Improved combination chemotherapy in advanced gastric cancer.

Thirty-five patients with advanced-stage metastatic or unresectable gastric adenocarcinoma were given combination chemotherapy consisting of fluorouracil, doxorubicin, and 1,3-bis (2-chlorbethyl)-1-nitrosourea. Two patients achieved complete remission and 16 partial remission to give an overall response rate of 52%. Six further patients (17%) had stable disease, while in 11 (31%) the disease showed clear-cut progression despite treatment. The only pretreatment factors that suggested poor prognosis were poor initial patient performance and the stomach as the predominant site of disease. Patients responding to treatment had a significantly longer time to relapse (median 48 weeks) than patients with stable disease (median 16 weeks) and a significantly improved survival time (medians, 52 weeks with 30% of patients'' living at 88 weeks and 32 weeks with all dead at 64 weeks respectively). Comparing these results with those in other reports indicated that the three-drug combination chemotherapy consisting of fluorouracil, doxorubicin, and either a nitrosourea or mitomycin was superior to single and two-drug regimens and currently represents the optimum treatment for advanced-stage gastric cancer. Gastric adenocarcinoma should now be considered to be a gastrointestinal malignancy that is relatively susceptible to chemotherapy, and studies of these improved chemotherapeutic regimens as post-surgical adjuvants may lead to further improvements in prognosis.     

Treatment with sorafenib in advanced thyroid cancer - a case report

Papillary thyroid cancer (PTC) usually has a good prognosis. The treatment, including total thyroidectomy and complementary radioiodine (RAI) therapy, gives complete remission in 90% of patients. However, in 10% of subjects with metastatic disease, the prognosis is poor. In the group of patients with disease progression and no 131I uptake, searching for new therapeutic modalities before all tyrosine kinase inhibitors and other antiangiogenic agents is necessary. The study presents the case of a 55-year-old male with advanced PTC /pT3mNxMo/ diagnosed in 1993. Primary treatment by total thyroidectomy and 131I ablation led to complete remission. In 2000 local as well as lymph node recurrence was diagnosed and successively treated by surgery. In 2006 an increasing serum thyroglobulin level was noted and a single lung metastasis was diagnosed and operated on. In 2007 new foci in CNS and vertebral column with no 131I uptake were stated. Further progression (bones, CNS, and pterygoid muscle) was confirmed by PET-CT. The patient underwent neurosurgical metastasectomy twice and palliative CNS and vertebra's radiotherapy. Liver metastases were diagnosed in 2009. Treatment with increasing doses of thalidomide (up to 800 mg/d) was administered for 3 months with a good tolerance; however, the therapy was withdrawn due to cancer progression. Next, sorafenib (800 mg/d) was given for 16 weeks. Radiological examination performed after 16 weeks confirmed stable disease, whereas 2 months later, after sorafenib withdrawal due to lack of treatment possibility, further progression was observed. Metronomic chemotherapy with Adriamycin was instituted which gave disease stabilization for 6 months. The patient died with advanced disseminated disease due to pulmonary embolism. We present this case to document no adverse effects of therapy with sorafenib in a patient with brain DTC metastases. Sorafenib therapy was only short-term, but no progression occurred in this time.     

Complex treatment of inflammatory breast cancer

Inflammatory breast cancer represents 2-5% of all malignant breast lesions. Its rapid progression, the rather short medical history of the disease is unique and seems to be very typical. The combined modality treatment of inflammatory breast cancer is a special challenge for the medical oncologists. Preoperative chemotherapy is of great importance. After getting fair remission, surgery and radiotherapy should be delivered. With combined modality therapy the 5-year overall survival is about 50%. Knowing more pharmaco-genomic details on the disease and delivering new medicaments the effectiveness of the treatment will be further enhanced.     

Long-Term Treatment After Preoperative High-Dose Chemotherapy in a Lactating Breast Cancer Patient

Breast cancer during lactation is very rare, accounting for <3 % of all breast cancers. Its diagnosis and treatment is often delayed during pregnancy. We report a case of female lactating breast carcinoma in a 29-year old patient. The disease was stage IIIB (T4N1M0). The patient received preoperative induction chemotherapy and high-dose chemotherapy with peripheral blood stem cell support, followed by adjuvant chemotherapy and endocrine therapy. The metastases were detected 17 months after operation, palliative treatment including different chemotherapy for 60 cycles, locoregional radiotherapy and endocrine therapy. The total number of cycles of chemotherapy was 67, and the survival time was 118 months. We discuss the diagnosis and treatment options for breast cancer during lactation, based on a literature review.     

