PubMed Health⌕ Search

Biomedical subjects

S E Come

Publications and source records attributed to S E Come.

At least 19 recordsLinked to original sources
PubMed2005

Endocrine treatment options for advanced breast cancer--the role of fulvestrant.

For many years, tamoxifen has been the 'gold standard' amongst anti-oestrogen therapies for breast cancer. However, the selective aromatase inhibitors (AIs), anastrozole, letrozole and exemestane, have demonstrated advantages over tamoxifen as first-line treatments for advanced disease. Anastrozole is also more effective as an adjuvant treatment in early, operable breast cancer and is being increasingly used in the adjuvant setting. Generally, the selective oestrogen receptor modulators (SERMs), such as toremifene, droloxifene, idoxifene, raloxifene, and arzoxifene, show minimal activity in tamoxifen-resistant disease and show no superiority over tamoxifen as first-line treatments. In addition to these agents, other treatment options for advanced disease include high-dose oestrogens and progestins. Response rates for high-dose oestrogens and tamoxifen are similar, but the use of oestrogens is limited by their toxicity profile. Consequently, there is a need for new endocrine treatment options for breast cancer, particularly for use in disease that is resistant to tamoxifen or AIs. Fulvestrant ('Faslodex') is a new type of steroidal oestrogen receptor (ER) antagonist that downregulates cellular levels of the ER and progesterone receptor and has no agonist activity. This paper reviews the key efficacy and tolerability data for fulvestrant in postmenopausal women in the context of other endocrine therapies and explores the potential role of fulvestrant within the sequencing of endocrine therapies for advanced breast cancer.

Anastrozole↗
PubMed1999

Concurrent CMF and radiation therapy for early stage breast cancer: results of a pilot study.

PURPOSE: The optimal sequencing of chemotherapy (CT) and radiotherapy (RT) for patients with early-stage breast cancer treated with breast-conserving therapy is unresolved. Given the concerns arising from delaying either CT or RT, we conducted a pilot study of a concurrent CT-RT regimen in the hope that this would reduce side effects without decreasing efficacy. METHODS AND MATERIALS: From 1992-1994, 112 patients with 0-3 positive nodes received 6 monthly cycles of classic oral chemotherapy with cyclophosphamide, methotrexate, and 5-fluorouracil (5-FU) (CMF). On day 15 of cycle 1, patients started tangential field RT (39.6 Gy in 22 fractions), followed by a 16 Gy boost in 8 fractions. Median follow-up time for surviving patients was 53 months. RESULTS: Moist desquamation developed during or shortly after RT in 50% of patients, but only 5 patients required treatment breaks. Grade 4 neutropenia during RT occurred in 16 patients, but only 1 required hospitalization. One patient developed Grade 2 radiation pneumonitis. Ninety-three percent of patients received at least 85% of prescribed drug doses. Cosmetic scores of 51 evaluable patients approximately 2 years after the end of chemotherapy were 47% excellent, 43% good, and 10% fair. We have observed 4 local failures and 20 distant failures. CONCLUSIONS: This concurrent CT-RT scheme had acceptable toxicity and outcome. Further comparison of this approach allowing prompt initiation of both CT and RT to alternative sequences is warranted.

Adult↗
PubMed1999

Treatment-related toxicity from a randomized trial of the sequencing of doxorubicin and radiation therapy in patients treated for early stage breast cancer.

