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Biomedical subjects

J R Clark

Publications and source records attributed to J R Clark.

At least 55 records · Page 3Linked to original sources
PubMed1992

Continuous-infusion cisplatin, 5-fluorouracil, and bolus methotrexate in the treatment of advanced non-small cell lung cancer.

BACKGROUND: Cisplatin and 5-fluorouracil have noted synergy in preclinical systems. The authors combined methotrexate with infusional cisplatin and 5-fluorouracil in an attempt to produce a regimen with improved activity in advanced NSCLC: METHODS: Twenty-six ambulatory patients with previously untreated non-small cell lung cancer were treated with continuous-infusion cisplatin (25 mg/m2/day for 5 days), 5-fluorouracil (800 mg/m2/day for 5 days), and intermediate-dose methotrexate (200 mg/m2 on days 15, 22), followed by leucovorin rescue (PFM regimen). RESULTS: Patients received a median of four cycles of therapy. Two patients had a complete response, and 10 had a partial response (overall response rate, 46.2% or 12 of 26). The median time to treatment failure was 22.5 weeks; the median survival was 55 weeks from the start of chemotherapy. There were no toxic deaths attributed to chemotherapy. Thrombocytopenia was the only Grade 4 toxicity (27%). Grade 1/4 and 2/4 peripheral neuropathy occurred in 17 of 26 patients (66%) and was associated with a cumulative cisplatin dose of more than 300 mg/m2. CONCLUSIONS: PFM (using continuous-infusion cisplatin) produced a high response rate but resulted in an high incidence of low-grade peripheral neuropathy.

Adult↗
PubMed1991

Analysis of prognostic factors in squamous cell carcinomas of the head and neck.

It appears that prognostic factors of proven value in the management of other malignancies have marginal value in the treatment of patients with squamous cell carcinomas of the head and neck (SCCHN). For example, age, sex, and performance status do not correlate with treatment outcome. Similarly, histologic differentiation has little predictive value, with undifferentiated carcinomas of nasopharyngeal origin being a possible exception. On the other hand, primary tumor site may be an important prognostic factor, with tumors arising from the nasopharynx, oral cavity, and possibly the oropharynx having a more favorable outcome, whereas tumors of the hypopharynx appear to be the least favorable. A tumor's TNM stage is also highly predictive of response to treatment and survival. Overall stage of disease is an effective predictor of relapse and survival only for patients with limited disease and only after the primary site is specified. Independent of primary tumor site, an inverse correlation clearly exists between T and N stage and either response to treatment or overall survival. Flow cytometry, a relatively new test, appears to be one of the most significant predictors of response to chemotherapy, relapse, and survival in patients with SCCHN. As a prognostic factor, DNA tumor content may be independent of all other known clinical and pathologic factors. Patients with diploid tumors have a superior relapse-free and overall survival as compared with patients whose tumors are aneuploid. Another parameter of significant value is the patient's response to induction chemotherapy, with responding patients demonstrating a far superior relapse-free and overall survival compared with nonresponders. In summary, the site of the primary tumor, its T stage, N stage, and DNA content, and the magnitude of its response to induction chemotherapy are the most valuable prognostic factors in SCCHN. It is assumed, however, that as new and more effective therapies are developed for patients with SCCHN, previously significant prognostic factors will cease to have clinical or scientific value. Similarly, as new diagnostic tests and staging tools are developed, a new generation of prognostic factors with greater biologic and clinical relevance is likely to emerge. In the evolution of new therapies for patients with SCCHN, prognostic factors such as those mentioned here or ones yet to be evaluated will be central to the design of clinical studies and the identification of specific patients for specific therapies. Once treatment is initiated, treatment-related prognostic factors may further identify patients for whom modifications of the initial therapeutic plan would be appropriate.(ABSTRACT TRUNCATED AT 400 WORDS)

Adult↗
PubMed1991

The role of cisplatin in treatment regimens for squamous cell carcinoma of the head and neck.

