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Biomedical subjects

M Markman

Publications and source records attributed to M Markman.

At least 271 records · Page 15Linked to original sources
PubMed1989

Serum CA 125 levels and surgical findings in patients undergoing secondary operations for epithelial ovarian cancer.

Serum CA 125 levels and surgical findings were prospectively compared in 96 secondary laparotomies performed on patients with epithelial ovarian cancer. All patients had documentation of an elevated CA 125 level (greater than 35 U/ml) at a time when ovarian cancer was present, and thus the tumors were known to be "marker positive." Operation was performed in 45 patients who were clinically free of disease and in 51 patients in whom there was clinical evidence of disease. At the time of operation, 29 patients had normal CA 125 levels; persistent disease was documented in 18 (62%) of these. Of the patients with normal CA 125 levels at the time of operation, those with persistent disease had a significantly higher mean CA 125 level (16.9) than those with no disease detected (8.8, p = 0.001). At exploration, cancer was found in 84 patients. There was a correlation between the maximum diameter of the largest residual tumor mass and the accuracy of the CA 125 level as follows: microscopic to 1 cm disease, 55% accuracy; greater than 1 to 5 cm disease, 80% accuracy; greater than 5 cm disease, 92% accuracy (p = 0.013). There was no correlation of CA 125 accuracy with the patient's age, number of months from initial diagnosis, tumor stage, grade, or cell type, or the highest-ever level of CA 125. Of the 84 patients with tumor found at exploration, 66 had elevated CA 125 levels, yielding a sensitivity of 78.5%. There were 12 patients with no tumor found at exploration; 11 of these had normal CA 125 levels. The one patient who had an elevated CA 125 level subsequently had a recurrence; the corrected specificity is thus 100%. An elevated CA 125 level is an accurate predictor of persistent disease. Most of these patients will have gross tumor present. The accuracy of the CA 125 level in detecting disease is related to the amount of tumor present. In our population, the predictive value of an elevated CA 125 level was 100%; the predictive value of a normal CA 125 level was 38%.

Adult↗
PubMed1989

Intraperitoneal cisplatin and etoposide in the treatment of refractory/recurrent ovarian carcinoma.

To determine the efficacy of a 6-month course of combination intraperitoneal (IP) chemotherapy with cisplatin and etoposide in patients with refractory or recurrent advanced ovarian carcinoma, 67 patients were entered into this prospective, nonrandomized, single-institution trial. Cisplatin at 100 mg/m2 and etoposide at 200 mg/m2 were administered IP on day 1 every month for 6 months. Exploratory laparotomy was performed before protocol entry and was planned after the completion of 6 months of IP therapy to surgically document response. All patients had received prior intravenous (IV) chemotherapy with a cisplatin-based regimen. At protocol entry, 18 (27%) patients had surgically defined residual tumor (maximal tumor diameter) greater than 2.0 cm, 17 (25%) patients greater than 0.5 cm - less than or equal to 2.0 cm, and 32 (48%) patients less than or equal to 0.5 cm. Sixteen patients (24%) who had experienced a treatment-free interval of more than 1 year prior to study entry were considered as having recurrent disease and the remaining 51 (76%) patients were considered as having refractory disease. Toxicity was tolerable: four patients (6%) had nadir fever, three (4%) had culture-documented bacterial peritonitis, five (7%) had IP catheter-related complications, and 27 (40%) had an increase in serum creatinine greater than 1.5 mg/dL. Among the 57 patients who are fully evaluable for response, the overall surgically defined response rate, complete (CR), and partial response (PR), was 40% (23/57), and the CR rate was 21% (12/57). Among the patients with recurrent disease, eight of 13 (62%) responded, with responses seen among all categories of residual disease. Among the patients with refractory disease, 15 of 44 (34%) had surgically documented responses. However, responses were more frequent in patients with residual disease less than 0.5 cm; 11 of 20 (55%) versus four of 24 (17%) with residual greater than 0.5 cm, P = .019 (chi 2, one degree of freedom, Yates correction). The duration of the CRs ranges from 4 to 18+ months. Longer follow-up is needed to determine if there is any impact on survival.

Adult↗
PubMed1989

Issues involved in providing quality and optimal care for the cancer patient in the era of cost containment.

