phase 2 study of the combination of gemcitabine and cisplatin in patients with locally advanced or metastatic breast cancer previously treated with anthracyclines with/ without taxanes

Many patients with relapsed metastatic breast cancer are pre-treated with taxanes and anthracyclines, which are usually given in the neoadjuvant/adjuvant setting or as first-line treatment for metastatic disease. The primary objective of this study was to determine the overall response rate for combination treatment with gemcitabine and cisplatin in patients with locally advanced or metastatic breast cancer who had relapsed after receiving one adjuvant/neoadjuvant or first-line metastatic chemotherapy regimen containing an anthracycline with/without a taxane. Secondary endpoints included duration of response, time to progression, one-year survival probability, and toxicity. A single-arm, open-label, phase 2 study conducted at 1 7 investigative sites in Egypt. Treatment consisted of gemcitabine [1250 mg/m[2]] on Days 1 and 8 and cisplatin [70 mg/m[2]] on Day 1 of each 21-day cycle. Treatment continued until disease progression or a maximum of 6 cycles. Of 144 patients all were evaluable for safety and 132 patients were evaluable for efficacy. The overall response rate was 33.3% and 45.5% of the patients with stable disease as their best response. The median time to progression was 5.1 months and the one-year survival probability was 73%. The most common grade 3/4 adverse events were nausea/vomiting [20.1%], neutropenia [19.4%], anemia [13.9%], asthenia [11.1%], diarrhea [9.7%], stomatitis [7.6%], leucopenia [7.6%], and thrombocytopenia [6.2%]. Twelve [8.3%] patients had serious adverse events. The results of this study indicate that gemcitabine and cisplatin were active and generally well tolerated in pretreated patients with locally advanced or metastatic breast cancer

phase II study of gemcitabine combined with vinorelbine as first-line chemotherapy for metastatic breast cancer

There is an unmet need for new combination treatments, especially for aggressive, visceral, and high tumor burden metastatic breast cancer. Gemcitabine [GEM] has shown synergy with vinorelbine [VRL] in preclinical models, and has a toxicity profile that is different from VRL, another recently approved cytotoxic drug that seems to be effective in the treatment of breast cancer. We studied the efficacy and side effects of the GEM-VRL combination as first-line chemotherapy in patients in an openlabel, single arm, phase II study in patients with locally advanced or metastatic breast cancer who had been previously treated with an anthracycline-based regimen in the adjuvant/neoadjuvant setting. Of the 74 patients enrolled, 72 patients were evaluable for the primary treatment outcome [tumor response rates]. Four patients [6%] had a complete response and 26 patients [36%] had a partial response. Nineteen patients [26%] had stable disease. The median time to disease progression was 37 weeks [range, 1 -60 weeks]. Median duration of response was 43 weeks [range, 8.6 to 55 weeks] and one-year survival was 77% [95% confidence interval, 64% to 86%]. Grade 3-4 neutropenia without fever was reported in 10% of patients, thrombocytopenia in 1%, and febrile neutropenia in 11%. The most common clinical grade 3-4 toxicities were nausea [24%] and diarrhea and stomatitis [11% each]. Hospitalizations for adverse events mainly due to anemia, febrile neutropenia, septic shock and hepatic failure occured in 7%. With an overall response rate of 42%, the GEM-VRL combination had promising efficacy and good tolerability in metastatic breast cancer patients

Breast cancer services at Assiut University Hospital 2004: cost and quality issues

A study was undertaken at Assiut University Hospital in 2004 to describe the processes of service delivery to breast cancer patients and to provide an answer the following question. To what extent are breast cancer services offered cost effective? Cost was estimated by identifying all medical records of breast cancer patients at the General Surgery and at the Oncology Departments for listing the dates admission to inpatient as well as dates of discharge to compute inpatient days at the hospital. Patients receiving chemotherapy were identified from the archived one days admissions at the medical informatics department. The outpatient visits for radiotherapy were also identified from the Oncology Department register for radiotherapy. The WHO estimate of cost of hospital inpatient bed/day and outpatient visit including drugs and investigations was used to estimate the cost of services in Assiut University Hosptial. The estimated total cost of services for 2004 was 572,568 LE. For approximately 201 patients according to number of patients visiting the oncology outpatient for chemotherapy. The average cost /patient was 2848 LE. At each service point different numbers of breast cancer patients were receiving care. Some indirect measures point to the extremely poor stage of the disease for these women; notably more than 50% of the women receiving the radiotherapy are receiving it for palliative care, as they were me astatic patients. Effectiveness in term of survival was not possible to compute as medical records for inpatients are archived only for three years with the current expenditure levels, and lack of an information system can easily link elements and details of care provided with patient outcome, improvements in quality of care are not possible