Advanced squamous cell carcinoma of the head and neck (SCCHN) is both a local-regional and a systemic disease that is ineffectively managed by conventional surgery and radiotherapy. For patients with advanced but potentially curable (Mo) disease, the morbidity associated with conventional surgery or radiotherapy may be significant whereas the probability of lasting disease control is low. For those with recurrent or metastatic lesions, surgery or radiotherapy are rarely effective options. In this setting, chemotherapy has been evaluated as primary therapy for patients with recurrent or metastatic disease and as an adjunct to surgery or radiotherapy for those with potentially curable lesions. As palliative therapy, methotrexate remains the single agent of choice. Combination chemotherapy has been associated with a higher response rate but not improved survival when compared with methotrexate alone. Cisplatin, both as a single agent and in combination with 5-fluorouracil, is active against SCCHN, and may be superior to methotrexate in antitumor activity. The impact of induction and adjuvant chemotherapy or concurrent chemotherapy and radiotherapy in patients with potentially curable lesions remains controversial. A specific role for chemotherapy has not been confirmed by prospective randomized trial, but effective therapies have been achieved: Regimens with increased activity against squamous carcinomas have been reported, clinical trials with sufficient power to reach significant conclusions have been published, and organ preservation has been confirmed as an appropriate end point for studies of induction chemotherapy or concurrent chemotherapy and radiation. The clinical experience with chemotherapy for patients with recurrent or metastatic SCCHN as well as induction and adjuvant chemotherapy and concurrent chemotherapy and radiotherapy for those with potentially curable disease is reviewed, with particular emphasis given to trials involving cisplatin and to avenues for continued clinical investigation.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1990

Continuous infusion high-dose leucovorin with 5-fluorouracil and cisplatin for untreated stage IV carcinoma of the head and neck.

STUDY OBJECTIVE: To study the activity of continuous infusion cisplatin, 5-fluorouracil, and high-dose leucovorin (PFL) as induction chemotherapy in patients with previously untreated, advanced squamous cell carcinoma of the head and neck. DESIGN: Nonrandomized, prospective trial. SETTING: A comprehensive cancer center. PATIENTS: Thirty-five patients (4 patients [11%], stage III; 31 patients [89%], stage IV [MO]), all evaluable for response and toxicity. INTERVENTIONS: Two to three cycles of PFL before definitive, local-regional therapy (surgery and radiation therapy or radiation therapy alone). Chemotherapy included continuous intravenous infusion of cisplatin (25 mg/m2 body surface area daily, days 1 through 5); 5-fluorouracil (800 mg/m2 body surface area daily, days 2 through 6); and leucovorin (500 mg/m2 body surface area daily, days 1 through 6) administered once every 28 days. Pathologic response was evaluated by surgical resection or biopsy. Serum-reduced folates were measured before and 18 hours after the initiation of chemotherapy. RESULTS: A clinical response to PFL was achieved in 28 of 35 (80%) patients: 23 (66%) patients had a complete response (90% CI, 50% to 79%) and 5 (14%) patients, a partial response. A complete response was confirmed pathologically in 14 of 19 (74%) patients. The most common toxicity was mucositis (grade 2 to 3; 94% of patients). Dose reduction for toxicity was necessary in 11 (31%) patients. There were no treatment-related deaths. Serum levels of leucovorin and (6S)5-methyltetrahydrofolate were measured in 7 patients. After 18 hours, the mean leucovorin level (+/- SD) was 34.3 +/- 1.5 mumol/L, of which only 8.0 +/- 0.5% was the active 6S isomer. The mean serum (6S)5-methyltetrahydrofolate was 9.2 +/- 0.6 mumol/L. CONCLUSIONS: Continuous infusion cisplatin, 5-fluorouracil, and high-dose leucovorin is a new and highly active chemotherapy regimen that can achieve clinical and pathologically confirmed complete responses in a substantial proportion of patients with advanced, local-regional squamous cell carcinoma of the head and neck. Further studies are needed to confirm the activity of PFL and to determine its potential impact on local tumor control and disease-free and overall survival.

