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Biomedical subjects

M V Seiden

Publications and source records attributed to M V Seiden.

At least 19 recordsLinked to original sources
PubMed2003

Paclitaxel resistance: molecular mechanisms and pharmacologic manipulation.

It has been approximately ten years since the Food and Drug Administration (FDA) approved paclitaxel for the treatment of platinum resistant epithelial ovarian carcinoma. Since the approval, the drug has found therapeutic applications in a variety of schedules and in a wide variety of epithelial malignancies. Its novel mechanism of action provided the hope that it would demonstrate anti-neoplastic activity in multidrug resistant tumor cells. Unfortunately, as with other chemotherapeutic drugs, resistance is commonly seen. Laboratory investigation has defined a wide variety of resistance mechanisms including overexpression of multidrug resistance (MDR-1) gene, molecular changes in the target molecule (betatubulin), changes in apoptotic regulatory and mitosis checkpoint proteins, and more recently changes in lipid composition and potentially the overexpression of interleukin 6 (IL-6). This review describes the in vitro molecular data that define and support the various mechanisms of resistance and critically evaluates the evidence for the participation of these mechanisms in clinically relevant paclitaxel resistance. This review also explores pharmacologic attempts to modulate paclitaxel resistance, principally through inhibition of the MDR-1 drug efflux pump. Future avenues for drug resistance research and its pharmacologic manipulation in the clinic are discussed.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed2002

Phase I trial of intraperitoneal injection of the E1B-55-kd-gene-deleted adenovirus ONYX-015 (dl1520) given on days 1 through 5 every 3 weeks in patients with recurrent/refractory epithelial ovarian cancer.

PURPOSE: Resistance to chemotherapy in ovarian cancer is frequently associated with mutations in the p53 gene. The adenovirus dl1520 (ONYX-015) with the E1B 55-kd gene deleted, allowing selective replication in and lysis of p53-deficient tumor cells, has shown preclinical efficacy against p53-deficient nude mouse-human ovarian carcinomatosis xenografts. PATIENTS AND METHODS: We undertook a phase I trial of intraperitoneal dl1520 in patients with recurrent ovarian cancer. Sixteen women with recurrent/refractory ovarian cancer received 35 cycles (median, two cycles) of dl1520 delivered on days 1 through 5 in four dose cohorts: 1 x 10(9) plaque forming units (pfu), 1 x 10(10) pfu, 3 x 10(10) pfu, and 1 x 10(11) pfu. RESULTS: The most common significant toxicities related to virus administration were flu-like symptoms, emesis, and abdominal pain. One patient receiving 1 x 10(10) pfu developed common toxicity criteria grade 3 abdominal pain and diarrhea, which was dose-limiting. The maximum-tolerated dose was not reached at 10(11) pfu, and at this dose level patients did not experience significant toxicity. There was no clear-cut evidence of clinical or radiologic response in any patient. Blood samples were taken for adenovirus DNA and neutralizing antibodies. Polymerase chain reaction data indicating presence of virus up to 10 days after the final (day 5) infusion of dl1520 are suggestive of continuing viral replication. CONCLUSION: This article therefore describes the first clinical experience with the intraperitoneal delivery of any replication-competent/-selective virus in cancer patients.

Adenoviridae↗
PubMed2002

Overexpression of IL-6 but not IL-8 increases paclitaxel resistance of U-2OS human osteosarcoma cells.