PURPOSE: There is concern that breast cancer patients treated with left-sided radiation therapy (XRT) and doxorubicin (DOX) may have an increased risk of cardiac toxicity. In addition, the effect of different sequencing of XRT and chemotherapy (CT) on the likelihood of cardiotoxicity, as well as cellulitis, arm edema, or brachial plexopathy, is not well understood. We reviewed the records of patients treated on a randomized trial testing the sequencing of CT and XRT to determine if there was an increase in cardiac events or other complications in patients treated with a total dose of DOX of 180 mg/m2 and XRT, comparing patients with treatment to the left breast and the right breast, and comparing patients treated with initial CT and initial RT. MATERIALS AND METHODS: From June 1984 to December 1992, 244 patients with clinical stage I or II breast cancer were randomized following conservative surgery to receive CT (4 cycles of CAMFP at 3 week intervals) either before or after XRT (45 Gy to the entire breast, followed by a boost of 16 Gy; nodal radiation therapy was optional). Two hundred thirty-one patients were evaluable for the development of cardiac toxicity. The median age at diagnosis was 45 years (range, 20-68). CT doses were: doxorubicin, 45 mg/m2 IV bolus, d 3; methotrexate, 200 mg/m2 IV, d 1 and 15; 5-fluorouracil, 500 mg/m2 IV, d 1; cyclophosphamide, 500 mg/m2 IV, d 1; prednisone 40 mg p.o., d 1-5. A cardiac event was defined as a myocardial infarction or clinical evidence of congestive heart failure. Median follow-up time was 53 months. RESULTS: No cardiac events were observed for patients with either left- or right-sided breast cancer. The sequencing of CT and XRT had no significant effect on the risk of cardiac toxicity, cellulitis, arm edema or brachial plexopathy. CONCLUSIONS: We observed no evidence of an increased risk of cardiac toxicity from the addition of left breast tangential irradiation to DOX at a total dose of 180 mg/m2. Additional follow-up is needed to exclude possible late events. In addition, the sequencing of CT and XRT does not appear to affect the risk of cellulitis, arm edema, or brachial plexopathy.

Adult↗
PubMed1996

The sequencing of chemotherapy and radiation therapy after conservative surgery for early-stage breast cancer.

BACKGROUND: Patients with early-stage breast cancer who are at substantial risk for systemic metastases are increasingly treated with breast-conserving therapy and adjuvant chemotherapy. However, the optimal sequencing of chemotherapy and radiation therapy is not clear. METHODS: Two hundred forty-four patients with stage I or II breast cancer who were at substantial risk for distant metastases were randomly assigned to receive a 12-week course of chemotherapy either before or after radiation therapy. All had had breast-conserving surgery. The median length of follow-up in surviving patients was 58 months (range, 10 to 124). RESULTS: The five-year actuarial rates of cancer recurrence at any site and of distant metastases in the radiotherapy-first group and the chemotherapy-first group were 38 percent and 31 percent (P = 0.17) and 36 percent and 25 percent (P = 0.05), respectively. Overall survival was 73 percent and 81 percent (P = 0.11), respectively. The five-year crude rates of first recurrence according to site in the radiotherapy-first and chemotherapy-first groups, respectively, were 5 percent and 14 percent for local recurrence and 32 percent and 20 percent for distant or regional recurrence or both. This difference in the pattern of recurrence was of borderline statistical significance (P = 0.07). CONCLUSIONS: This study suggests that for patients ar substantial risk for systemic metastases, it is preferable to give a 12-week course of chemotherapy followed by radiation therapy, rather than radiation therapy followed by chemotherapy.

Actuarial Analysis↗
PubMed1994

Sequencing of irradiation and chemotherapy for early-stage breast cancer.

The optimal sequencing and timing of radiation and chemotherapy for patients with early-stage breast cancer are unknown, both with regard to each other and to surgery. Although intuitively it seems prudent to start both radiotherapy and combination chemotherapy as soon as possible following surgery, there is little information to suggest that reasonably short delays (up to a few months, perhaps) are deleterious. Study results do not suggest that concurrent chemoradiotherapy produces any substantial advantage in local control rates, compared with sequential treatment. However, the available data are very limited, and no randomized studies have been performed. Because of its theoretical advantages, concurrent chemoradiotherapy remains an approach worthy of further investigation, but the potential toxicity of such regimens makes careful study design imperative. At present, the effectiveness of chemotherapy does not appear to be impaired significantly by a 2- to 3-month break in therapy imposed by split-course combined-modality regimens.

