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Biomedical subjects

M Markman

Publications and source records attributed to M Markman.

At least 73 records · Page 4Linked to original sources
PubMed1999

Lack of efficacy of 24-h infusional topotecan in platinum-refractory ovarian cancer: A Gynecologic Oncology Group trial.

BACKGROUND: The aim of this study was to evaluate the efficacy of a more convenient topotecan administration schedule in the second-line treatment of advanced platinum-refractory ovarian cancer. METHODS AND MATERIALS: The Gynecologic Oncology Group conducted a Phase II trial of 24-h infusional topotecan (8.5 mg/m(2)), repeated every 3 weeks in 26 patients with platinum-refractory ovarian cancer (failure to respond to initial platinum-based treatment or development of recurrent disease within 6 months of completion of chemotherapy). RESULTS: Grade 4 neutropenia (85% of patients) and thrombocytopenia (12%) were the major toxicities encountered. Of the 25 patients evaluable for response, only a single patient experienced an objective response (4%). CONCLUSIONS: When employed at this dose and schedule (24-h infusion every 3 weeks), topotecan has minimal second-line activity in platinum-refractory ovarian cancer.

Adult↗
PubMed1999

An effective and more convenient drug regimen for prophylaxis against paclitaxel-associated hypersensitivity reactions.

"Standard" prophylaxis for paclitaxel-associated hypersensitivity reactions has included the systemic administration of H1 and H2 histamine antagonists, along with oral dexamethasone taken both the night prior to, and the morning of, each paclitaxel treatment. To improve patient convenience and compliance with steroid delivery, the Gynecologic Cancer Program of the Cleveland Clinic Foundation has treated patients with an all-intravenous prophylaxis regimen (diphenhydramine 50 mg, famotidine 20 mg, dexamethasone 20 mg) given 30 min prior to paclitaxel (without any earlier oral steroid dosing). To date, we have treated more than 200 patients who received all courses of paclitaxel with this simplified prophylactic regimen, of whom approximately 9% developed hypersensitivity reactions (major or minor). This incidence is comparable to our previously reported experience with hypersensitivity reactions in a similar number of patients receiving the standard prophylaxis (including oral dexamethasone) with their initial course of paclitaxel, and subsequent cycles employing this all-intravenous program. We conclude that this "modified" regimen for paclitaxel-associated hypersensitivity reactions (with all drugs administered approximately 30 min prior to the delivery of paclitaxel) is as effective as, and more convenient than, the standard regimen, and avoids delaying chemotherapy as a result of a patient failing to remember to take one or both oral steroid doses.

Anti-Inflammatory Agents↗
PubMed1999

Serum CA-125 as a marker of disease activity in uterine papillary serous carcinoma.

Papillary serous carcinoma of the endometrium exhibits many clinical features of ovarian cancer, including a high metastatic potential and response to platinum-based chemotherapy. We investigated the clinical utility of the serum CA-125 antigen level, an established marker of response or progression in ovarian cancer, to serve as a indicator of these events in patients with this highly malignant subtype of endometrial cancer. Of 21 individuals with this cancer treated in our program from 11/91 to 6/97, 16 had baseline CA-125 determinations prior to the administration of chemotherapy, of whom 13 were elevated above the normal range. Of these 13 patients, 8 (57%) experienced either a major reduction or normalization of CA-125 levels following therapy, consistent with their clinical course at that point in time. Similarly, of 11 patients who ultimately relapsed, 8 (73%) were found to have a rise in the CA-125 antigen level which closely corresponded to, or proceeded, clinical relapse. A single patient was demonstrated to have disease progression with a declining level of CA-125. We conclude the serum CA-125 antigen level is a useful indicator of disease response or progression in individuals with papillary serous carcinoma of the endometrium.

Aged↗
PubMed1999

Clinical features of hypersensitivity reactions to carboplatin.