The cytokines IL-6, initially recognized as a regulator of immune and inflammatory response and IL-8, a potential regulator of angiogenesis, also regulate the growth of many tumor cells. Human cancer cells selected for multidrug resistance to common chemotherapeutic agents demonstrate increased expression of IL-6 and IL-8. To determine whether IL-6 or IL-8 overexpression contributes directly to the drug resistant phenotype, IL-6 or IL-8 cDNA were introduced into the paclitaxel sensitive human osteosarcoma cell line U-2OS using the pIRESneo bicistronic expression vector. Interleukin-6 and IL-8 transfectants were selected for either high IL-6 or IL-8 secretion and evaluated in drug resistance assays. Two IL-6 and two IL-8 secreting clones express IL-6 or IL-8 levels of 10 ng/ml and 1 ng/ml in culture, while parental U-2OS and pIRESneo vector transfected control cells express IL-6 and IL-8 levels of 0.005 ng/ml and 0.1 ng/ml, respectively. MTT cytotoxicity with IL-6 transfected cells demonstrates a five-fold increase in resistance to paclitaxel and a four-fold increase in resistance to doxorubicin as compared to U-2OS. There are no changes in mitoxantrone or topotecan resistance in the IL-6 transfectants as compared to parental U-2OS. Northern analysis of IL-6 transfectants demonstrates that the resistant phenotype is not related to increased levels of MDR-1, MRP-1, or LRP. Western analysis also confirms that P-glycoprotein levels are not altered in IL-6 transfectants. Further supporting an MDR-1 independent mechanism of drug resistance, verapamil cannot reverse paclitaxel resistance in transfected cells, findings further supported by rhodamine 123 exclusion data. Treatment of IL-6 transfected cells with paclitaxel, compared with drug-sensitive parental U-2OS, shows U-2OS(IL-6) are significantly more resistant to apoptosis induced by paclitaxel and exhibit decreased proteolytic activation of caspase-3. In contrast U-2OS(IL-8) transfectants demonstrate no appreciable increase in paclitaxel resistance when compared with parental cells. In summary, while both IL-6 and IL-8 are overexpressed in paclitaxel resistant cell lines, only IL-6 has the potential to contribute directly to paclitaxel and doxorubicin resistance in U-2OS. This resistance is through a non-MDR-1 pathway.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed2001

A Phase I-II study of 96-hour infusional topotecan and paclitaxel for patients with recurrent Müllerian tumors.

BACKGROUND: Topotecan and paclitaxel are schedule dependent chemotherapeutic agents with activity against ovarian carcinoma. A Phase I-II study in which both drugs were administered concurrently by 96-hour, continuous, intravenous infusion was performed to determine the maximum tolerated dose (MTD), toxicities, pharmacokinetics, and efficacy of the combination. METHODS: Women with ovarian or primary peritoneal carcinoma and documented recurrent disease were eligible for the study. The dose of topotecan was escalated from 1.6 mg/m(2) while maintaining the paclitaxel dose constant at 100 mg/m(2). Plasma concentrations of both drugs were monitored daily during the first cycle of therapy. RESULTS: Forty-five patients with a median age of 54 years (range, 42-70 years) received 181 cycles of therapy. Five patients were recruited to each of four dose levels (topotecan 1.6 mg/m(2), 2.0 mg/m(2), 2.8 mg/m(2), and 3.6 mg/m(2)), and an additional 25 patients were treated at the MTD (Phase II). Neutropenia and thrombocytopenia became dose limiting toxicities (DLT) at the fourth dose level. Emesis, mucositis, peripheral neuropathy, diarrhea, and alopecia were mild. Twenty patients (44%) had line-related occlusion, thrombosis, or infection. The mean values (+/- standard deviation) of the apparent steady-state plasma concentrations at the Phase II doses were 2.3 nM +/- 0.5 nM for topotecan lactone, 5.6 nM +/- 2.1 nM for total topotecan, and 40.1 nM +/- 16.8 nM for paclitaxel. There were seven partial responses (Phase II) contributing to an objective response rate of 28% and a median survival time of 11.7 months (range, 0.6-20.1 months). CONCLUSIONS: Topotecan at a dose of 2.8 mg/m(2) and paclitaxel at a dose of 100 mg/m(2) administered by concurrent, 96-hour, continuous intravenous infusions shows activity against tumors of Müllerian origin.

Adult↗
PubMed2001

The clinical utility of liposomal doxorubicin in recurrent ovarian cancer.

