Nasion Swelling as the Presenting Symptom of Lung Adenocarcinoma

AbstractMetastasis to the paranasal sinuses from lung cancer is extremely rare. Here, we reported a patient of lung adenocarcinoma presenting with nasion swelling because of metastasis to the paranasal sinuses. A review of the literature from 1966 to 2008 yielded another 15 patients. Adenocarcinoma was the most commonly encountered histologic subtype, and modern combination chemotherapy was probably the most effective treatment modality. Headache, visual disturbance, facial mass, and facial pain were the symptoms frequently associated with paranasal sinus metastasis; however, all of them were nonspecific for a metastatic tumor. A thorough history taking, ear, nose, and throat examination, and laboratory investigations are of paramount importance to achieve a correct diagnosis

Pemetrexed in combination with cisplatin versus cisplatin monotherapy in E ast A sian patients with recurrent or metastatic head and neck cancer: Results of an exploratory subgroup analysis of a phase III trial

Aim: An exploratory subgroup analysis of E ast A sian ( EA ) patients in a phase III trial was conducted to assess efficacy and safety trends based on ethnicity. Methods: The 795 patients with recurrent or metastatic squamous cell carcinoma of the head and neck included 111 EA patients randomized to pemetrexed‐cisplatin ( n  = 55) and placebo‐cisplatin ( n  = 56) and 684 non‐ EA patients randomized to pemetrexed‐cisplatin ( n  = 343) and placebo‐cisplatin ( n  = 341). Treatment differences in median overall survival and progression‐free survival were compared using a stratified log–rank test. Survival was estimated using the K aplan– M eier method. Results: The median overall survival in the pemetrexed‐cisplatin and placebo‐cisplatin arms of the EA group (6.8 and 5.7 months, respectively [ P  = 0.275]) was similar to that in the global population (7.3 and 6.3 months, respectively [ P  = 0.082]); the median progression‐free survival in the pemetrexed‐cisplatin and placebo‐cisplatin arms in the EA group (2.8 and 1.9 months, respectively [ P  = 0.748]) was similar to that in the global population (3.6 and 2.8 months, respectively [ P  = 0.166]). Compared to the findings in the global population, overall survival for the EA group receiving prior platinum‐based therapy was longer ( P  = 0.042 vs P  = 0.065). There was no significant interaction between treatment arms and ethnicity. Conclusion: Consistent with findings in the global population, pemetrexed‐cisplatin did not improve survival compared with placebo‐cisplatin for the EA group . However, in a subgroup analysis, pemetrexed‐cisplatin showed an overall survival advantage in EA patients receiving prior platinum‐based therapy.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/101808/1/ajco12060.pd

Women with endometriosis have higher comorbidities: Analysis of domestic data in Taiwan

AbstractEndometriosis, defined by the presence of viable extrauterine endometrial glands and stroma, can grow or bleed cyclically, and possesses characteristics including a destructive, invasive, and metastatic nature. Since endometriosis may result in pelvic inflammation, adhesion, chronic pain, and infertility, and can progress to biologically malignant tumors, it is a long-term major health issue in women of reproductive age. In this review, we analyze the Taiwan domestic research addressing associations between endometriosis and other diseases. Concerning malignant tumors, we identified four studies on the links between endometriosis and ovarian cancer, one on breast cancer, two on endometrial cancer, one on colorectal cancer, and one on other malignancies, as well as one on associations between endometriosis and irritable bowel syndrome, one on links with migraine headache, three on links with pelvic inflammatory diseases, four on links with infertility, four on links with obesity, four on links with chronic liver disease, four on links with rheumatoid arthritis, four on links with chronic renal disease, five on links with diabetes mellitus, and five on links with cardiovascular diseases (hypertension, hyperlipidemia, etc.). The data available to date support that women with endometriosis might be at risk of some chronic illnesses and certain malignancies, although we consider the evidence for some comorbidities to be of low quality, for example, the association between colon cancer and adenomyosis/endometriosis. We still believe that the risk of comorbidity might be higher in women with endometriosis than that we supposed before. More research is needed to determine whether women with endometriosis are really at risk of these comorbidities

