Antianemic effect of once weekly regimen of epoetin alfa 40,000 units in anemic cancer patients receiving chemotherapy.

BACKGROUND: Anemia is a common problem in the cancer population that is the result of clinical consequences. It also has adverse effects on patients' perceived quality of life. Good management of anemia in the cancer population is therefore essential. A recent published clinical trial has demonstrated statistically significant increases in hemoglobin levels and significantly increased QOL assessment following the administration of recombinant erythropoietin. OBJECTIVE: To evaluate the effectiveness, the safety, and the quality of life by using once weekly dosing of Epoetin alfa (Eprex, Janssen-cilag) 40,000 units in the treatment of anemia in cancer patients receiving chemotherapy. SETTING: Division of Medical Oncology, Department of Medicine, Faculty of Medicine, Chulalongkorn University Bangkok, Thailand. MATERIAL AND METHOD: This was an open label, non-randomized study, in 41 adult male and female anemic cancer patients who had non-myeloid malignancies in the upper area of the body part and hemoglobin ranging from 9-11 g/dL receiving chemotherapy at least 8 weeks with or without concurrent radiotherapy. The subjects were treated with Epoetin alfa 40,000 units once a week subcutaneously. If, the hemoglobin did not increase by > 1.0 g/dl after 4 weeks of treatment, the dose of Epoetin alfa was then increased to 60,000 units per dose subcutaneously at week 5. The Epoetin alfa treatment would continue for a total of 16 weeks. Clinical outcome was evaluated based on quality of life by using the linear analog scale assessment (LASA) and the functional assessment of cancer therapy-anemia (CU-QOL) instrument. Analyses were performed to determine the incremental change in QOL associated with hemoglobin increases. RESULTS: Seventy six percent of patients receiving Epoetin alfa subcutaneously showed good response with hemoglobin increases of > or = 1 g/dL (Hb level before and after = 9.82 +/- 0.78 g/dL and 12.56 +/- 1.49 g/dL, respectively; p < 0. 001). Improvement of all primary cancer- and anemia-specific QOL domains, including energy level and ability to do daily activities evaluated from LASA and fatigue assessed from CU-QOL, were significantly greater (p < 0.01) for week 16 (233.94 +/- 56.01 and 18.45 +/- 13.07) compared to the baseline (202.58 +/- 36.74 and 25.09 +/- 11.00). Epoetin alfa was well tolerated in all patients. CONCLUSION: Once weekly dosing of Epoetin alfa 40,000 units therapy is safe and effective in remodeling anemia and significantly improves the quality of life in cancer patients receiving chemotherapy. Therefore, the physician should maintain hemoglobin concentration of cancer patients in normal level to improve their quality of life through the chemotherapy period.

Phase II trial of ramosetron plus dexamethasone in the prevention of cisplatin-induced nausea and vomiting.

OBJECTIVE: To evaluate the clinical efficacy of ramosetron hydrochloride in the combination with dexamethasone for the prevention of nausea and vomiting induced by cisplatin. MATERIAL AND METHOD: Thirty in-patients with malignant tumor being treated with cisplatin at a dose of 70 mg/m2 or more for a total of 94 cycles were scheduled to receive ramosetron 0. 3 mg IV given 30 minutes before chemotherapy and dexamthasone 20 mg IV on day 1 for the prevention of acute emesis and continued with ramosetron tablet 0.1 mg one tablet orally one hour before chemotherapy or in the morning in case of no chemotherapy scheduled and dexamethasone capsule 5 mg 2 capsules twice daily on day 2 to day 5 for the prevention of delayed emesis. The evaluation period started concomitantly with the start of chemotherapy (hour 0) and continued until 24 hours after completion of chemotherapy. The antiemetic efficacy of ramosetron plus dexamethasone was analyzed according to the occurrence of nausea and vomiting within 24 hours of treatment cycle. The study emphasized both on acute and delayed emesis control. ASSESSMENT: The degree of severity of nausea was determined according to the following criteria: 0: None: nausea does not occur, 1: Mild: slight nausea but no disruption to daily acitivites, 2: Moderate: nausea and some disruption to daily activities, 3: Severe: extreme nausea and severe disruption to daily activities. The control of vomiting episodes was determined according to the frequency of vomiting (including retching) as the following criteria: Complete: 0 emesis episode, Major: 1-2 emesis episodes, Minor: 3-5 emesis episodes, Failure: > 5 emesis episodes. RESULTS: The result of all 94 cycles of the first day of treatment on acute emesis (0-24 hours) were none 80.9%, mild 18.1%, and moderate 1.1% for nausea episode. For the vomiting control were complete 81.9%, major 16%, minor 1.1% and failure 1.1% respectively. The efficacy of the prevention of delayed emesis (day 2 to day 5) for nausea episode were 67%, 66%, 70.2%, and 75.5% no nausea respectively. For the vomiting control were 75.5%, 74.5%, 86.2%, and 88.3% complete control on day 2 to day 5. No serious adverse events occurred. Hiccups, constipation, and dull headache were reported as the common side effects of ramosetron. CONCLUSION: Ramosetron combined with dexamethasone is effective for the prevention of both acute and delayed emesis associated with cisplatin. The prevention of acute emesis seems to be more effective than the prevention of delayed emesis. Adverse events were mild. No serious side effects occurred in the present study.