OBJECTIVES: The aim of this study was to determine the efficacy and toxicity of single agent off-protocol, liposomal doxorubicin (Doxil Alza), in consecutive patients with recurrent ovarian cancer and to investigate the influence of HER-2/neu expression on response to liposomal doxorubicin. PATIENTS AND METHODS: Retrospective analysis of 72 consecutive patients treated, typically with liposomal doxorubicin 40 mg/m(2) q28 days between January 1997 and December 1998. Results. Twenty-nine patients (40%) had platinum- and taxane-resistant tumors. Nineteen patients (27%) responded with clinical or radiological evidence of response with reduction in CA-125 of >50%. One complete response (CR) and 7 partial responses (PRs) occurred in platinum- and taxane-resistant patients (radiological response (RR) 29%) and 8 PRs occurred in patients with visceral metastases (RR 28%). Time to progression was 5.3 (2.1-12.1) months. Only 7 dose delays (3%) and 20 dose reductions (8%) were necessary in 265 cycles of treatment. Hematological toxicity was generally mild with grade (Gr) > or =III neutropenia in 1 (2%), Gr > or =III thrombocytopenia in 1 (1%), and Gr > or =III anemia in 8 patients (11%). One patient (1%) was admitted with fever and neutropenia. Other toxicity was minimal with Gr > or =III mucositis occurring in 3 patients (4%). Gr > or =III cutaneous toxicity was seen in 6 patients (8%). Three patients (4%) had a >10% fall in ejection fraction but there was no unequivocal clinical heart failure. CONCLUSIONS: The data suggest that liposomal doxorubicin is an active drug in both taxane- and platinum-sensitive and resistant recurrent ovarian cancer. Liposomal doxorubicin is associated with tolerable toxicity and is particularly well tolerated in patients with multiple prior lines of treatment.

Adult↗
PubMed2001

Successful pregnancy after high-dose cyclophosphamide, carboplatinum, and taxol with peripheral blood stem cell transplant in a young woman with ovarian carcinoma.

BACKGROUND: Both ovarian carcinoma and high-dose chemotherapy tend to preclude future pregnancies. CASE: We report a case of a young woman with borderline ovarian carcinoma and invasive tumor implants who underwent surgical debulking with preservation of future fertility followed by carboplatinum, paclitaxel (Taxol), and subsequent high-dose chemotherapy with subsequent peripheral blood stem cell rescue as part of a phase I clinical trial. After a brief period of amenorrhea, the patient had a successful pregnancy that was complicated by a spontaneous abortion in the first trimester. Several months later she conceived and delivered a healthy baby at term. CONCLUSIONS: To our knowledge this is the first reported case of pregnancy after high-dose chemotherapy with stem cell transplant in a woman with ovarian carcinoma.

Adult↗
PubMed2001

Caring for colleagues.

Shortly before his death in 1995, Kenneth B. Schwartz, a cancer patient at Massachusetts General Hospital (MGH), founded the Kenneth B. Schwartz Center. The Schwartz Center is a non-profit organization dedicated to supporting and advancing compassionate health care delivery, which provides hope to the patient, support to caregivers, and sustenance to the healing process. The center sponsors the Schwartz Center Rounds, a monthly multidisciplinary forum where caregivers reflect on important psychosocial issues faced by patients, their families, and their caregivers, and gain insight and support from fellow staff members. Caring for colleagues who develop cancer is a privilege woven with an extra dimension-caregiver-patient issues. As well as stretching the usual need for a supportive relationship, when one of the health care team develops cancer it particularly provokes concerns about our own mortality. The case is presented of a well-known physician who developed a second cancer and has been cared for at the MGH Cancer Center Staff discuss her care as it has been effected by her status as a colleague. They perceived unique barriers to optimal care such as assumptions about the patient's level of medical knowledge, and technical, informational, emotional, and hierarchical issues that may obstruct the development of a trusting relationship between caregivers and the physician/patient. Emotional stress may prevent the sharing of an accurate prognosis. In the case under consideration, the patient had a frank and open attitude to her cancer yet her caregivers were concerned about continual breeches of patient confidentiality. Despite the many potential problems inherent when the caregiver becomes the patient, this case discussion was a poignant reminder of the unique challenges of every experience with cancer and the weighty privilege of being involved with patient care.