Treatment of stage I seminoma: is it time to change your practice?

Hepatocellular carcinoma is rare, but increasing in prevalence in the United States. Recent studies have shown that sorafenib, a multikinase inhibitor, can reduce tumor progression in patients with this cancer. However, complete remission has not been observed. We report a case of a 78-year old patient with unresectable metastatic hepatocellular carcinoma who had a rapid and complete clinical response following therapy with sorafenib for six months. No evidence of disease recurrence has been noted for 6 months after discontinuation of therapy.     

Clinical Efficacy of Including Capecitabine in Neoadjuvant Chemotherapy for Breast Cancer: A Systematic Review and Meta-Analysis of Randomized Controlled Trials

Background

Capecitabine has proven effective as a chemotherapy for metastatic breast cancer. Though several Phase II/III studies of capecitabine as neoadjuvant chemotherapy have been conducted, the results still remain inconsistent. Therefore, we performed a meta-analysis to obtain more precise understanding of the role of capecitabine in neoadjuvant chemotherapy for breast cancer patients.

Methods

The electronic database PubMed and online abstracts from ASCO and SABCS were searched to identify randomized clinical trials comparing neoadjuvant chemotherapy with or without capecitabine in early/operable breast cancer patients without distant metastasis. Risk ratios were used to estimate the association between capecitabine in neoadjuvant chemotherapy and various efficacy outcomes. Fixed- or random-effect models were adopted to pool data in RevMan 5.1.

Results

Five studies were included in the meta-analysis. Neoadjuvant use of capecitabine with anthracycline and/or taxane based therapy was not associated with significant improvement in clinical outcomes including: pathologic complete response in breast (pCR; RR = 1.10, 95% CI 0.87–1.40, p = 0.43), pCR in breast tumor and nodes (tnpCR RR = 0.99, 95% CI 0.83–1.18, p = 0.90), overall response rate (ORR; RR = 1.00, 95% CI 0.94–1.07, p = 0.93), or breast-conserving surgery (BCS; RR = 0.98, 95% CI 0.93–1.04, p = 0.49).

Conclusions

Neoadjuvant treatment of breast cancer involving capecitabine did not significantly improve pCR, tnpCR, BCS or ORR. Thus adding capecitabine to neoadjuvant chemotherapy regimes is unlikely to improve outcomes in breast cancer patients without distant metastasis. Further research is required to establish the condition that capecitabine may be useful in breast cancer neoadjuvant chemotherapy.     

Retrospective Analysis of 234 Nasopharyngeal Carcinoma Patients with Distant Metastasis at Initial Diagnosis: Therapeutic Approaches and Prognostic Factors

Purpose

The purpose of this retrospective study was to identify the independent prognostic factors and optimize the treatment for nasopharyngeal carcinoma (NPC) patients with distant metastasis at initial diagnosis.

Methods

A total of 234 patients referred between January 2001 and December 2010 were retrospectively analyzed. Among the 234 patients, 94 patients received chemotherapy alone (CT), and 140 patients received chemoradiotherapy (CRT). Clinical features, laboratory parameters and treatment modality were examined with univariate and multivariate analyses.

Results

The median overall survival (OS) time was 22 months (range, 2-125 months), and the 1-year, 2-year, 3-year overall survival rates were 82.2%, 51.3% and 34.1%. The overall response and disease control rates of metastatic lesions after chemotherapy were 56.0% and 89.8%. The factors associated with poor response were karnofsky performance score (KPS) <80, liver metastasis, lactate dehydrogenase (LDH)>245 IU/L, and number of chemotherapy cycles <4. The 3-year OS of patients receiving CRT was higher than those receiving CT alone (48.2% vs. 12.4%, p<0.001). Subgroup analysis showed that significantly improved survival was also achieved by radiotherapy of the primary tumor in patients who achieved complete remission (CR)/partial remission (PR) or stable disease (SD) of metastatic lesions after chemotherapy. Significant independent prognostic factors of OS were KPS, liver metastasis, levels of LDH, and multiple metastases. Treatment modality, response to chemotherapy and chemotherapy cycles were also associated with OS.

Conclusion

A combination of radiotherapy and chemotherapy seems to have survival benefits for selected patients with distant metastases at initial diagnosis. Clinical and laboratory characteristics can help to guide treatment selection. Prospective randomized studies are needed to confirm the result.     