PURPOSE: To characterize the clinical features of carboplatin-associated hypersensitivity reactions. PATIENTS: Patients with gynecologic malignancies treated at the Cleveland Clinic Foundation from June 1995 through July 1998 who experienced a carboplatin-associated hypersensitivity reaction were the subjects of this evaluation. RESULTS: Of the 205 patients treated with carboplatin during this time period, 24 (12%) developed a carboplatin hypersensitivity reaction. The median number of platinum (carboplatin plus cisplatin) courses for the first episode was eight (range, six to 21). Only three patients (13%) developed this toxicity during their initial chemotherapy regimen, with the remainder experiencing a reaction during their second (n = 15) or third (n = 6) carboplatin treatment program for recurrent disease. Thirteen patients (54%) developed at least moderately severe symptoms (diffuse erythroderma, tachycardia, chest tightness, wheezing, facial swelling, dyspnea, hypertension, or hypotension). In approximately one half of patients, the reaction developed after more than 50% of the carboplatin had been infused. Only one of three patients was successfully treated with the agent upon rechallenge. CONCLUSION: Carboplatin hypersensitivity reactions develop in patients who have been extensively pretreated with the agent. The clinical features are highly variable, but they are sufficiently different from those noted after the administration of paclitaxel that it should not be difficult to distinguish between reactions to the two agents. As carboplatin is increasingly used as initial and second-line chemotherapy of ovarian cancer and other malignancies, it can be anticipated that hypersensitivity reactions to the drug will become a more common and difficult clinical management issue.

Adult↗
PubMed1999

Diagnosis and management of superior vena cava syndrome.

Superior vena cava (SVC) syndrome is a relatively common complication of lung cancer or lymphoma, and in fact is often the initial manifestation of these diseases. However, benign causes also exist, and physicians should not automatically assume that SVC syndrome is due to cancer. A definitive histologic diagnosis of cancer should be obtained before starting radiotherapy or chemotherapy to treat SVC syndrome.

Aortic Aneurysm↗
PubMed1999

Intraperitoneal chemotherapy in the management of colon cancer.

Intraperitoneal delivery of cytotoxic agents active in the treatment of colon cancer has the potential to significantly increase the exposure to these drugs to cancer present within the peritoneal cavity or liver. To date, few well-controlled clinical trials have been conducted to test the relative efficacy of this strategy compared with systemic drug delivery. A major issue is the small number of useful cytotoxic agents in colon cancer, and the limited ability of the drugs to penetrate directly into tumor tissue following regional delivery. Intraperitoneal antineoplastic drug administration has its greatest therapeutic potential as an adjuvant treatment strategy for individuals with colon cancer and a high risk for recurrence in the peritoneal cavity or liver.

Antineoplastic Agents↗
PubMed1999

Supportive care.

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Animals↗
PubMed1998

Lysophosphatidic acid as a potential biomarker for ovarian and other gynecologic cancers.

CONTEXT: Lysophosphatidic acid (LPA) has been shown to stimulate proliferation of ovarian cancer cells and is present in the ascitic fluid of patients with ovarian cancer. OBJECTIVES: To determine whether elevated levels of LPA are present in plasma from patients with ovarian cancer and other gynecologic malignancies compared with healthy controls and to evaluate whether an elevated LPA plasma level may be a biomarker for these diseases. DESIGN: A research assay was used to measure total LPA levels in plasma from healthy women and women with different diseases. All LPA assays and comparison of LPA levels and CA125 (an ovarian cancer biomarker) levels were performed by observers blinded to patient status or group. SETTING: The Cleveland Clinic Foundation. PARTICIPANTS: A convenience sample of 48 healthy control women, 48 women with ovarian cancer, 36 women with other gynecologic cancers, 17 women with benign gynecologic diseases, 11 women with breast cancer, and 5 women with leukemias. MAIN OUTCOME MEASURES: Total LPA levels in plasma samples from patients and controls. RESULTS: Patients in the ovarian cancer group had significantly higher plasma LPA levels (mean, 8.6 micromol/L; range, 1.0-43.1 micromol/L) compared with the healthy control group (mean, 0.6 micromol/L; range, <0.1-6.3 micromol/L) (P<.001). Elevated plasma LPA levels were detected in 9 of 10 patients with stage I ovarian cancer, 24 of 24 patients with stage II, III, and IV ovarian cancer, and 14 of 14 patients with recurrent ovarian cancer. Of 36 patients with other gynecologic cancers, 33 also showed higher LPA levels(mean, 14.9 micromol/L; range, <0.1-63.2 pmol/L), compared with healthy controls (P<.001). Elevated plasma LPA levels were detected in 5 of 48 controls and 4 of 17 patients with benign gynecologic diseases and in no women with breast cancer or leukemia. In comparison, among a subset of patients with ovarian cancer, 28 of 47 had elevated CA125 levels, including 2 of 9 patients with stage I disease. CONCLUSIONS: Plasma LPA levels may represent a potential biomarker for ovarian cancer and other gynecologic cancers. However, these findings are preliminary and require confirmation in larger studies.