Adaptation, Psychological↗
PubMed2001

Ovarian cancer.

Ovarian cancer remains the most lethal gynecologic malignancy in women in the United States. Studies from this year's American Society of Clinical Oncology more clearly defined the role of chemotherapy in women with early stage disease and now suggest that essentially all women with invasive disease should receive chemotherapy that contains carboplatin. Studies in women with advanced disease continue to support the use of carboplatin and paclitaxel in the treatment of women with newly diagnosed disease although early data suggest that carboplatin and docetaxel might be an acceptable alternative. Platinum-resistant disease remains a therapeutic challenge. Small molecules that inhibit the function of the epidermal growth factor receptor, such as OSI-774, and novel classes of chemotherapeutic agents, including the acylfulvene MGI-114 and epothilone B and its analogue, BMS247550, all warrant further study in this disease.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed2001

Complementary, alternative, integrative, or unconventional medicine?

Shortly before his death in 1995, Kenneth B. Schwartz, a cancer patient at Massachusetts General Hospital (MGH), founded the Kenneth B. Schwartz Center. The Schwartz Center is a non-profit organization dedicated to supporting and advancing compassionate health care delivery, which provides hope to the patient, support to caregivers, and sustenance to the healing process. The center sponsors the Schwartz Center Rounds, a monthly multidisciplinary forum where caregivers reflect on important psychosocial issues faced by patients, their families, and their caregivers, and gain insight and support from fellow staff members. Interest in complementary and alternative medicine (CAM) has grown exponentially in the past decade, fueled by Internet marketing, dissatisfaction with mainstream medicine, and a desire for patients to be actively involved in their health care. There is a large discordance between physician estimates and reported prevalence of CAM use. Many patients do not disclose their practices mainly because they believe CAM falls outside the rubric of conventional medicine or because physicians do not ask. Concern about drug interactions and adverse effects are compounded by a lack of Food and Drug Administration regulation. Physicians need to be informed about CAM and be attuned to the psychosocial needs of patients.

Caregivers↗
PubMed2001

Phase I and pharmacokinetic study of ecteinascidin 743 administered as a 72-hour continuous intravenous infusion in patients with solid malignancies.

Ecteinascidin 743 (ET-743) is a cytotoxic tetrahydroisoquinoline alkaloid that covalently binds to DNA in the minor groove. The in vitro chemosensitivity of cancer cells to ET-743 is markedly enhanced by prolonging the duration of exposure to the drug. A Phase I study of ET-743 given as a 72-h continuous i.v. infusion every 21 days was performed. Characteristics of the 21 adult patients with refractory solid tumors enrolled in the study were as follows: (a) 12 men; (b) 9 women; (c) median age, 59 years; (d) Eastern Cooperative Oncology Group performance status < or = 1, 20 patients; and (e) two prior regimens of chemotherapy, 7 patients. Dose limiting toxicity (DLT) was defined by typical criteria, except that grade 3 transaminitis did not constitute a DLT. There were no DLTs in the six patients evaluated at the first two dose levels of 600 and 900 microg/m2. Reversible grade 4 transaminitis occurred in two of nine patients after treatment with the first cycle of therapy at the third dose level of 1200 microg/m2. Another patient experienced grade 4 rhabdomyolysis, renal failure requiring hemodialysis, grade 4 neutropenia, and grade 3 thrombocytopenia during the second cycle of therapy with this dose. The maximum tolerated dose was 1200 microg/m2, and an additional six patients were enrolled at an intermediate dose level of 1050 microg/m2. This well-tolerated dose was established as the recommended Phase II dose. The disposition of ET-743 was distinctly biexponential, and a departure from linear pharmacokinetic behavior was evident at the 1200-microg/m2 dose level. Pharmacokinetic parameters determined at 1050 microg/m2 were (mean +/- SD): maximum plasma concentration, 318 +/- 147 pg/ml; initial disposition phase half-life, 9.0 +/- 10.3 min; terminal phase half-life, 69.0 +/- 56.7 h; and total plasma clearance, 28.4 +/- 22.5 liters/h/m2. Prolonged systemic exposure to concentrations of the agent that are cytotoxic in vitro were achieved. Toxicity of the drug is clearly schedule-dependent, because increasing the duration of infusion from 3 or 24 h to 72 h results in decreased myelosuppression and comparable hepatotoxicity. Although there were no objective responses to therapy, clear evidence of antitumor activity was observed in a patient with epithelioid mesothelioma, as confirmed by positron emission tomography studies. A Phase II trial to assess the efficacy of ET-743 against this highly refractory neoplasm has been initiated on the basis of this observation. The therapeutically optimal administration schedule remains to be established, inasmuch as there have been indications of activity against a variety of tumors during Phase I studies when the drug was infused over times ranging from 1 to 72 h. Characterizing the pharmacokinetics of ET-743 during the course of Phase II trials and Phase I combination studies is recommended to assure that this promising new anticancer drug can be used with an acceptable margin of safety.