5-FLUOROURACIL IN METASTATIC MAMMARY CANCER

Thirty patients with advanced metastatic breast cancer were treated with 5-fluorouracil. There were two deaths attributable to drug toxicity. Ten additional patients died of advancing disease, and of this group only two showed significant remissions as a result of drug therapy. Of the 18 patients surviving, 17 obtained objective and subjective remission from their disease and 12 were in complete remission from four to fourteen months from institution of therapy. In four of these cases, radiation therapy was combined with chemotherapy.     

药物联合新辅助化疗(ET)对三阴乳腺癌患者生存状态的改善及其疗效评价

目的:观察表柔比星和多西紫杉醇联合新辅助化疗(ET)对三阴乳腺癌患者生存状态的改善及其疗效,评价该化疗方案在三阴乳腺癌的化疗中加入紫杉类化疗药物的可行性。方法:收集我院2011年1月至2011年12月收治的300例乳腺癌患者,将患者随机分为两组,研究组及对照组,每组各150例。对照组采用单纯表柔比星,研究组采用新辅助化疗的方案(ET方案),随访12个月,统计两组临床疗效并进行评价。结果:研究组完全缓解率(92.00%)明显高于对照组的78.00%,疾病无缓解率(1.33%)及疾病恶化率(0%)明显低于对照组的14.00%及1.33%,差异具有统计学意义(P0.01)。随访期间,对照组患者68例(45.3%)复发或转移,而研究组患者35例(23.3%)出现复发或远处转移,两者比较,差异显著(P0.001)。结论:在三阴乳腺癌的化疗中加入紫杉类化疗药物是可行的,效果显著。     

Everolimus and exemestane in long survival hormone receptor positive male breast cancer: case report

Background

Male breast cancer is a rare event, accounting for approximately 1% of all breast carcinomas. Although men with breast cancer had poorer survival when compared with women, data on prognosis principally derive from retrospective studies and from extrapolation of female breast cancer series. We reported the case of a very long survival patient.

Case presentation

A caucasian 42-year-old man underwent radical mastectomy with axillary dissection for breast cancer in 1993. Pathologic stage was pT4pN0M0 infiltrating ductal carcinoma of right breast without lymph nodes metastases. Biological characterization was not available. He received adjuvant treatment with chemotherapy, six cycles of cyclophosphamide, methotrexate and fluorouracil, then endocrine therapy with tamoxifen for 5 years and complementary radiotherapy. Then he began clinical-instrumental follow up. In May 1996, a computed tomography scan showed multiple lung metastases. Hereafter he received several oncologic treatment including seven chemotherapy and five endocrine therapy lines with two re-challenge of endocrine therapy. In October 2007 further lung progression was showed and a biopsy was performed to characterize the disease. Histological examination confirmed breast cancer metastases, immunohistochemistry showed positive staining for estrogen receptor, negative for progesterone receptor and human epithelial growth factor receptor 2, proliferative index was 21%. In April 2013, bone disease progression was evident and he received radiant treatment to sacral spine. In May 2014 an off-label treatment with exemestane and everolimus combination was approved by Ethics Committee of the Marche Region. The patient received treatment for 3 months with evident clinical benefit to subcutaneous lesions of the chest wall that were not visible nor palpable on physical examination after 1 month of treatment.

Conclusion

That is the case of long survival male breast cancer patient with luminal B subtype and no BRCA mutations. He achieved higher progression free survival with endocrine therapy creating the rationale for last line treatment with everolimus and exemestane combination. Attending conclusive results from ongoing studies, everolimus and exemestane should not be used routinely in male metastatic breast cancer patients, but taking into account for selected cases. At the best of our knowledge, this is the first case of male beast cancer treated with exemestane and everolimus combination.

     

Doxorubicin and paclitaxel vs. 5-fluorouracyl,doxorubicin and cyclophosphamid in the first line treatment of metastatic breast cancer

Combined chemotherapy of breast cancer using antracyclins proved to be superior over classical drug combinations. Taxanes are considered even more effective agents against breast cancer than the previously used drugs. Based on these assumptions, multicentric phase III trial was initiated in Europe to compare the AT combination (doxorubicin and paclitaxel) with the classical FAC (5-fluorouracyl, doxorubicin and cyclophosphamid). AT combination proved to be more effective in the treatment of metastatic breast cancer than FAC as far as the overall response rate and the complete responses are concerned. Furthermore, the time to progression increased in the AT-arm too compared to the FAC-arm. Based on these data it is suggested to use AT combination for the first-line treatment of metastatic breast cancer.     