A Phase-I Study Evaluating the Combination of Pegylated Liposomal Doxorubicin and Paclitaxel as Salvage Chemotherapy in Metastatic Breast Cancer Previously Treated with Anthracycline

Purpose The two main goals of this phase-I study were to determine the maximum-tolerated dose (MTD) and to characterize the toxicity of the combination of pegylated liposomal doxorubicin (PLD; Lipo-Dox) and paclitaxel (PTX) administered on a 3-week schedule in patients with metastatic breast cancer (MBC) who had previously been treated with anthracycline-based therapy. Methods This phase -I study was performed via a two-staged dose escalation schema. The initial doses were PLD 30 mg/m(2 ) and PTX 150 mg /m(2), administered intravenously once every 21 days. The dose of PLD was escalated in increments of 5 mg/m(2) until the MTD was reached, at which time the PTX was then increased in increments of 10 mg/m (2) until the MTD was reached. Results Twenty-three patients received between 1 and 13 treatment cycles. In stage I of the study, 14 patients received a fixed dose of PTX 150 mg/m(2) while PLD escalated from 30 mg/m( 2). At 40 mg/m(2), PLD resulted in dose-limiting toxicities (DLT) including febrile neutropenia and palmar-plantar erythrodysesthesia that occurred in two of five patients. In stage II of the study, nine patients received fixed dose of PLD 35 mg/m(2) and escalating doses of PTX starting at 160 mg/m(2). At PTX 170 mg/m(2) and dose- limiting neutropenic fever occurred in two of five patients . Out of 19 evaluable patients, 10 (52.6% ) achieved objective response (one complete response and nine partial response), and 5 had stable disease. Conclusions The maximal tolerated doses of PLD and PTX are 35 and 160 mg/m(2), respectively, administered every 3 weeks. The combination of PLD (30-35 mg/m(2)) and PTX (150-160 mg/ m(2)) constitutes an active regimen with mild toxicity that merits further study

Phase I and Pharmacokinetic Study of a Stable, Polyethylene-Glycolated Liposomal Doxorubicin in Patients with Solid Tumors - the Relation between Pharmacokinetic Property and Toxicity

BACKGROUND. Compared with free drug, sterically stabilized liposomal drug has prolonged circulation time and, thereby, higher tumor selectivity and antitumor activity. The stability in plasma is an important consideration in the formulation of clinically useful liposomal drug. A Phase I study of a stable liposomal doxorubicin with polyethylene glycol (PEG) coating and phospholipid component of distearoyl phosphatidylcholine (DSPC) was performed to characterize its pharmacokinetic properties, toxicity profile , and maximal tolerated dose. METHODS. The starting dose was 30 mg/m(2) every 3 weeks with an increment of 10 mg /m(2) for each level. A cohort of at least three patients was entered for each level. Dose escalation stopped when more than one-third of patients had dose limiting toxicity ( DLT), which was equal to or more than Grade 3 nonhematologic toxicity. Blood was sampled immediately before and at 5 minutes, 2 hours, 4 hours, 10 hours, 24 hours, 48 hours, 72 hours, and 168 hours after the completion of PEGylated liposomal doxorubicin (PLD) infusion. Plasma level of doxorubicin was determined with fluorometry, and the pharmacokinetic properties were analyzed. RESULTS. Twenty- six patients were entered. and 101 courses were studied. This DSPC PLD had a steady-state distribution volume (Vss) of 2.4 +/- 0.9 liters (mean +/- standard deviation), a clearance of 0.027 +/- 0.010 liters per hour, and a beta half-life of 65.0 +/- 17.8 per hour. These characteristics were dose independent, and the Vss and clearance were smaller than those of a well characterized PLD comprised of hydrogenated soybean phosphatidylcholine (HSPC). At the dose level of 50 mg/m2, its plasma area under the concentration time curve was approximately twice that of HSPC PLD. Attenuation of acute toxicity, such as nausea, emesis, and alopecia, was noted in all dose levels. However, stomatitis was common from the dose level of 30 mg/m(2), and its incidence and severity increased with dosage and became dose limiting at 50 mg/m2. A dose of 45 mg/m(2) every 3 weeks was then given in eight patients, and the side effects were acceptable. This dose was recommended for Phase II clinical trials. Fourteen of 17 patients with a dose level greater than or equal to 40 mg/m2 were evaluable for response, but none achieved partial remission. CONCLUSIONS. This DSPC PLD had the characteristics of second- generation liposomal drug pharmacokinetically and toxicologically. The incidence of severe stomatitis was higher than that of HSPC PLD, corresponding to the difference in pharmacokinetics. Only limited antitumor activity was observed, although defining its therapeutic application will need further Phase II studies. Further prolongation of plasma stability of PLD may not be clinically beneficial considering the increased stomatitis and the reduced achievable dose intensity. (C) 2001 American Cancer Society