Adult↗
PubMed2000

Predictors of skeletal complications in patients with metastatic breast carcinoma.

BACKGROUND: The high rate of incidence of skeletal complications in women with metastatic breast carcinoma appears to contribute significantly to their morbidity. Although recent trials have demonstrated the efficacy of bisphosphonates in preventing skeletal complications in selected patients, to the authors' knowledge the incidence rate of skeletal complications in an unselected population of women with metastatic breast carcinoma is unknown. The current study was designed to examine the incidence rate of skeletal complications in a large unselected group of women with metastatic breast carcinoma to determine predictors of these complications. METHODS: All women (n = 718) diagnosed with metastatic breast carcinoma between 1981-1991 at the study institution were studied retrospectively. RESULTS: Greater than 50% of the women developed skeletal complications; among these women, 51% had > 1 complication. Approximately 80% of those with bone-limited disease at the time of diagnosis developed complications, as did 60% of those with bone and visceral disease and 21% of those with no bone disease. By univariate analysis, the site of initial metastatic disease, abnormal alkaline phosphatase, and a disease free interval of < 3 years were predictive of skeletal complications. Multivariate analysis revealed that bone involvement at the time of diagnosis was predictive of subsequent skeletal complications. CONCLUSIONS: In this large retrospective study with extensive follow-up, skeletal complications were extremely common and repetitive, although complications predated patient death by >/= 1 year in the group of women presenting with any bone disease. The presence of bone disease at the time of initial presentation was predictive of skeletal complications. In this group of patients, the authors were unable to identify a subgroup with a low rate of skeletal complications.

Bone Diseases↗
PubMed2000

A phase I study of gemcitabine and docetaxel in patients with metastatic solid tumors.