Central nervous system metastasis from osteosarcoma: Case report and literature review

Osteosarcoma is the most common primary malignancy of bone in children and young adults, the highest incidence peak is during adolescence and doesn’t have any gender predominance. The main site of metastasis are the lungs and extrapulmonary cases are occasional. The incidence of metastasis in the Central Nervous System (CNS) is 2–6.5%, increase to 10–15% in patients with pulmonary metastases. Therefore, metastatic disease of the CNS is rare and the information on such patients is limited. Here, we describe a case of a 20-year old patient diagnosed with osteosarcoma in the left distal femur stage IIB, he developed pulmonary disease, during palliative chemotherapy experienced relapse to the brain classified as recursive partitioning analysis (RPA) class II, and was treated with external radiotherapy (30?Gy in 10 fractions) and later he had a poor evolution and died.     

TPS monitoring in metastatic breast cancer.

The management of metastatic breast cancer patients reflects the heterogeneous nature of the disease. While patients may benefit from hormonal treatment, in most cases more toxic chemotherapy is applied in the advanced stages. The pretreatment levels of TPS in patients with metastatic breast cancer are correlated with prognosis. Decreasing TPS levels (> 50%) during treatment are indicative of response. The fastest decrease in TPS levels is obtained in patients with a favorable prognosis. Increasing TPS levels (> 25%) predict disease progression with a considerable lead time (median 8 months). The clinical impact of these observations is discussed in this paper.     

Long term remission of metastatic placental site trophoblastic tumor (PSTT): Case report and review of literature

BACKGROUND: Placental site trophoblastic tumor (PSTT) is a rare and unique form of gestational trophoblastic disease (GTD). This tumor represents a neoplastic transformation of intermediate trophoblastic cells. We document a case of long term remission in a patient with metastatic PSTT. CASE PRESENTAION: A 27-year-old patient with metastatic PSTT was treated with combination therapy (chemotherapy and surgery). Patient is alive after 10 years without any evidence of recurrence. Literature on PSTT was searched using Medline and cross references, and pertinent articles were reviewed. CONCLUSION: With surgery and chemotherapy it is possible to achieve long-term remission in metastatic PSTT. Only a handful of previously reported cases with prolonged remission had been treated with the described combined chemotherapy and surgical approach. We suggest that this approach may be recommended for metastatic PSTT.     

Role of Iphosphamide in the treatment of breast cancer

Breast cancer is the most frequent solid tumor in women. Predictive and prognostic factors play an important role in the treatment of this cancer. We focused on high risk and heavily pre-treated metastatic breast cancer patients, trying to find the best combination of cytotoxic drugs with high efficacy and low toxicity. Ifosfamide is chemically related to nitrogen mustard and is a synthetic analogue of cyclophosphamide. Ifosfamide has a wide range of antitumor activity. Since ifosfamide as monotherapy has introduced significant tumor reduction in 1(st) line chemotherapy for advanced breast cancer, some studies started with high-dose continuous infusion of ifosfamide,or combined with paclitaxel or vinorelbine. Patients with poor prognosis primary breast cancer treated with high-dose chemotherapy supported by peripheral blood progenitor cell (PBSC) transplantation have lower risk for local relapse and longer disease-free-survival. Ifosfamide working in the mobilization regimen has effective anti-tumor activity while mobilizing sufficient PBPCs in the majority of patients. In combination with other cytotoxics showed to be effective in high-dose protocols.     

Dose-intensive chemotherapy with stem cell support as a treatment strategy for bone and soft-tissue sarcomas

Whether high-dose chemotherapy with stem cell support improves the long-term outcome for patients with bone and soft-tissue sarcoma is debatable and controversial. Prognosis of patients with unresectable or advanced metastatic sarcoma remains poor with a disease-free survival at 5 years less than 10%; treatment is generally considered to be palliative. Doxorubicin, epirubicin and ifosfamide are the most active single agents with response rates above 20%. Although drug combinations result in higher response rates, superiority against single agent chemotherapy in terms of survival could not have been demonstrated yet. As a dose-response relationship has been shown for the anthracyclines and especially for ifosfamide, high-dose chemotherapy with stem cell support has been evaluated by several investigators. However, all studies were not randomized, comprised small patient numbers and included heterogeneous histological subtypes of soft-tissue sarcomas. Nevertheless, higher doses of chemotherapy result in higher remission rates, which could correlate with longer survival. Well-designed randomized trials should be performed. In this review article, we overview the literature and on the basis of our own data we emphasize the value of high-dose chemotherapy as a treatment option for younger patients with a good performance status in complete or partial remission prior to high-dose chemotherapy.     