Histopathologic characteristics of pulmonary adenocarcinomas with and without EGFR mutation.

EGFR mutation played crucial role for responsiveness of non-small cell lung cancers to EGFR tyrosine kinase inhibitors. Almost the mutations were present in adenocarcinomas. Few had studied on histopathologic correlation with EGFR mutation in pulmonary adenocarcinomas. To obtain better view on pathobiology of pulmonary adenocarcinomas, we correlated exons 19 and 21 mutations with various histopathologic features by dissecting particular histological patterns from 60 surgically resected adenocarcinomas. RESULTS: Gland-forming pattern, including bronchiloloalveolar carcinoma (BAC), well-formed acinar, and poorly-formed acinar patterns more frequently contains EGFR mutations than solid pattern (72.7% vs. 23.1%, p = 0.002). EGFR mutations of each within the gland-forming pattern are not significantly different. Micropapillary pattern revealed less exon 19 mutations than the gland-forming pattern (12.5% vs. 66.7%, p = 0.018), but tended to have more Exon 21 mutations than the others (33.3% vs. 11.9%, p = 0.10). Tumors predominated by BAC pattern more commonly had exon 19 mutations than non-BAC predominated tumors (68.8% vs. 39.5%, p = 0.046). EGFR-mutated tumors comprised less proportion of papillary pattern than tumors without mutation (mean = 1.5% vs. 11.2%, p = 0.049). Terminal respiratory unit (TRU) histology was associated with more EGFR mutations (72.4% vs. 42.1%, p = 0.036). Tumors smaller than 3.5 cm had more EGFR mutations than larger tumors (73.1% vs. 41.9%, p = 0.018). CONCLUSION: High frequency of the mutation does not present only in BAC pattern, but also in well-formed and poorly-formed acinar patterns, suggesting them as usual spectrum of EGFR mutated adenocarcinomas. Other characteristics of EGFR-mutated adenocarcinomas include TRU-type histology, smaller size, and less solid phenotype.

Clinical benefits of epoetin alfa (Eprex) 10,000 units subcutaneously thrice weekly in Thai cancer patients with anemia receiving chemotherapy.