Induction with Mitomycin C, Doxorubicin, Cisplatin and Maintenance with Weekly 5-Fluorouracil, Leukovorin for Treatment of Metastatic Nasopharyngeal Carcinoma: A Phase Ii Study

The combination of cisplatin and 5-fluorouracil (5-FU) (PF) is the most popular regimen for treating metastatic nasopharyngeal carcinoma (NPC) but it is limited by severe stomatitis and chronic cisplatin-related toxicity . A novel approach including induction with mitomycin C, doxorubicin and cisplatin (MAP) and subsequent maintenance with weekly 5 -FU and leucovorin (FL) were designed with an aim to reduce acute and chronic toxicity of PF. Thirty-two patients of NPC with measurable metastatic lesions in the liver or lung were entered into this phase 11 trial. Mitomycin C 8 mg m 2, doxorubicin 40 mg m-1 and cisplatin 60 mg m 2 were given on day 1 every 3 weeks as initial induction. After either four courses or remission was achieved, patients received weekly dose of 5-FU 450 mg M-2 and leucovorin 30 mg M-2 for maintenance until disease progression. With 105 courses of MAP given, 5% were accompanied by grade 3 and 0% were accompanied by grade 4 stomatitis. The dose-limiting toxicity of MAP was myelosuppression. Forty per cent of courses had grade 3 and 13 % of courses had grade 4 leukopenia. No grade 3 or 4 cisplatin-related toxicity was observed. The overall response rate was 94% (95% confidence interval (CI) 84.9-100%) with a complete response rate (CR) of 6% (95% Cl: 0-15.2%) and a good partial response (PR) rate of 28% (95% Cl 11.7-44.6%) , which was optionally defined as observance of only equivocal lesion identifiable under imaging study. Twenty-seven cases entered weekly FL maintenance phase. The median duration of maintenance with weekly FL was 38 weeks (8-91 weeks). There was no grade 3 or 4 toxicity noted during weekly FL. The median progression- free survival and overall survival were 11.6 + 0.4 and 18.1+ 3.6 months respectively. Six patients with a median follow- up of 19.8 months (9.6-41.0 months) were still alive and five of them had disease under control with FL. Good responders (CR and good PR) had better survival than less satisfactory responders (PR and stable disease) (P = 0.05). From Cox's multivariate regression analysis, the only significant prognostic factor for survival was good response to MAP (P = 0.042). Liver metastasis was the only significant variable in the best subset regression model that predicted good response to MAP (CR and good PR) (P = 0. 027). MAP was an effective combination for metastatic NPC with minimal stomatitis and cisplatin-related toxicity but had significant myelosuppression. Weekly FL was a maintenance therapy with minimal side- effects. The response rate and overall survival of MAP-FL were better than series previously reported even when a subset of patients with poor prognosis was selected. MAP-Fus role as neoadjuvant or adjuvant therapy is worthy of further study