Breast Neoplasms↗
PubMed1993

Long-term results of post-operative radiation therapy following mastectomy with or without chemotherapy in stage I-III breast cancer.

PURPOSE: To determine the risk of local-regional failure following post-mastectomy radiotherapy and the incidence of complications associated with such treatment. METHODS AND MATERIALS: We retrospectively analyzed the results in 309 patients with Stage I-III invasive breast cancer treated with post-mastectomy radiation therapy between 1975 and 1985. The median radiotherapy dose was 45 Gy in 1.8 to 2.25 Gy fractions. One hundred forty-seven (48%) of the patients received adjuvant systemic chemotherapy with 115 (78%) of these receiving a CMF-based or doxorubicin-containing regimen. The median follow-up time of surviving patients was 130 months (range, 28 to 191 months) after mastectomy. RESULTS: Seventeen patients (6%) developed a local-regional failure at an interval of 4 to 87 months after radiotherapy. Moderate or severe complications related to radiotherapy and requiring treatment were uncommon. Symptomatic radiation pneumonitis occurred in four patients (1.3%), arm edema in 18 (5.8%), and brachial plexopathy in 2 (0.6%). CONCLUSION: We conclude that post-operative radiotherapy is a safe and effective means of reducing local-regional failure following mastectomy. The efficacy of post-mastectomy radiotherapy in improving survival should be addressed in new large randomized controlled studies.

Adult↗
PubMed1991

Cisplatin, continuous-infusion 5-fluorouracil, and intermediate-dose methotrexate in the treatment of unresectable non-small cell carcinoma of the lung.

Forty-one patients with unresectable non-small cell carcinoma of the lung (NSCCL) were treated with cisplatin 20 mg/m2/d for 5 days as a daily bolus injection, 5-fluorouracil 800 mg/m2/d by continuous infusion for 5 days, and intermediate-dose methotrexate 200 mg/m2 on days 15 and 22 of a 28-day cycle (PFM). One complete and 23 partial responses were observed, yielding an overall response rate of 60%. There was no significant difference in response rates based on histologic subtype or extent of disease (locally unresectable versus metastatic). Median duration of response was 6 months, and the median survival of all patients was 10 months. Two patients with unresectable disease at presentation became resectable after chemotherapy and remain disease-free at 46+ and 53+ months. Toxicity was modest, with oral mucositis the major adverse effect. Clinically important neutropenia was uncommon. PFM is an active regimen in NSCCL and deserves further study in the "neoadjuvant" setting.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1991

Integration of conservative surgery, radiotherapy, and chemotherapy for the treatment of early-stage, node-positive breast cancer: sequencing, timing, and outcome.

The optimal means of combining breast-conserving surgery, radiation therapy, and chemotherapy for the treatment of patients with early-stage, node-positive breast cancer is not known. We reviewed the results in 295 patients treated at the Joint Center for Radiation Therapy and affiliated institutions from 1976 to 1985. All patients had positive axillary nodes on dissection, had no gross residual disease in the breast or axilla after surgery, and received breast irradiation (with or without nodal irradiation) and three or more cycles of a cyclophosphamide, methotrexate, and fluorouracil (CMF)-based or doxorubicin-containing regimen. Median follow-up in patients without any failure was 78 months. Breast failure rates were assessed in relation to the sequencing of radiotherapy and chemotherapy. The different sequences were not randomly assigned, and the characteristics of the sequence groups differed. The actuarial 5-year breast failure rate was 4% in 99 patients receiving radiotherapy before chemotherapy; 8% in 54 patients sequentially receiving some chemotherapy, then radiotherapy without concurrent chemotherapy, then further chemotherapy; and 6% in 116 patients receiving concurrent chemotherapy and radiotherapy. However, the failure rate was 41% in 26 patients who received all chemotherapy before radiotherapy. The crude incidences of local failure within 4 years of treatment in these groups were 3%, 2%, 4%, and 15%, respectively (P = .065 for all four groups not being the same). The actuarial 5-year local failure rate was 5% for 252 patients irradiated within 16 weeks after surgery compared with 35% for 34 patients irradiated more than 16 weeks after surgery. The 4-year crude incidences were 4% and 12% for the two groups, respectively (P = .06). These results suggest that delaying the initiation of radiotherapy may result in an increased likelihood of local failure. Formal randomized controlled trials will be needed to confirm these results and to improve the integration of these treatment modalities.