BACKGROUND: Recently the American society of clinical oncology and the American society of hematology have jointly launched the clinical practice guideline of epoetin usage in cancer related anemia patients The recommended starting dose is 150-300 unit/kg thrice weekly. The clinical outcome of epoetin alfa 10,000 units subcutaneously thrice weekly regimen has not been evaluated in Thai cancer patients with anemia yet. OBJECTIVES: To determine the clinical benefits and safety of epoetin alfa (Eprex) 10,000 units subcutaneously thrice weekly in anemic cancer patients receiving chemotherapy PATIENTS: The present study was an open label, non-randomized study. Adult patients were eligible for inclusion aged >18 years with a confirmed diagnosis of non-myeloid malignancy in the upper area of the body and scheduled to receive chemotherapy regardless of the concurrent radiotherapy. All patients had hemoglobin (Hb) level less than 11 g/dL, serum ferritin more than 100 ng/dL and had a life expectancy of at least 6 months. MATERIAL AND METHOD: All patients were initially treated with Epoetin alfa 10,000 units subcutaneously thrice weekly. The dose was up to 20,000 units after 4 weeks of therapy, if Hb level did not increase by > 1.0 g/dL. Treatment time was 16 weeks. Target Hb was 12 g/dL Blood transfusion and iron supplement was permitted. Efficacy Assessments: The primary efficacy end point was the proportion of responders (patients with an increase in Hb > or =1 g/dL). Secondary efficacy evaluation was change in Quality of life (QOL) scores by the Linear Analog Scale Assessment (LASA) and Quality of life-Chula (QOL-CU) scale. Statistical Analysis was t-tests, P < 0.05 was considered significant. RESULTS: Forty patients (21 men and 19 women) were enrolled. Twenty five patients (62.5%) had stage of disease in grade III or IV The mean Hb levels at baseline were 8.46 +/- 1.28 g/dL. Eight patients (20%) refused to complete the course during the study. Reasons for refusing to participate included lack of time, changing the resident area or disease progression. Twenty three of 32 patients (71.8%) were responders. These patients completed the study course and showed good response. Their mean Hb levels increased gradually and reach approximately 11 g/dl by week 4 and were maintained through week 16. The significant difference in mean Hb level of baseline was initially found at week 4 of the study (10.26 +/- 1.95 g/dl; p = 0.001 vs baseline). The LASA score increased in all of three items including level of energy, ability to do daily activities, and overall QOL but not statistical significance. However, the improvement of quality of life of cancer patients, evaluated by QOL-CU, was significantly apparent after treatment, (p < 0.05). The most common adverse events were grade I flu like symptoms (17.5%) and recovered the next day. CONCLUSION: Epoetin alfa (Eprex) 10,000 units thrice weekly significantly increased the hemoglobin levels, achieving the target hemoglobin and sustained the level in cancer patients with anemia receiving chemotherapy. Clinical benefits on functional status and quality of life were also improved. The treatment was well tolerated.

Pattern of local-regional recurrence in patient with early breast cancer after mastectomy: an analysis of 357 cases at King Chulalongkorn Memorial Hospital.

A retrospective review was performed on 357 patients with early stage I-IIIA operable breast cancer who were treated with mastectomy and referred to the clinic at the Division of Radiation Therapy, Department of Radiology, King Chulalongkorn Memorial Hospital between Jan 1991 and Dec 2001. Patients characteristics, treatment modalities and pattern of local and regional failure were evaluated. The median and mean age in the present study were 49 and 50.2 years, respectively. Stage I, II and IIIA were 10.9%, 79.6% and 9.5%, respectively. One hundred and ninety-seven patients (55.2%) received postoperative radiation therapy (RT). Adjuvant chemotherapy was given in 247 patients (69.2%) while 122 patients (34.2%) received adjuvant hormonal therapy. Sixty one patients (17.1%) received both adjuvant chemotherapy and hormonal therapy. However, 12.6% (45/357) did not receive any adjuvant treatment. Median follow up time was 42.6 months (range 6-136 months). Ipsilateral supraclavicular node and chest wall were the most common sites of local-regional recurrence. The chest wall recurrence rate was 10.4% (37/357), which was 16.9% (27/160) in the non postoperative radiation (No RT) group and 5.1% (10/197) in the postoperative radiation (RT) group. For ispilateral supraclavicular node, the recurrence rate was 10.6% (38/357), which was 15.6% (25/160) and 6.6% (13/197) for non RT and RT groups, respectively. The incidence of ipsilateral axilla, ipsilateral internal mammary node and ipsilateral infraclavicular node recurrence rate were 4.2%, 3.6% and 0.8%, respectively. Overall, chest wall and ipsilateral supraclavicular node were the most common sites of local-regional recurrence in early stage operable breast cancer who underwent mastectomy Postoperative adjuvant radiation therapy decreased the risk of local-regional recurrence.