Depressive phenomena and physical symptom distress among women with breast cancer and their impact on women's quality of life

Breast cancer accounts for about 30% of cancer deaths in women in developed countries and about 15% in developing countries. Breast cancer commonly produces depressive symptoms and physical symptoms distress which have a direct and profound impact in all aspects of quality of life. Therefore the study aimed to assess the nature and scope of depressive phenomena and physical symptoms distress in women after breast cancer diagnosis, to determine the relationship between depressive symptoms and physical symptom distress among breast cancer women, examine the relation of depression as well as physical symptom distress of patient's quality of life. A descriptive correlation design was used on the study sample which consisted of 50 female patients and 50 women who haven't cancer as a control group in total. The study was conducted at outpatient breast cancer clinic, at Assiut University Hospital. Socio- demographic data sheet was developed and used by the investigator in addition to quality of life questionnaire for women with advanced breast cancer which included four domains mobility impairment, GIT toxicity, bone pain and fatigue, Beck Depression Inventory Scale [BDI] and symptoms Distress Scale [SDS]. Results revealed that, depression is a common response to breast cancer in both its early and late stages. Most of breast cancer women suffer from moderate to sever symptom distress, there was a significant relation between depression and symptom distress and they had direct and indirect impact on quality of life among breast cancer women. It was recommended that, an educational training program should be provided to women with breast cancer to foster their potential rehabilitation and improve their quality of life

Efficacy of pre-operative chemotherapy and sequential radiation therapy in irresectable rectal carcinoma

To evaluate the toxicity and relative response rates of addition of cisplatin to 5-fluorouracil and leucovorin preoperative induction chemotherapy followed by local radiotherapy in irresectable rectal cancer and their impact on radical resectability and sphincter preservation. Between January 2002 and April 2006, 29 patients with locally advanced unresectable rectal cancer received two cycles of 5-fluorouracil 600mg/m[2], I.V 6h infusion D[1]-D[5] and D[22]-D[26], Leucovorin 20mg/m[2], I.V 1h infusion D[1]-D[5] and D[22]-D[26] and cisplatin [CDDP] 60mg/m[2], I.V 6h infusion D[1] and D[22] after good hydration. Radiation treatment was administered after two weeks of the second cycle of chemotherapy. The dose was 45 Gray in 25 fractions over 5 weeks prescribed at isocenter of the plan to include the rectum and the draining lymph node chains. Tumor dimensions were assessed by CT scan before the start and 4 weeks after chemoradiotherapy. Tumor response classification was based on the standard World Health Organization criteria. Complete response [CR] is complete disappearance of the disease. Partial response [PR] is a decrease of 50% of the sum of the products of the greatest perpendicular diameters [SPD]. Progressive disease [PD] is appearance of a new lesion or an increase of 25% in SPD. Stable disease [SD] is no change in SPD or a change not reaching PR or PD. Overall response rate [ORR] is CR plus PR. Our regimen was well tolerated. The main toxicity to it was grade II hematological and grade II and III GIT toxicities in 31% and 65.5% respectively. PR occurred in 58.6% [17/29], SD in 20.7% [6/29] and PD in 20.7% [6/26]. Anterior resection of the rectum with total mesorectal excision and sphincter preservation was done in 37.9% [11/29], abdomino-perineal resection in 31.05% [9/29] and palliative colostomy in 31.05% [9/29]. Radical resectability was achieved in 62.1% [18/29] and cytoreductive surgery in 6.9% [2/29]. After 2 years follow up of resected cases, the 2 years disease free survival was 60% [12/20] with 25% [5/20] local recurrence rate and 15% [3/20] distant metastases to the liver. Our pre-operative combined modality therapy seems to have potential advantage in tumor response, local control and sphincter preservation with tolerable acute and chronic toxicity. Sequential use of chemo-radiotherapy needs more studies to estimate the maximum tolerable dose of chemotherapy and radiotherapy with least side effects

Efficacy of pre-operative chemotherapy and sequential radiation therapy in unresectable rectal carcinoma