BACKGROUND: A Phase I study was initiated to determine the maximum tolerated dose of weekly gemcitabine combined with monthly, fixed-dose docetaxel. METHODS: Patients with metastatic solid tumors were treated with docetaxel, 60 mg/m(2), on Day 1 every 28 days. Gemcitabine was administered on Days 1, 8, and 15 and underwent dose adjustment in cohorts of 3-6 patients. At the maximum tolerated dose, 11 additional patients were enrolled. RESULTS: Twenty-six patients received 85 cycles of therapy. At the first dose level, the planned gemcitabine dose on Days 1, 8, and 15 was 800 mg/m(2). Two of the 6 patients treated at this dose level experienced dose-limiting toxicities (DLTs) requiring the reduction of gemcitabine to 600 mg/m(2) per dose and the administration of ciprofloxacin, 500 mg orally twice daily, on Days 8-18. At the second dose level the first 3 patients experienced no DLTs and the dose of gemcitabine was increased to 700 mg/m(2). Two of the 6 patients treated at the 700 mg/m(2) dose level experienced DLTs. Eleven additional patients were enrolled at the recommended Phase II dose of gemcitabine (600 mg/m(2)). At this dose level, Grade 3/4 (according the National Cancer Institute's common toxicity criteria) neutropenia and thrombocytopenia occurred in 12.5% and 2.1% of cycles, respectively. Grade 3 and 4 nonhematologic toxicities were uncommon. Three of seven evaluable patients with pancreatic carcinoma had evidence of significant antineoplastic activity (three partial responses). In addition, two complete responses (one patient with gastric carcinoma and one patient with ovarian carcinoma) and one partial response (patient with hepatocellular carcinoma) were noted in patients with other solid tumors. CONCLUSIONS: The regimen comprised of docetaxel, 60 mg/m(2), on Day 1 and gemcitabine, 600 mg/m(2), on Days 1, 8, and 15 with ciprofloxacin on Days 8-18 every 28 days is safe, well tolerated, and active.

Antimetabolites, Antineoplastic↗
PubMed2000

Communicating genetic risk: pros, cons, and counsel.

Shortly before his death in 1995, Kenneth B. Schwartz, a cancer patient at Massachusetts General Hospital (MGH), founded The Kenneth B. Schwartz Center at MGH. The Schwartz Center is a non-profit organization dedicated to supporting and advancing compassionate health care delivery, which provides hope to the patient, support to caregivers, and encourages the healing process. The center sponsors the Schwartz Center Rounds, a monthly multidisciplinary forum where caregivers reflect on important psychosocial issues faced by patients, their families, and their caregivers, and gain insight and support from fellow staff members. This case is of a woman with a personal, and a strong family history of breast cancer, who considered genetic testing for mutations in the BRCA1 and BRCA2 genes. The details of the case have been altered to protect the patient's anonymity. The patient was very anxious and there was disagreement between her healthcare providers about the potential benefits of genetic testing. The discussion of the case focused on several controversial issues, particularly the ownership of genetic information, and who is responsible for disseminating information to the family members at risk. The difficulties in communicating risk, providing emotional support and coping with the continuing uncertainties about screening and intervention are reviewed with an overview of the molecular biology, inheritance, and epidemiology of the BRCA1 and BRCA2 genes.

Adaptation, Psychological↗
PubMed1999

TRAG-3, a novel gene, isolated from a taxol-resistant ovarian carcinoma cell line.

The mechanisms responsible for the development of the taxol resistance phenotype are unclear, and are likely explained by multiple mechanisms. To understand the molecular changes associated with drug resistance more fully, a taxol-resistant subline, derived from the human ovarian cancer cell line SKOV-3, was established through selection by culture in incrementally increasing taxol concentrations. Comparison of SKOV-3 to SKOV-3TR by differential display identifies a new gene, TRAG-3 (Taxol Resistance Associated Gene- 3). In comparison to the parental line, SKOV-3, TRAG-3 mRNA is overexpressed in the taxol-resistant cell line SKOV-3TR. The nucleotide sequence of the TRAG-3 cDNA contains an open reading frame of 333bp that predicts for a protein product of 110 amino acids. A GenBank search identifies a cosmid clone containing a genomic sequence corresponding to that of TRAG-3. DNA and protein analysis reveals that TRAG-3 has no homology to any known cDNAs or proteins. Northern analysis demonstrates that TRAG-3 is overexpressed in the taxol-resistant breast cancer cell line MDA 435TR as well as the doxorubicin-resistant multiple myeloma cell lines 8226/DOX40 and 8226/MDR10V. A survey of normal tissue shows minimal or absent TRAG-3 mRNA expression. Screening of a wide variety of cancer cell lines demonstrates TRAG-3 expression in many cell lines derived from different tissue types. In summary, TRAG-3 is a novel gene whose expression is associated with the chemotherapy-resistant and neoplastic phenotype.