Adult↗
PubMed1990

Surgery for pulmonary metastases from renal cell carcinoma. Army experience from 1977-1987.

The Army Medical Centers' combined ten-year experience (1977-1987) with renal cell carcinoma metastatic to the lung is presented. Those patients who underwent resection of the lung metastases were compared with those who did not. Certain factors within the two groups were analyzed mainly for effect on survival: number and location of pulmonary metastases, disease-free interval from nephrectomy, extent of lung resection, and synchronous vs asynchronous metastases. Comparisons were made with reports from the literature, and conclusions were made in reference to indications for resection and other modes of therapy.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1990

Detection of B- and T-cells in paraffin-embedded tissue sections. Diagnostic utility of commercially obtained 4KB5 and UCHL-1.

Although many recent studies have begun exploring the diagnostic utility of anti-B- and anti-T-cell antibodies that work on paraffin-embedded tissue sections, the most optimal panel to use remains uncertain. In addition, many of the published reports have used antibodies obtained before their commercial formulation and distribution. For these reasons, B5-fixed paraffin-embedded tissue samples from 174 reactive or neoplastic lymphoid and hematopoietic proliferations were immunostained with the commercially obtained antibodies 4KB5, UCHL-1, and, in selected cases, L26. In reactive nodes, 4KB5 stained B-cell areas and UCHL-1 T-cell areas. Seventy-nine percent of the B-cell neoplasms were 4KB5 positive, and only 2% were UCHL-1 positive. Two cases of myeloma were 4KB5 and UCHL-1 negative. The 4KB5-negative B-cell lymphomas (ML-B) were all L-26 positive. UCHL-1 stained 78% of the T-cell lymphomas (ML-T), and 4KB5 stained 14%. In the five 4KB5-positive putative T-cell lymphomas, immunoglobulin and T-cell receptor gene rearrangement studies were performed. In Hodgkin's disease (HD), Reed-Sternberg (RS) cells were UCHL-1 negative in 75% of cases and occasionally positive in 25%. Definite 4KB5 positivity of RS cells was identified in both cases of lymphocyte predominant HD and in one case of nodular sclerosing HD with monomorphic large cell areas. With the exception of 1 of 15 acute nonlymphocytic leukemias that was UCHL-1 positive, all acute leukemias were 4KB5 and UCHL-1 negative. In summary, commercially obtained 4KB5 and UCHL-1 form a useful but not absolutely specific or sensitive paraffin section immunoperoxidase panel for the categorization of B- and T-cell lymphoid neoplasms. Addition of L26 appears to add to the sensitivity and specificity of the panel. Definite immunophenotypic distinction of HD from non-Hodgkin's lymphomas, particularly of T-cell type, often was not possible.

Antibodies, Monoclonal↗
PubMed1990

Oral complications following neoadjuvant chemotherapy in patients with head and neck cancer.

Oral complications from cancer chemotherapy are well documented for the hematologic malignancies but are less well defined for cancers of the head and neck. This prospective study examined 82 patients with stage III or IV disease to determine the incidence and severity of oral sequelae following a total of 141 cycles of neoadjuvant chemotherapy. Taste alteration (37%) was the most frequent problem, followed by mucositis (30%) and ulceration (22%). Xerostomia, increased salivary flow, loss of appetite, weight loss, dysphagia, bleeding, and infection were also encountered. We conclude that oral problems are common following chemotherapy for head and neck tumors and that more aggressive investigational protocols will result in a much higher incidence and severity of problems. Prevention of these sequelae by conventional as well as investigational means is important to keep them from becoming dose-limiting problems.

Antineoplastic Agents↗
PubMed1989

A phase I-II trial of cisplatin, hyperthermia and radiation in patients with locally advanced malignancies.

