Incidence of hand-foot syndrome with capecitabine in combination with chemotherapy as first-linetreatment in patients with advanced and/or metastatic gastric cancer suitable for treatment with a fluoropyrimidine-based regimen

INTRODUCTION: Hand-foot syndrome (HFS) is a limiting toxicity of capecitabine, which is not life-threatening but could compromise capecitabine efficacy. MATERIALS AND METHODS: This phase II, multicenter, non-controlled study assessed the safety, particularly grade three HFS incidence, and efficacy of four capecitabine-based chemotherapy regimens [cisplatin/capecitabine (CX), epirubicin/cisplatin/capecitabine (ECX), epirubicin/oxaliplatin/capecitabine (EOX) and docetaxel/cisplatin/capecitabine (DCX)] as first-line treatment for advanced and/or metastatic gastric cancer. RESULTS: One hundred and eight patients were assigned to one of the four treatment groups, according to investigator's criteria, and grouped together for both safety and efficacy primary analyses. HFS was reported in 31 patients (19.6%) and its first presentation occurred at a median of 72 days (range 19-209 days). Grade 3 HFS developed in 6.3, 5.2, 3.7 and 2.4%, of patients receiving ECX, DCX, EOX or CX chemotherapy regimen, respectively. Capecitabine dose reduction/discontinuation due to HFS was required in 5.7% of patients (9/158). The most common (> 10%) grade 3-4 treatment-related AEs were neutropenia (15.2%), asthenia (12.0%) and diarrhoea (11.4%). CONCLUSIONS: A moderate incidence of HFS was reported in patients treated with capecitabine, which generally presented late and required dose reduction in < 1/3 of patients. The results suggest that capecitabine may be useful in combination with standard fluorouracil-based regimens in patients with advanced and/or metastatic gastric cancer with favourable safety profile (AU)

Adjuvant radiochemotherapy in the treatment of completely resected, locally advanced gastric cancer.

PURPOSE: To analyze the efficacy and toxicity of adjuvant whole abdomen irradiation (WAI) and concomitant chemotherapy in the treatment of completely resected, high-risk gastric cancer. METHODS AND MATERIALS: Between October 1990 and September 1997, 52 patients with completely resected gastric cancer, with lymph node and/or serosal involvement, were treated. Ages were 16-78 (median, 53.5) years. Treatment was either total- or sub-total gastrectomy, followed by WAI, 2100 cGy/21 fractions plus a 2400 cGy/16 fractions boost to the tumor bed. Chemotherapy consisted of either 5-fluorouracil (5-FU) 450-500 mg/m(2) i.v. for 5 days first and 5th week or 200-300 mg/m(2) continuous infusion during irradiation. No further chemotherapy was given. RESULTS: With a minimum follow-up of 30 months and a median follow-up of 43.5 months, 25 of the 52 patients have died. Overall 5-year survival rate is 54%. Three patients sustained Grade 3-5 complications. Two patients with Grade 5 complications (malabsorption syndrome) died 31 and 56 months after the beginning of the treatment, respectively, with no evidence of recurrent tumor. For patients with involvement of the lymph nodes alone (n = 19) the 5-year survival was 69%, which was significantly better than the 36% 5-year survival observed for those patients with both serosal and lymph node involvement (n = 26, p = 0.004). CONCLUSION: Adjuvant radiochemotherapy, WAI, and concomitant 5-FU, is a feasible and a fairly well-tolerated treatment for patients with locally advanced (involvement of the lymph nodes or serosa) gastric carcinoma who undergo complete resection. The 54% overall 5-year survival compares favorably with the survival reported after surgery alone for those patients.

The impact of a multidisciplinary breast cancer center on recommendations for patient management: the University of Pennsylvania experience.

BACKGROUND: Advances in the diagnosis and treatment of breast carcinoma have led to a multidisciplinary approach to management for patients with breast carcinoma. To assess the effect of this approach, the authors performed an evaluation for a cohort of patients examined in a multidisciplinary breast cancer center. METHODS: An analysis was performed for the records of 75 consecutive women with 77 breast lesions examined in consultation in a multidisciplinary breast cancer center between January and June 1998. Each patient's case was evaluated by a panel consisting of a medical oncologist, surgical oncologist, radiation oncologist, pathologist, diagnostic radiologist, and, when indicated, plastic surgeon. A comprehensive history and physical examination was performed, and the relevant mammograms, pathology slides, and medical records were reviewed. Treatment recommendations made before this evaluation were compared with the consensus recommendations made by the panel. RESULTS: For the 75 patients, the multidisciplinary panel disagreed with the treatment recommendations from the outside physicians in 32 cases (43%), and agreed in 41 cases (55%). Two patients (3%) had no treatment recommendation before consultation. For the 32 patients with a disagreement, the treatment recommendations were breast-conservation treatment instead of mastectomy (n = 13; 41%) or reexcision (n = 2; 6%); further workup instead of immediate definitive treatment (n = 10; 31%); treatment based on major change in diagnosis on pathology review (n = 3; 9%); addition of postmastectomy radiation treatment (n = 3; 9%); or addition of hormonal therapy (n = 1; 3%). CONCLUSIONS: The multidisciplinary breast cancer evaluation program provided an integrated program in which individual patients were evaluated by a team of physicians and led to a change in treatment recommendation for 43% (32 of 75) of the patients examined. This multidisciplinary program provided important second opinions for many patients with breast carcinoma.

Factors predicting severe radiation pneumonitis in patients receiving definitive chemoradiation for lung cancer.