Cancer du sein métastatique : progrès dans la prise en charge et limites actuelles

Breast cancer remains a major public health problem. Even if there is an increase of this cancer curability, mainly related to the advances in screening and adjuvant therapies, metastatic breast cancer remains a lethal disease in the vast majority of cases. Therapeutic advances in the chemotherapy and targeted therapies fields induced an increase in survival, however the proportion of long survivors remains low. One of the putative hypotheses of these results can be in the phenotypic instability of cancer cells, an early process initiated during tumour progression, and metastatic stage of the disease. An increasing amount of scientific data are pledging for a reanalysis of the phenotypic profile of metastatic lesions in order to identify drugable targets and allow individualisation of the treatment of theses metastatic breast cancer patients. This article presents a comprehensive analysis of the frequency of theses phenotypic changes altogether with new modalities to evaluate this phenotypic status.     

Systems Biology and Genomics of Breast Cancer

It is now accepted that breast cancer is not a single disease, but instead it is composed of a spectrum of tumor subtypes with distinct cellular origins, somatic changes, and etiologies. Gene expression profiling using DNA microarrays has contributed significantly to our understanding of the molecular heterogeneity of breast tumor formation, progression, and recurrence. For example, at least two clinical diagnostic assays exist (i.e., OncotypeDX RS and Mammaprint®) that are able to predict outcome in patients using patterns of gene expression and predetermined mathematical algorithms. In addition, a new molecular taxonomy based upon the inherent, or “intrinsic,” biology of breast tumors has been developed; this taxonomy is called the “intrinsic subtypes of breast cancer,” which now identifies five distinct tumor types and a normal breast-like group. Importantly, the intrinsic subtypes of breast cancer predict patient relapse, overall survival, and response to endocrine and chemotherapy regimens. Thus, most of the clinical behavior of a breast tumor is already written in its subtype profile. Here, we describe the discovery and basic biology of the intrinsic subtypes of breast cancer, and detail how this interacts with underlying genetic alternations, response to therapy, and the metastatic process.     

Radiation induced esophageal adenocarcinoma in a woman previously treated for breast cancer and renal cell carcinoma

ABSTRACT: BACKGROUND: Secondary radiation-induced cancers are rare but well-documented as long-term side effects of radiation in large populations of breast cancer survivors. Multiple neoplasms are rare. We report a case of esophageal adenocarcinoma in a patient treated previously for breast cancer and clear cell carcinoma of the kidney CASE PRESENTATION: A 56 year-old non smoking woman, with no alcohol intake and no familial history of cancer; followed in the National Institute of Oncology of Rabat Morocco since 1999 for breast carcinoma, presented on consultation on January 2011 with dysphagia. Breast cancer was treated with modified radical mastectomy, 6 courses of chemotherapy based on CMF regimen and radiotherapy to breast, inner mammary chain and to pelvis as castration. Less than a year later, a renal right mass was discovered incidentally. Enlarged nephrectomy realized and showed renal cell carcinoma. A local and metastatic breast cancer recurrence occurred in 2007. Patient had 2 lines of chemotherapy and 2 lines of hormonotherapy with Letrozole and Tamoxifen assuring a stable disease. On January 2011, the patient presented dysphagia. Oesogastric endoscopy showed middle esophagus stenosing mass. Biopsy revealed adenocarcinoma. No evidence of metastasis was noticed on computed tomography and breast disease was controlled. Palliative brachytherapy to esophagus was delivered. Patient presented dysphagia due to progressive disease 4 months later. Jejunostomy was proposed but the patient refused any treatment. She died on July 2011 CONCLUSION: we present here a multiple neoplasm in a patient with no known family history of cancers. Esophageal carcinoma is most likely induced by radiation. However the presence of a third malignancy suggests the presence of genetic disorders.     

Breast cancer local recurrence under the form of inflammatory carcinoma,treated with concurrent radiation and chemotherapy,a case report

The authors present a case report of a patient with breast cancer diagnosed in 2005, treated with conservative surgery, adjuvant chemotherapy and radiotherapy, followed by hormonal therapy until 2010, who relapsed under the form of inflammatory breast cancer in 2011. After tumor progression detected during primary systemic therapy, a concurrent radiation and radiosensitizing chemotherapy were proposed. There was a significant clinical response to this treatment, enabling curative chance with total mastectomy. The histological examination of the breast and regional lymph nodes revealed a complete response, since there was no evidence of residual tumor.There are few reports concerning concurrent radiotherapy and chemotherapy in locally advanced breast cancer, but it could be a suitable “loco regional rescue therapy” to further reduce tumor progression and allow curative surgery. Study of this treatment strategy in randomized clinical trials is warranted.