling on women's knowledge and perceptions regarding the risks for breast cancer, a questionnaire was given before and after the counseling session to 60 healthy women who came to the clinic because they have relatives with breast cancer. According to the genetic counselors' estimations, most of these women had a significantly increased risk (compared to the general population) of developing cancer. Before counseling, the women overestimated the population risk for breast cancer, the contribution of heredity to morbidity of cancer, and their own risks to get cancer. After counseling session, they gave reduced estimates, closer to the "real" ones. The subjective perceptions regarding these risks were reduced after counseling, except for the perceptions regarding their relativerisks which have not changed after the counseling. About 90% of the women who came to the clinic wanted to be tested for genetic predisposition to cancer. For most of these women, the expectations that the test can rule out a genetic predisposition to cancer became more realistic after the counseling. The option to first test an affected relative was offered to all families, and a test was actually conducted in 75% of the families.

The founder mutations 185delAG and 5382insC in BRCA1 and 6174delT in BRCA2 appear in 60% of ovarian cancer and 30% of early-onset breast cancer patients among Ashkenazi women.

The mutations 185delAG, 188del11, and 5382insC in the BRCA1 gene and 6174delT in the BRCA2 gene were analyzed in 199 Ashkenazi and 44 non-Ashkenazi Jewish unrelated patients with breast and/or ovarian cancer. Of the Jewish Ashkenazi women with ovarian cancer, 62% (13/21) had one of the target mutations, as did 30% (13/43) of women with breast cancer alone diagnosed before the age 40 years and 10% (15/141) of those with breast cancer diagnosed after the age 40 years. Age at ovarian cancer diagnosis was not associated with carrier status. Of 99 Ashkenazi patients with no family history of breast and/or ovarian cancer, 10% carried one of the mutations; in two of them the mutation was proved to be paternally transmitted. One non-Ashkenazi Jewish ovarian cancer patient from Iraq carried the 185delAG mutation. Individual mutation frequencies among breast cancer Ashkenazi patients were 6.7% for 185delAG, 2.2% for 5382insC, and 4.5% for 6174delT, among ovarian cancer patients; 185delAG and 6174delT were about equally common (33% and 29%, respectively), but no ovarian cancer patient carried the 5382insC. More mutations responsible for inherited breast and ovarian cancer probably remain to be found in this population, since 79% of high-incidence breast cancer families and 35% of high-incidence breast/ovarian cancer families had none of the three known founder mutations.