With increasing emphasis on cost containment in the health care field there is legitimate concern that the quality of medical care provided by health professionals and hospitals will deteriorate. There is no area of medicine where this fear is more evident than in the care of the patient with malignant disease. Treatment is often palliative, making quality difficult to evaluate and the costs of therapy and supportive care are among the highest in the health care arena. In the future it can be anticipated that the conflict between cost and the provision of quality/optimal care for the patient with or suspected to have cancer will increase.

Cost Control↗
PubMed1989

Stability of floxuridine and leucovorin calcium admixtures for intraperitoneal administration.

The stability of floxuridine and leucovorin calcium in admixtures of 0.9% sodium chloride injection at various concentrations, temperature conditions, and time points was determined. Admixtures of floxuridine and leucovorin calcium were prepared in 1-L plastic bags containing 0.9% sodium chloride injection. Admixtures containing the following three concentrations were prepared: floxuridine 1 g and leucovorin calcium 30 mg, floxuridine 2 g and leucovorin calcium 240 mg, and floxuridine 4 g and leucovorin calcium 960 mg. The admixtures were stored at refrigerated temperature (4-8 degrees C), ambient room temperature (20 degrees C), and near-physiologic body temperature (40 degrees C). Drug concentrations were measured with a stability-indicating high-performance liquid chromatographic (HPLC) method at 0, 4, 8, 24, and 48 hours (4-8 degrees C) and at 0, 1, 3, 6, 24, and 48 hours (20 degrees C and 40 degrees C). A second set of samples at the same concentrations was prepared and sequentially stored at refrigerated, room, and near-physiologic temperatures to simulate actual-use conditions; these samples were assayed by HPLC at 0, 4, 8, 24, and 48 hours (4-8 degrees C); 49, 51, 54, and 60 hours (20 degrees C); and 61, 63, 66, and 72 hours (40 degrees C). All solutions were protected from light. Floxuridine and leucovorin calcium were stable at each concentration and temperature condition tested for a minimum of 48 hours. However, leucovorin calcium was more subject to decomposition at near-physiologic temperature than at other temperatures, with the most degradation at the lowest concentration.(ABSTRACT TRUNCATED AT 250 WORDS)

Chromatography, High Pressure Liquid↗
PubMed1989

Intraperitoneal chemotherapy as treatment for ovarian carcinoma and gastrointestinal malignancies: the Memorial Sloan-Kettering Cancer Center experience).

Several different chemotherapy trials via either combined systemic and intraperitoneal or only via the intraperitoneal route were investigated. The administration of systemically and intraperitoneally infused 5-fluorouracil (5-FU) in patients with ovarial carcinoma did not shown in any patient a complete or partial remission, but showed severe side effects. In a patient with a metastasizing adeno carcinoma of the appendix this chemotherapy protocol led to a complete remission. Investigations with intraperitoneally infused cisplatin showed that 50% of all patients came into remission with tumor nodules less than 0.5 cm, but showed only 20% objective remissions in patients with tumor nodules greater than 0.5 cm. The intraperitoneal administration of mitoxantrone showed in several patients with cisplatin refractory ovarial carcinoma tumor remission with, however, severe local toxicity.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1989

Intraperitoneal cisplatin chemotherapy in the management of ovarian carcinoma.

Phase I trials of the intraperitoneal (IP) administration of cisplatin have demonstrated that the drug can be safely delivered by this route with a major increase in exposure (approximately tenfold to 15-fold) of the cavity to the cytotoxic agent compared with that of the systemic circulation. Phase I trials of IP cisplatin in refractory ovarian carcinoma have shown that 30% to 50% of patients with small-volume residual disease (following systemically delivered cisplatin-based therapy) can be anticipated to experience a surgically documented response. While the ultimate role for cisplatin-based IP therapy in the standard management of ovarian carcinoma remains to be defined, it appears that at least a subset of patients with this malignancy (those with very small tumor nodules or microscopic disease only) may benefit from the institution of this therapeutic approach.

Carcinoma↗
PubMed1988

Uridine pharmacokinetics in cancer patients.