PURPOSE: To identify factors that may predict for severe radiation pneumonitis or pneumonopathy (RP), we reviewed a set of simple, commonly available characteristics. METHODS AND MATERIALS: Medical records of 148 lung cancer patients with good performance status (ECOG 0-1) treated definitively with chemoradiation from 6/92-6/98 at the University of Pennsylvania were reviewed. Actuarial survival and the crude rate of severe radiation pneumonitis were determined as a function of several variables. Potential predictive factors examined included age, gender, histology, stage, pulmonary function, performance status (0 vs. 1), weight loss, tumor location, radiation dose, initial radiation field size, chemotherapy regimen, and timing of chemotherapy. Univariate analysis (log-rank test) was performed for each variable. Multivariate analysis was performed using linear regression. RESULTS: Median survival for the entire cohort was 14.7 months. Four patients were inevaluable for pneumonitis due to early death from progressive disease. Of the remaining 144 evaluable patients, 12 (8.3%) experienced severe RP. The most significant factor predicting for severe RP was performance status (p < 0.003). The risk of severe RP was 16% for PS-1 patients vs. 2% for PS-0 patients. Women were significantly more likely to develop severe RP than men (p = 0.01). Among 67 patients for whom pre-radiation therapy pulmonary function data were available, forced expiratory volume of the lung in 1 second (FEV(1)) was also significant (p = 0. 03). No patient suffering severe RP had a pretreatment FEV(1) > 2.0 liters. The median radiation dose was 59.2 Gy and median initial radiation field size was 228 cm(2). Neither radiotherapy factor predicted for RP. Other factors studied, including chemotherapy drugs, and schedule, also were not significant predictors of severe RP. CONCLUSIONS: Pretreatment performance status, gender, and FEV(1) are significant predictors of severe radiation pneumonopathy, at least when using conventional radiation fields and doses. Complex radiation dose-volume algorithms that attempt to predict lung complication probabilities should probably incorporate these simply obtained clinical parameters.

Effect of Salmonella typhi wild type and O-antigen mutants on human natural killer cell activity.

We investigated the effect of glutaraldehyde-fixed Salmonella typhi Ty2 (Vi(-)) wild-type (World Health Organization's vaccine strain) and mutant strains MEI028 (rough, O-antigen(-)) and MEI012 [smooth (O-antigen(+)95%), immunomagnetically isolated NK cell preparations. Incubation of PBMC with each and every one of the S. typhi strains studied consistently and significantly, increased this cellular immune function, as well as the supernatant level of the various cytokines tested e.g. IFN-gamma, TNF-alpha, IL-10 and IL-12 (ELISA). In similar experiments, a significant increase in the cytolytic activity of HPNK cells was elicited by S. typhi Ty2 but not by mutant strain MEI028; neither of the cytokines assayed (IFN-gamma and TNF-alpha) was detected in the supernatant. Our results suggest that S. typhi O-antigen plays an essential role in a mechanism resulting in the direct activation of NK cell activity in HPNK cell preparations. However, the relative quantitative significance of this antigen in the direct stimulation of NK cell cytotoxicity expression in PBMC samples is less clear, as it appears that in this case bacterial-induced monocyte-released cytokines plays a most important role. Incubation with S. typhi Ty2 or MEI028 elicited significant expression of CD69, an early marker of NK cell activation, in PBMC but not in HPNK cell samples (flow cytometry); in similar experiments, the expression of CD16/56 and activation marker CD25 remained essentially unchanged.

[Radiotherapy in the treatment of non-small-cell lung cancer]. / Radioterapia en el tratamiento del cáncer pulmonar de células no pequeñas.

The results of curative radiotherapy in 59 patients with non-small-cell carcinoma of the lung treated from 1977 to 1988 are reported. Squamous cell carcinoma without evidence of metastatic disease was present in 28 patients. Radiotherapy alone was used in 43 patients; 13 patients received either pre or post operative radiotherapy. Complications developed in 6 patients, only 1 had esophageal stenosis deemed important. The first site of failure was extrathoracic in 76% of patients, the brain being the most frequently involved site (41%). Brain failure rate was greater for squamous cell carcinoma than for other tumors. The 5 year survival rate was 20% with a minimum follow up period of 24 months (median 57). Better results were obtained in patients receiving high dose continuous radiotherapy and in those with associated surgery. Thus, radiotherapy is an alternative therapy for patients with lung carcinoma, with a reasonable survival rate and few complications.

The effect of sexual behavior and a pregnancy on contraceptive method switching among black female teens.

Little is known about determinants of contraceptive method switching and few reports use data that can link events that occur close in time. Using retrospective information from the sexual calendars of black female teens who attended a reproductive health clinic, determinants of method switching in four areas were investigated. Method switchers, those who switched from an unprepared to a prepared method (n = 62) and those who switched from a prepared to an unprepared method (n = 18), were matched with nonswitchers who used the same initial method. Associations between switching and changes in the frequency of intercourse, sexual abstinence, and pregnancy were found. It is suggested that abstinence may have a different role in switching from each type of method. Counselors need to emphasize the importance of method continuation, even when sex has not occurred for a short period of time.

PIP: Little is known about determinants of contraceptive method switching and few reports use data that can link events that occur close in time. Using retrospective information from the sexual calendars of black female teens who attended a reproductive health clinic in a US urban center, determinants of method switching in 4 areas were investigated. Method switchers, those who switched from an unprepared to a prepare method (n = 62) and those who switched from a prepared to an unprepared method (n = 18), were matched with nonswitchers who used the same initial method. Associations between switching and changes in the frequency of intercourse, sexual abstinence, and pregnancy were found. It is suggested that abstinence may have a different role in switching from each type of method. Counselors need to emphasize the importance of method continuation, even when sex has not occurred for a short period of time.