Amino Acid Sequence↗
PubMed1999

Adaptation of solid phase extraction to an automated column switching method for online sample cleanup as the basis of a facile and sensitive high-performance liquid chromatographic assay for paclitaxel in human plasma.

An improved method for assaying paclitaxel in human plasma by high-performance liquid chromatography (HPLC) with UV detection at 227 nm has been developed by adapting previously reported sample preparation methods and chromatographic conditions to facilitate semi-automated sample cleanup using a column switching technique. Manual sample manipulations were limited to isolating the drug and internal standard from plasma (1.0 ml) by liquid-liquid extraction using tert-butyl methyl ether. The sample extract was initially loaded onto a short cartridge column containing a cyanopropyl stationary phase. During the predetermined time interval that the drug and internal standard eluted from the cartridge, 1.50-2.20 min, a fully automated 6-position switching valve was used to direct the effluent onto an octylsilica analytical column. The same mobile phase, composed of acetonitrile-methanol-ammonium acetate buffer (pH 5.0; 20 mM) (76:19:105, v/v/v) and delivered at flow rate of 1.0 ml/min, was used for both separations. The overall retention times of paclitaxel and the internal standard were 10.9 and 18.1 min, respectively. The analytical method was thoroughly validated for quantitating paclitaxel in plasma at concentrations ranging from 6 to 586 nM (5-500 ng/ml). The lowest concentration of paclitaxel measured with acceptable day-to-day accuracy (100.2%) and precision (RSD 11.7%, n = 21, 5 months) was 6 nM (5 ng/ml). The sensitivity and selectivity of the assay proved to be more than adequate for monitoring steady-state plasma concentrations of the drug when administered to cancer patients as a 96 h continuous intravenous infusion in combination with other anticancer agents, such as doxorubicin and topotecan. Moreover, the heart-cutting procedure prevented the problematic introduction of interfering nonpolar plasma components onto the analytical column, thereby enhancing sample throughput while decreasing the technical demands of the assay. The method was found to be extremely reproducible and robust during extended use for the routine analysis of plasma specimens acquired from several clinical trials.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1999

High dose chemotherapeutic strategies in the treatment of epithelial ovarian carcinoma.

High dose chemotherapy with stem cell rescue has been used in an attempt to overcome chemotherapy resistance and increase survival in patients with poor prognosis epithelial ovarian cancer. Untreated patients with advanced stage disease and those with chemosensitive recurrent disease do better in terms of response rates as well as duration of response and overall survival. Newer strategies using multiple cycles of dose intense therapy may improve results although it will be difficult to document changes in the natural history of advanced ovarian cancer without the completion of randomized phase III trials.

Antineoplastic Agents↗
PubMed1999

A staff dialogue on caring for a cancer patient who commits suicide: psychosocial issues faced by patients, their families, and caregivers.

Shortly before his death in 1995, Kenneth B. Schwartz, a cancer patient at Massachusetts General Hospital (MGH), founded The Kenneth B. Schwartz Center at MGH. The Schwartz Center is a non-profit organization dedicated to supporting and advancing compassionate health care delivery which provides hope to the patient, support to caregivers, and encourages the healing process. The Center sponsors the Schwartz Center Rounds, a monthly multidisciplinary forum during which caregivers discuss a specific cancer patient, reflect on the important psychosocial issues faced by patients, their families, and their caregivers, and gain insight and support from their fellow staff members. The case presented was of a 31-year-old man who developed adenocarcinoma of the lung with painful bone metastases. His tumor was unresponsive to treatment and he subsequently committed suicide by shooting himself. The verbatim and subsequent discussion raised a number of issues. Staff were devastated by the violent way that he ended his life. They questioned whether more could have been done to prevent this outcome, yet acknowledged that it mirrored the way he had lived, and were able to discuss the values by which we live and die. Some, but not all, felt that the patient had the right to choose how and when to end his life.

Adenocarcinoma↗