The availability of uridine can alter the sensitivity of tumor cells to antimetabolites such as N-phosphonacetyl-L-aspartic acid (PALA) and acivicin by virtue of the cell's ability to salvage preformed metabolites from its environment. We investigated the pharmacokinetics of physiologically relevant amounts of uridine in cancer patients in a pilot study to further our understanding of uridine metabolism in the human body. Four cancer patients, two males and two females, were given an i.v. bolus of a trace amount of radiolabeled uridine. The nucleoside disappeared from the plasma in a triphasic manner, with initial half-lives of 0.57 +/- 0.28 and 1.79 +/- 0.62 min and a terminal half-life of 17.5 +/- 7.3 min. The volume of distribution was 481 +/- 70 ml/kg, and the plasma uridine clearance was calculated to be 1.70 +/- 0.42 l/min. Simultaneous plasma and bone marrow uridine concentrations were measured in a separate group of seven healthy volunteers. The uridine concentration in plasma was 2.32 +/- 0.58 microM, and that in the bone marrow plasma was 10.44 +/- 5.06 microM. These results suggest a very rapid turnover of uridine in the plasma when the nucleoside is present at physiologic concentrations, and that there is a locally high concentration of uridine available for salvage in the bone marrow.

Adult↗
PubMed1988

Recurrence after negative second-look laparotomy for ovarian cancer: analysis of risk factors.

To determine the long-term rate of recurrence and define risk factors for recurrence, we have analyzed clinical information on 83 patients followed up for a minimum of 4 years (median, 69 months) after negative second-look laparotomy. Overall, 21 of 83 patients (25.3%) had a recurrence. Median interval to recurrence was 14 months. Stage, grade, and type of chemotherapy were significantly related to risk of recurrence. In patients with stage I disease only one of 27 (3.7%) had a recurrence. Patients with stage I disease were not included in further analysis of risk factors. In stages II, III, and IV, 20 of 56 patients (35.7%) had a recurrence. Recurrence rates by grade (excluding stage I) are as follows: grade 1, three of 21 (14.3%); grade 2, six of 17 (35.5%), and grade 3, 11 of 17 (64.7%). Platinum-treated patients in stages II, III, and IV had a 50% (12/24) recurrence rate compared with 25% in nonplatinum-treated patients (8/32) (p = 0.05). Differences in disease-free survival between platinum- and nonplatinum-treated patients were significant at the p = 0.02 level. When treated with platinum-based regimens, more patients will achieve complete clinical remission and subsequently negative second-look laparotomy. However, the recurrence rate in these patients is considerably higher than that in patients treated for longer durations with nonplatinum regimens.

Antineoplastic Agents↗
PubMed1988

Phase I trial of concurrent intraperitoneal and continuous intravenous infusion of fluorouracil in patients with refractory cancer.

In an effort to maximize both local-regional and systemic drug exposure to tumor in the peritoneal cavity, a phase I study was conducted that examined the simultaneous daily intraperitoneal (IP) and continuous intravenous infusion (CVI) of fluorouracil (5-FU) to 32 patients with refractory cancer. IP 5-FU administered at 1,000 mg/d with concurrent 5-FU by CVI at 1,000 mg/m2/d for four consecutive days was well tolerated. One patient with a primary gastrointestinal (GI) malignancy with minimal volume disease experienced a surgically defined complete remission. In theory, this regimen may demonstrate clinical utility as an adjuvant treatment of certain GI malignancies. Future studies are planned in this clinical setting.

Drug Administration Schedule↗
PubMed1988

A phase I trial of intraperitoneal recombinant gamma-interferon in advanced ovarian carcinoma.

The interferons are a class of biological agents that have demonstrated antineoplastic activity in a variety of tumors both in vitro and in vivo. Previous reports have suggested that interferons can be safely administered by the intraperitoneal (IP) route with a pharmacokinetic advantage for peritoneal cavity exposure compared with the systemic circulation and with objective antitumor activity being demonstrated. On the basis of these reports and laboratory data suggesting activity for recombinant gamma-interferon (r-GIFN) against several malignant cell lines, we treated 27 refractory ovarian carcinoma patients, including six with very-small-volume residual disease, with this agent delivered by the IP route. While r-GIFN was found to be remarkably well tolerated, with a 150- to 200-fold pharmacokinetic advantage for peak levels achieved in the peritoneal cavity compared with the plasma, no objective responses were observed. Despite the lack of demonstrated activity for single-agent IP-administered r-GIFN in this clinical setting, there remains considerable interest in this agent when delivered by the IP route because of in vitro data suggesting concentration-dependent synergy between r-GIFN and other biological agents.

Adult↗
PubMed1988

Chemotherapy with curative potential in small cell carcinoma of the lung.