Actuarial Analysis↗
PubMed1990

Elevated creatine kinase and malignancy.

Increased serum levels of CK isoenzymes variously signal heart, brain, or skeletal muscle damage. They may also be markers for advanced tumors with poor prognosis.

Biomarkers, Tumor↗
PubMed1990

Cyclophosphamide, carmustine, and etoposide with autologous bone marrow transplantation in refractory Hodgkin's disease and non-Hodgkin's lymphoma: a dose-finding study.

Cyclophosphamide, carmustine (BCNU), and etoposide (VP-16) (CBV) is a widely used conditioning regimen in autologous bone marrow transplantation (ABMT) of patients with refractory and relapsed lymphoma. However, the maximum-tolerated dose (MTD) of these agents when used in combination has not been systematically explored. We treated 58 patients (28 with non-Hodgkin's lymphoma [NHL], 30 with Hodgkin's disease [HD]) at seven dose levels of CBV. Doses were cyclophosphamide 4,500 to 7,200 mg/m2, BCNU 450 to 600 g/m2, and VP-16 1,200 to 2,000 mg/m2. The MTD was cyclophosphamide 7,200 mg/m2, BCNU 450 mg/m2, and VP-16 2,000 mg/m2. Six hundred milligrams per square meter of BCNU was associated with five of 18 cases of interstitial pneumonitis versus two of 40 at 450 mg/m2 (P = .02). Treatment-related mortality was 5% at dose levels less than or equal to the MTD and 22% at the highest dose. In this heavily pretreated patient population, most of whom had high volume residual disease, complete responses (CRs) to CBV and ABMT occurred in 25% of assessable patients with NHL and 43% of patients with HD. Thirteen of 28 patients with NHL and 14 of 30 with HD remain free from disease progression with median follow-up of 212 and 215 days, respectively. CBV can be administered with acceptable toxicity over a wide range of doses to patients with refractory and relapsed lymphoma.

Adolescent↗
PubMed1989

Use of pulmonary capillary wedge aspirates for the antemortem diagnosis of pulmonary microvascular tumor.

The diagnosis of pulmonary lymphangitic carcinoma usually requires fiberoptic bronchoscopy with transbronchial biopsy, percutaneous needle aspiration of the lung, and/or open lung biopsy. We performed right heart catheterization in three patients with adenocarcinoma, in whom the diagnosis of pulmonary lymphangitic carcinoma was made on the basis of cytologic examination of pulmonary capillary blood.

Adenocarcinoma↗
PubMed1985

Stage III Hodgkin's disease: improved survival with combined modality therapy as compared with radiation therapy alone.

This is a retrospective analysis of 120 patients with pathologically stage IIIA and IIIB Hodgkin's disease treated from April 1969 to December 1982. The median follow-up was 108 months. Treatment consisted of radiation therapy (RT) alone in 54 patients and combined radiation therapy and MOPP (nitrogen mustard, vincristine, procarbazine, prednisone) chemotherapy (CMT) in 66 patients. Stage III patients treated with CMT have an improved actuarial 12-year survival as compared with patients treated with RT alone with MOPP reserved for relapse (80% v 64%; P = .026). The 12-year actuarial freedom from first relapse by treatment for stage III patients is 83% and 40%, respectively (P less than .0001). Improved survivals following combined modality therapy are seen for the following subgroups of stage III patients: stage III2, 66% (CMT) v 44% (total nodal irradiation; TNI), P = .04; stage III1, 97% (CMT) v 73% (TNI), P = .05; stage III mixed cellularity or lymphocyte depletion histology, 94% (CMT) v 65% (TNI), P = .007; and stage III extensive splenic involvement, 77% (CMT) v 58% (TNI), P = .02. These survival differences are not seen in patients with nodular sclerosis or lymphocyte predominance histology or in patients with minimal splenic involvement. These data indicate that the initial use of CMT in stage III Hodgkin's disease results in an improved survival as compared with initial treatment with RT with MOPP reserved for relapse. Patients with limited Stage IIIA disease may still be candidates for radiation therapy alone.

