Etoposide, dexamethasone, cytarabine, and cisplatin in vincristine, doxorubicin, and dexamethasone-refractory myeloma

Based on remarkable activity in refractory lymphomas, a combination of etoposide, cisplatin (both administered by 4-day continuous infusions), cytarabine (Ara-C), and dexamethasone (EDAP) was evaluated in 20 patients with advanced myeloma refractory to standard melphalan and prednisone (MP) and/or vincristine, Adriamycin (doxorubicin; Adria Laboratories, Columbus, OH), and dexamethasone (VAD) and even to high doses of melphalan (HDM) (seven patients). Forty percent of patients responded regardless of previously recognized risk factors (eg, duration of drug resistance, tumor mass, and serum lactic dehydrogenase [LDH] level). While the median survival was only 4.5 months, patients with good performance (Zubrod less than 2) and low or intermediate tumor stage survived more than 14 months compared with only 2 months for the remaining group. EDAP could be readily administered in the outpatient clinic, but neutropenic fever prompted hospital admission in 80% of patients, half of whom developed penumonia and sepsis, a fatal outcome in four patients. Severe myelosuppression was of short duration, so that subsequent cycles could be administered every 3 to 4 weeks. No serious extramedullary toxicity, including renal toxicity, was encountered. Marrow toxicity and hence infectious complications may be reduced by elimination of Ara-C without compromising treatment efficacy. We conclude that the lack of cross-resistance with VAD and even HDM makes EDAP or a similar combination an attractive regiment to be formally explored in an alternating sequence with VAD in high-risk myeloma.     

Premenopausal intakes of vitamins A, C, and E, folate, and carotenoids, and risk of breast cancer.

Intakes of vitamins A, C, and E, folate, and carotenoids have been hypothesized to reduce the risk of breast cancer. However, previous epidemiological studies on these nutrients and breast cancer risk have been inconclusive, and have included primarily postmenopausal women. We examined the intake of these nutrients in relation to breast cancer risk among 90,655 premenopausal women ages 26-46 years in 1991 in the Nurses' Health Study II. Nutrient intake was assessed with a validated food-frequency questionnaire at baseline in 1991 and in 1995. During 8 years of follow-up from 1991 to 1999, we documented 714 incident cases of invasive breast cancer. Overall, none of the vitamins and carotenoids was strongly related to a reduced risk of breast cancer. However, intake of vitamin A, including preformed vitamin A and carotenoids, was associated with a reduced risk of breast cancer among smokers; participants in the highest quintile of total vitamin A intake had a multivariate relative risk of 0.28 (95% confidence interval 0.12-0.62; P, test for trend <0.001; P, test for interaction <0.001) compared with those in the lowest quintile of intake. We found no evidence that higher intakes of vitamins C and E, and folate in early adult life reduce risk of breast cancer. However, intake of vitamin A may be related to a reduced risk of breast cancer among smokers.     

Myelodysplastic syndromes, aging, and age: correlations, common mechanisms, and clinical implications

Myelodysplastic syndromes (MDS) are a heterogenous group of myeloid neoplasms that develop primarily in elderly patients. Although a specific molecular basis for the predominant incidence of MDS in higher age groups remains unknown, several lines of evidence suggest that the biology of aging and the pathogenesis of MDS share several genetic, epigenetic, and molecular features. The current review attempts to delineate these common aspects as well as additional discriminative features that are specific for MDS and thus help explaining disease-evolution and progression. In addition, the present review discusses age as an important prognostic factor and co-variable to be considered in treatment algorithms in MDS.     

Cannabinoids, endocannabinoids, and cancer

The endocannabinoid system consists of an array of endogenously produced bioactive lipids that activate cannabinoid receptors. Although the primary focus of endocannabinoid biology has been on neurological and psychiatric effects, recent work has revealed several important interactions between the endocannabinoid system and cancer. Several different types of cancer have abnormal regulation of the endocannabinoid system that contributes to cancer progression and correlates to clinical outcomes. Modulation of the endocannabinoid system by pharmacological agents in various cancer types reveals that it can mediate antiproliferative and apoptotic effects by both cannabinoid receptor-dependent and -independent pathways. Selective agonists and antagonists of the cannabinoid receptors, inhibitors of endocannabinoid hydrolysis, and cannabinoid analogs have been utilized to probe the pathways involved in the effects of the endocannabinoid system on cancer cell apoptosis, proliferation, migration, adhesion, and invasion. The antiproliferative and apoptotic effects produced by some of these pharmacological probes reveal that the endocannabinoid system is a promising new target for the development of novel chemotherapeutics to treat cancer.     