The aim of this study was to determine the extent of down staging, resectability rate, sphincter preservation and toxicity to preoperative chemotherapy with sequential radiation therapy in the treatment of locally advanced unresectable rectal carcinoma. Between January 2002 and February 2003, 29 patients with a diagnosis of locally advanced unresectable rectal cancer received two cycles of 5-fluorouracil 600 mg/m2, i.v. 6 hr infusion D1-D5 and D22-D26, leucovorin 20 mg/m2, i.v. 1 hr infusion DI-D5 and D22-D26 and cisplatin [CDDP] 60 mg/m2, i.v. 6hr infusion D1 and D22 after good hydration. Radiation treatment was administered after two weeks of the second cycle of chemotherapy. The dose was 45 Gray in 25 fractions over 5 weeks prescribed at iso-center of the plan to include the rectum and the draining lymph node chains. Tumor down-staging occurred in 11 out of 29 patients to whom abdominal resection with sphincter preservation was done and 9 patients with locally advanced rectal cancer were rendered operable and underwent abdominoperineal resection, while the rest of the patients remained inoperable. A total of 3 local recurrences out of 20 resected cases was developed within one year of follow up in the group of patients who underwent anterior abdominal resection, while distant metastases to the liver occurred in three patients whom were inoperable

Response of skeletal metastases to systemic chemotherapy in patients with breast cancer

This prospective study was performed to evaluate the effect of systemic chemotherapy on skeletal metastases in breast cancer patients. Serum CA15-3 concentration was determined in 86 metastatic breast cancer patients in bone and correlated to whole skeletal scintigraphy. Fifteen patients with a normal level of CA15-3 [<28 u/ml] were excluded from the study. Also, a control group of 50 breast cancer patients after radical mastectomy with no evidence of local or metastatic deposits were also subjected to bone scintigraphy and serum CA15-3 concentration. Metastatic patients were classified into five groups according to the findings of bone scan from M0 [normal bone scan] to M4 [superscan]. This study suggested that CA15-3 could be a complementary marker in evaluating patients with metastatic breast cancer to bone before and shortly after initiating chemotherapy. It has the advantage of differentiating between disease progression and flare reaction

Evaluation of the efficacy of concurrent cisplatin and radiotherapy in locally advanced head and neck cancer

Thirty-six patients with locally advanced unresectable head and neck squamous cell carcinoma were included in this study. All patients received radiotherapy by cobalt60 machine. They received 70 Gy to the tumor area in 35 fractions for 7 weeks and 50 Gy to the uninvolved cervical and supraclavicular LN in 25 fractions for 5 weeks duration [cisplatin]. Concurrent cisplatin [CDDP] was infused in 3 hours and 1/2 hour before radiotherapy. The dose of CDDP was 20 mg/m2 from day 1 to 5, day 22 to 26 and day 43 to 47. The patients were evaluated for response at three weeks after the completion of irradiation and every month for six months, then every three months. The assessment of the response to treatment showed that the overall response was 75% [61% complete remission [CR] and 14% partial remission [PR]]. Six patients showed a stationary course and three patients showed disease progression. Acute toxicity was tolerable and no treatment interruption occurred. The most frequent toxicity was vomiting GI in 21 patients, stomatitis GII in 17 patients and dryness of the mouth GII in 23 patients. Finally, the results of concurrent radio- and chemotherapy were encouraging and a large number of patients and a long time follow up are needed to assess the improvement in survival

Induction chemotherapy followed by concurrent chemoradiotherapy in the management of locally advanced cancer larynx

This study was performed on 24 patients aiming to determine the efficiency and toxicity of neoadjuvant chemotherapy, followed by concurrent chemoradiotherapy. They received three cycles of platinol, leucovorin and 5-flurouracil, followed by concurrent chemoradiotherapy using cisplatin 20 mg/m2 weekly. After induction therapy only, 2 patients showed a complete clinical response, while 18 patients showed a partial response and 4 remained with progressive disease. After completion of chemoradiotherapy, 85% of the patients showed a complete remission clinically, endoscopically and by histopathological study, while 4 patients showed a partial response and underwent palliative laryngectomy

Early results of pre-irradiation cisplatin and etoposide in the treatment of childhood medulloblastoma

Fifteen children with a pathologically confirmed diagnosis of medulloblastoma were treated with three cycles of cisplatin 100 mg/m2 i.v. Dl and VP16 100 mg/m2 i.v. Dl-3 before standard craniospinal irradiation, then followed by another three cycles chemotherapy after irradiation. After the initial three cycles of cisplatin-VP16, there were three complete responders [CR], nine partial responders [PR], two patients with stationary disease [SD] and one patient had a progressive disease [PD]. After completing the craniospinal irradiation, there were eleven complete responses and four partial responses. At the end of six cycles, there were twelve CRs and three PRs. The progression free survival ranged between 4 and 22 months [mean 14.1 months]. The toxicity of treatment was minimal ranging from mild to moderate nausea for 2-4 days post chemotherapy. Grade 1 neutropenia was encountered in five patients [5 in 90 cycles]. No renal or ototoxicity were encountered during the study