Adult↗
PubMed1998

High expression of the HMG box factor sox-13 in arterial walls during embryonic development.

Members of the Sox gene family of transcription factors are defined by the presence of an 80 amino acid homology domain, the High Mobility Group (HMG) box. Here we report the cloning and initial analysis of murine Sox-13 . The 984 amino acids Sox-13 protein contains a single HMG box, a leucine zipper motif and a glutamine-rich stretch. These characteristics are shared with another member of the Sox gene family, Sox-6. High level embryonic expression of Sox-13 occurs uniquely in the arterial walls of 13.5 days post coitum (dpc) mice and later. Low level expression was observed in the inner ear of 13.5 dpc mice and in a limited number of cells in the thymus of 16.5 dpc mice, from which Sox-13 was originally cloned. At 18.5 dpc, Sox-13 is expressed in the tracheal epithelium below the vocal cord and in the hair follicles. The Sox-13 protein binds to the consensus HMG box motif, AACAAAG, but does not transactivate transcription through a concatamer of this motif. Sox-13, like other members of the Sox family likely plays an important role in development.

Amino Acid Sequence↗
PubMed1998

Altretamine (hexamethylmelamine) in platinum-resistant and platinum-refractory ovarian cancer: a Gynecologic Oncology Group phase II trial.

OBJECTIVES: In an effort to critically examine the antitumor activity of altretamine (hexamethylmelamine) as salvage therapy of platinum-refractory ovarian cancer, the Gynecologic Oncology Group initiated a Phase II trial of the agent administered in this clinical setting. METHODS: Altretamine was administered at a dose of 260 mg/m2 orally for 14 days in a 28-day course. Treatment was continued until disease progression or unacceptable side effects prevented further therapy. A total of 36 patients (median age: 56.5) were treated on this trial, of whom 33 were evaluable for toxicity and 30 for response. All patients had previously received either cisplatin or carboplatin and paclitaxel. RESULTS: The major side effect was emesis (grade 3-4, 7/33, 21%). The objective response rate was 10% (one complete response, two partial responses). CONCLUSION: We conclude that altretamine has limited activity in platinum-refractory ovarian cancer.

Administration, Oral↗
PubMed1998

Phase 2 trial of moderately high dose single agent mitoxantrone in platinum and paclitaxel-refractory ovarian cancer.

In the human clonogenic assay, mitoxantrone possesses among the steepest dose-response curves of any cytotoxic agent against ovarian cancer. To test the potential clinical relevance of this observation, we conducted a phase 2 trial of moderately high dose single agent mitoxantrone (28 mg/m2 delivered every 3-4 weeks) along with granulocyte-macrophage colony stimulating factor (250 micrograms/m2/day beginning 24 h after mitoxantrone and continuing until neutrophil recovery) in 34 patients with clinically defined platinum and paclitaxel-refractory ovarian cancer. The major toxicity of treatment was severe neutropenia which was almost universal. However, there were no treatment-related infectious deaths. Significant cardiac toxicity was not observed. Five of 33 evaluable patients demonstrated objective evidence of a response to treatment (1 patient achieving a partial response of measurable tumor masses, 4 patients achieving a > or = 50% reduction in CA-125 antigen level), with a median duration of response of 3 months (range 2-5 months). We conclude that moderately high dose mitoxantrone has definite, although very limited, single agent activity in platinum and paclitaxel-refractory ovarian cancer. Unfortunately, as this regimen produces severe hematologic toxicity and response durations are short, it cannot be recommended for routine clinical use. The role of an even higher dose mitoxantrone schedule employed as a component of a high dose chemotherapy program with bone marrow or peripheral progenitor cell protection in the treatment of ovarian cancer remains to be defined.

Adult↗
PubMed1998

Phase 2 trial of single agent ifosfamide/mesna in patients with platinum/paclitaxel refractory ovarian cancer who have not previously been treated with an alkylating agent.