Actuarial Analysis↗
PubMed1984

Pulmonary uptake of technetium 99m macroaggregated albumin: a predictor of gastrointestinal toxicity during hepatic artery perfusion.

Hepatic artery infusion of 5-fluoro-2-deoxyuridine (5-FUdR) provides high hepatic drug levels but little systemic toxicity, since, by this route of administration, the drug is detoxified by the hepatocytes. Slow infusion of technetium 99m- (99mTc) labeled macroaggregated albumin (MAA) through the hepatic artery is an aid in catheter placement, in predicting response of liver metastases to therapy, and in identifying extra-hepatic flow in the gastroduodenal or splenic arteries as an indicator of systemic toxicity. Marked pulmonary uptake of this tracer after slow radionuclide hepatic angiography was noted in four patients who showed major gastrointestinal (GI) toxicity. A retrospective examination of pulmonary accumulation of 99mTcMAA as a predictor of GI toxicity is the subject of this paper. Two groups of patients were evaluated. The first group consisted of 14 consecutive patients in whom continuous infusion of drug was administered by an external pump by way of a percutaneous catheter. Patients received baseline and follow-up (seven to 27 days) slow-infusion tracer studies (2 to 4 mCi 99mTcMAA at 10 to 21 mL/h). The second group included 14 consecutive patients who were receiving intraarterial chemotherapy by a totally implantable pump system. All received baseline slow-infusion studies (2 to 4 mCi 99mTcMAA at approximately 0.5 to 1.0 mL/min). The percentage of the injected dose in the lung was determined. Patients with greater than 20% of tracer in the lung after radionuclide hepatic angiography had significantly greater severe GI toxicity than patients with baseline values of less than 20%. Our findings support the existence of hepatic arteriovenous (A-V) communications in some patients and suggest that they are present pretherapy. Presence of these A-V communications, which can result in a vascular bypass of normal hepatic parenchyma and the subsequent decrease in hepatic detoxification of chemotherapeutic agents, is the likely cause of GI toxicity. Pulmonary uptake of tracer injected in the hepatic artery may be useful in quantifying the degree of shunting and facilitate the monitoring of potential systemic toxicity.

Antineoplastic Agents↗
PubMed1981

Therapeutic embolization of the gastroduodenal artery in hepatic artery infusion chemotherapy.

Transcatheter embolization of the gastroduodenal artery with Gelfoam was performed in 12 patients undergoing percutaneous hepatic artery catheterization for infusion chemotherapy of metastatic liver disease. The purpose of the embolization was to prevent chemotherapeutic drugs from reaching the stomach and duodenum and thereby inducing gastrointestinal toxicity in patients in whom the catheter tip could not be satisfactorily positioned beyond the gastroduodenal origin. Embolization proved safe and effective in eight cases. Three other patients experienced clinical problems that may or may not have been related to embolization. The final patient had a significant complication (necrosis of the pancreatic head and gastric mucosa) that was felt to be directly related to the embolization. Transcatheter gastroduodenal occlusion may help reduce gastrointestinal toxicity of intraarterial infusion chemotherapy. However, it may on occasion be associated with significant complications, particularly in patients who are debilitated due to metastatic disease.

Adult↗