Selenium, lycopene, alpha-tocopherol, beta-carotene, retinol, and subsequent bladder cancer

To examine the association between serum nutrients and the development of bladder cancer we measured selenium, alpha-tocopherol, lycopene, beta-carotene, retinol, and retinol-binding protein in serum collected from 25,802 persons in Washington County, MD, in 1974. Serum samples were kept frozen at -70 degrees C. In the subsequent 12-year period, 35 cases of bladder cancer developed among participants. Comparisons of serum levels in 1974 among cases and two matched controls for each case showed that selenium was significantly lower among cases than controls (P = 0.03), lycopene was lower among cases at a borderline level of significance (P = 0.07), and alpha-tocopherol was nonsignificantly lower (P = 0.13). For selenium there was a nearly linear increase in risk with decreasing serum levels (P = 0.03). When examined by tertiles, the odds ratio associated with the lowest tertile of selenium compared to the highest tertile was 2.06. Serum levels of retinol, retinol-binding protein, and beta-carotene were similar among cases and controls. These results support a role for selenium in the prevention of bladder cancer.     

Clinical trial discussion, referral, and recruitment: physician, patient, and system factors

Purpose

Patient participation in cancer clinical trials is imperative to the advancement of medical science. Physicians play an important role in recruitment by discussing clinical trials with their cancer patients. Patient–physician discussion is influenced by many factors relating to the physician, the patient, and the healthcare system.

Methods

Physicians selected from the 2008–2009 American Medical Association Physician Masterfile who practiced in California, Florida, Illinois, or New York and specialized in medical oncology, surgery, or radiation oncology were surveyed about their attitudes and practices with respect to breast cancer clinical trials. Practice types were categorized according to the classifications provided by the American College of Surgeons, and clinical trial and practice addresses were geocoded.

Results

Surveys were completed by 706 of 1,534 eligible physicians (46 %). Medical oncologists were more likely than surgical or radiation oncologists to discuss the possibility, benefits, and risks of clinical trial enrollment with their breast cancer patients. Physicians who spent the most time in patient care were least likely to discuss clinical trials with their patients. Distance from a physician’s practice to the nearest clinical trial site was inversely associated with referral and recruitment. Perceived barriers to clinical trial participation were associated with greater referral activity suggesting that physicians who were more involved in trials were also more likely to understand barriers to participation.

Conclusions

Multilevel interventions may be successful at increasing participation of women in clinical trials.     

Tattoos, inks, and cancer

The introduction in the dermis of exogenous pigments and dyes to obtain a permanent design (tattooing) represents a unique in-vivo situation, where a large amount of metallic salts and organic dyes remain in the skin for the lifetime of the bearer. The potential local and systemic carcinogenic effects of tattoos and tattoo inks remain unclear. Several studies have shed light on the presence of potential carcinogenic or procarcinogenic products in tattoo inks. We extensively reviewed the literature and found 50 cases of skin cancer on tattoos: 23 cases of squamous-cell carcinoma and keratoacanthoma, 16 cases of melanoma, and 11 cases of basal-cell carcinoma. The number of skin cancers arising in tattoos is seemingly low, and this association has to be considered thus far as coincidental.     

Cancer, coagulation, and anticoagulation

Thromboembolic disease affects about 15% of cancer patients and presents a challenge to the oncologist for both prophylaxis and treatment. Although long known to be associated with malignancy, the underlying biochemical mechanisms are poorly understood. Both low-dose warfarin and low molecular weight heparin are effective strategies for prophylaxis of venous thromboembolism, including those involving venous access devices. Current treatment options for venous thromboembolism include heparin (unfractionated and low molecular weight), warfarin, and internal vena cava filters. The appropriate use of these therapeutic options in cancer patients is reviewed herein. There is suggestive evidence that heparin may be superior to warfarin in the long-term treatment of venous thromboembolism. Whether anticoagulants might also improve cancer survival rates independent of their effect on thromboembolism deserves further investigation.     

Appendectomy,tonsillectomy, and neoplasia

Reports in the literature that study the frequency of cancer in individuals who have had their tonsils or appendix or both removed are reviewed. Some investigators found a high incidence of solid cancers—in particular, breast and colon neoplasms—in female patients who have had appendectomy, but others disagreed. The association of tonsillectomy and/or appendectomy with the later development of malignant lymphomas is not proven.