Ifosfamide has been shown to possess modest activity in patients with platinum/cyclophosphamide refractory ovarian cancer. Current standard initial chemotherapy for ovarian cancer does not include an alkylating agent (paclitaxel substituting for cyclophosphamide). To evaluate the activity of ifosfamide in patients with refractory ovarian cancer who had not previously received an alkylating agent, 21 patients with platinum/paclitaxel refractory disease were treated with the drug as a single agent (1.8 g/m2/day x 3 days, with treatment repeated every 28 days). Treatment was reasonably well tolerated in most patients, although 1 individual was removed from study secondary to neurotoxicity. One patient exhibited an objective response of measurable disease, while a second individual had a major decrease in CA-125 levels (no measurable disease present) following therapy. An additional patient experienced disappearance of severe pelvic pain following treatment but failed to meet the criteria for a partial response. We conclude that ifosfamide has modest activity in platinum/paclitaxel refractory ovarian cancer. However, the level of effectiveness does not appear to be increased in individuals who are alkylating-agent naive, compared to previously reported experience in patients with prior exposure to this class of cytotoxic drugs (10-15% response rate).

Adult↗
PubMed1998

Experience with platinum-paclitaxel chemotherapy in the initial management of papillary serous carcinoma of the peritoneum.

OBJECTIVE: The objective of this study was to assess the activity and toxicity of combination platinum-paclitaxel chemotherapy in the initial management of patients with papillary serous carcinoma of the peritoneum (PSCP). METHODS: Patients initially treated at The Cleveland Clinic Foundation (CCF) for PSCP with platinum-paclitaxel combination chemotherapy regimens were identified and clinical information was abstracted by chart review. Toxicity data, progression-free survival, and overall survival were determined. RESULTS: Thirty-eight patients (36 Stage IIIC and 2 Stage IV) were identified. All chemotherapy was administered as outpatient infusions. All patients received paclitaxel (135 or 175 mg/m2) and 12 received cisplatin and 26 carboplatin. Two hundred thirty-two cycles were administered, with only three (1.3%) episodes of grade 3 toxicity and no grade 4 toxicity. Ninety-two percent of patients experienced at least a 50% reduction in their CA-125 levels and 55% experienced a greater than 90% reduction. Median progression-free survival (Kaplan-Meier) was 15 months and median overall survival was 40 months. Survival for optimally debulked patients (median not yet reached with median follow-up of 24 months) was significantly better than for suboptimally debulked patients (median 32.8 months) (P = 0.012). CONCLUSION: Platinum-paclitaxel chemotherapy regimens have substantial utility in the initial management of PSCP patients. The toxicity profile is modest. Carboplatin or cisplatin in conjunction with paclitaxel is the current first-line recommended chemotherapy for PSCP.

Adult↗
PubMed1998

Low-dose oral granisetron (1 mg) plus intravenous dexamethasone: efficacy in gynecologic cancer patients receiving carboplatin-based chemotherapy.

OBJECTIVE: The objective of this study was to determine the efficacy of a low-dose oral granisetron plus intravenous dexamethasone prophylactic antiemetic regimen in patients receiving carboplatin-based chemotherapy. PATIENTS AND METHODS: Patients with gynecologic malignancies being treated with either single-agent carboplatin or a carboplatin-paclitaxel regimen received a single 1-mg oral dose of granisetron 30 min prior to chemotherapy plus intravenous dexamethasone (20 mg) as prophylaxis for emesis. Patients either had not previously been treated with chemotherapy or had not received any cytotoxic drugs for >/=4 months prior to study entry. Effectiveness was evaluated based on the degree of control of nausea and vomiting during the 24 h following treatment. RESULTS: Of the 32 patients participating in this phase 2 trial, only 2 (6%) experienced any degree of nausea or vomiting within the first 24 h of chemotherapy administration. Both of these individuals had carcinomatosis and were experiencing emesis prior to chemotherapy. One patient developed mild delayed nausea >24 h after treatment. No major or minor toxic effects of the antiemetic regimen observed. CONCLUSION: A 1-mg dose of oral granisetron plus intravenous dexamethasone (20 mg) is a safe, effective, and relatively inexpensive prophylactic antiemetic regimen for patients receiving single-agent carboplatin or combination carboplatin-paclitaxel chemotherapy.

Adult↗