Despite response rates to combination chemotherapy regimens approaching 90 per cent, long-term survival is experienced by less than 10 per cent of patients with small cell carcinoma of the lung. Recent efforts to improve the efficacy of therapy have focused on the combined use of radiation and chemotherapy, alternating non-cross resistant chemotherapeutic regimens, dose intensification, and performance of surgery for selected patients with limited-stage disease.

Carcinoma, Small Cell↗
PubMed1988

Chemotherapy in ovarian carcinoma: intravenous or intraperitoneal?

Although the majority of women with advanced ovarian carcinoma respond to cisplatin-based intravenous chemotherapy, long-term survival is experienced by less than 30 per cent of treated patients. Efforts to improve the efficacy of treatment have focused on dose intensification and direct drug delivery into the peritoneal cavity.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1988

Supportive care.

Explore the source record for details and available documents.

Antiemetics↗
PubMed1988

Peritoneal cytology as an indicator of disease in patients with residual ovarian carcinoma.

Cytologic assessment of peritoneal washings or ascites in ovarian cancer patients has been suggested as a method of evaluating response to therapy or disease status, although the accuracy of this technique has not been clearly established. Ascitic fluid or peritoneal washings were obtained during 96 reassessment laparotomies that were biopsy-positive for residual intraperitoneal ovarian cancer. Cytologic studies done on these samples failed to detect malignant cells in 66% of the cases with gross residual disease and 78% of the cases with only microscopic residual disease on biopsy. The accuracy of peritoneal cytology in detecting residual ovarian cancer was unrelated to residual tumor size, original clinical stage, histologic tumor grade, and tumor cell type. Examination of ascitic fluid found at the time of surgery was somewhat more reliable than assessment of peritoneal washings, although this difference was of borderline statistical significance. Peritoneal cytology cannot reliably detect residual ovarian cancer after initial treatment with surgery and chemotherapy. Negative peritoneal cytology is frequently seen in the presence of gross residual tumor.

Ascitic Fluid↗
PubMed1987

Phase I/pharmacokinetic study of intraperitoneal cisplatin and etoposide.

We administered cisplatin and etoposide by peritoneal dialysis to 39 patients with i.p. malignancies in order to investigate the toxicity, pharmacokinetics, and clinical activity of this 2-drug combination. All patients received i.v. sodium thiosulfate concurrently with the i.p. chemotherapy. Myelosuppression, nausea, vomiting, and malaise were the primary toxicities encountered. The maximum tolerated dose of etoposide was 350 mg/m2, when administered with a fixed dose of cisplatin, 200 mg/m2. Although the total (free and protein-bound) etoposide exposure for the peritoneal cavity was only 1.5-fold greater than that for the plasma, the free (non-protein bound) etoposide peritoneal exposure was 65-fold greater than the plasma. Tumor regressions were noted in patients with ovarian and pancreatic carcinomas. This study is the first demonstration of the large pharmacokinetic advantage that exists for the i.p. administration of highly protein-bound drugs, and it also documents the clinical activity of i.p. cisplatin and etoposide.

Abdomen↗
PubMed1987

Phase I trial of combination therapy of cancer with N-phosphonacetyl-L-aspartic acid and dipyridamole.

While N-phosphonacetyl-L-aspartic acid (PALA), an inhibitor of de novo pyrimidine biosynthesis, demonstrated a unique spectrum of activity during preclinical drug evaluation, multiple clinical trials have shown it to possess minimal clinical activity. One explanation for the disappointing results is the possibility that tumor cells are able to utilize circulating uridine in the synthesis of pyrimidines (salvage pathway). Dipyridamole, an inhibitor of nucleoside transport, has been demonstrated experimentally to potentiate the cytotoxicity of PALA significantly. In addition, this agent has a long safety record when used clinically in man. A phase I trial of this two-drug combination was therefore conducted, with a fixed oral dose of dipyridamole (50 mg/m2 every 6 h) and an escalating i.v. dose of PALA administered every 3 weeks. The dose-limiting toxicity with this schedule was diarrhea and abdominal cramping pain at a PALA dose of 3900-4200 mg/m2. Among the 65 patients participating in this trial 4 objective responses (2 partial, 2 minimal) were observed. Because of the potential for unique clinical synergy between PALA and dipyridamole further investigation should be considered.

Adult↗