A Phase I-II trial testing the addition of systemic cisplatin (CDDP) to local hyperthermia and radiation was conducted to determine the dose of cisplatin that is tolerable once weekly for 6 weeks and to estimate the therapeutic potential of this trimodality combination in patients with locally advanced malignancies. Cisplatin at 20 mg/m2 (4 patients), 30 mg/m2 (8 patients), and 40 mg/m2 (12 patients) was given rapidly (over 5-10 min) i.v. after prehydration with 1 liter of normal saline. After approximately two-thirds of the cisplatin dose had been delivered, microwave hyperthermia was begun and continued for 60 min; the target minimum tumor temperature was 43 degrees C. Following hyperthermia, a 400 cGy fraction of radiation was delivered to the tumor. On other days during the treatment weeks, additional 200 cGy fractions were given to total doses of 6,000-6600 cGy in patients with full radiation tolerance or 2400-3600 cGy in patients with limited radiation tolerance. The 24 patients in this trial had a median age of 57 years and the predominant sites/tumor types were head and neck/squamous cell carcinoma (9) and chest wall/breast adenocarcinoma (9). Seventeen of the 24 treated tumors (70%) had previously been irradiated. Eighteen patients (75%) had received prior chemotherapy and nine patients (38%) had previously been treated with cisplatin. Bone marrow suppression was dose limiting in patients heavily pretreated with chemotherapy and chest wall radiation. No significant toxicities were observed at the 20 and 30 mg/m2 dose levels, but 5 of the 12 patients (42%) treated at 40 mg/m2 required modification of the cisplatin dose because of blood count suppression in four patients and mild renal dysfunction in one patient. Each of the patients with bone marrow suppression, however, had been heavily pretreated except for one patient with thrombocytopenia due to hypersplenism. Nausea and vomiting were mild with use of a standard, multiagent antiemetic regimen. Twelve patients (50%) attained a complete regression (CR) and 12 patients (50%) a partial regression (PR). Complete regression appeared to correlate with small tumor volumes (115 cc for CR versus 199 cc for PR patients) and higher tumor temperatures (4.6 average minimum equivalent minutes at 43 degrees C in CR versus 2.0 min in PR patients). Local toxicities included second degree burns in 12 patients (50%) and third degree burns in 6 (25%), but all burns healed in 4-12 weeks without surgical intervention.(ABSTRACT TRUNCATED AT 400 WORDS)

Adult↗
PubMed1989

Abdominal aortic aneurysm repair in patients with pelvic kidney. Technical considerations and literature review.

Effective methods for performing abdominal aortic aneurysmectomy associated with congenital pelvic kidney are presented. The embryology and surgical anatomy of these lesions are reviewed. Ordinarily, successful aortic reconstruction can be performed with low risk to the pelvic kidney by use of readily available in situ cold perfusion. Two illustrative case reports applying this method are presented. The recently reported technique of double proximal clamping of the aorta was also employed in one case. This technique allows lumbar collaterals within the aneurysm to perfuse the kidney during construction of the proximal aortic anastomosis, thereby minimizing absolute renal ischemic time. Both in situ cold perfusion and double proximal clamping are effective methods for renal preservation that do not rely on complex extraanatomic techniques. A review of the literature with a discussion of the advantages and disadvantages of previously reported methods of renal preservation is presented.

Aged↗
PubMed1989

Chemotherapy for head and neck cancer: progress and controversy in the management of patients with M0 disease.

The overall survival of patients with advanced squamous cell carcinoma of the head and neck (SCCHN) has not changed despite recent advances in surgical and radiotherapeutic techniques. For most patients with advanced disease, the morbidity associated with conventional surgery or radiotherapy is unacceptably high while the probability of locoregional and distant control of disease is low. The use of chemotherapy with surgery or radiotherapy for patients with SCCHN remains a controversial but highly promising treatment that attempts to improve locoregional control and overall survival or facilitate reductions in the locoregional treatment required for control of disease. Since the early 1960s, numerous trials have evaluated the impact of induction and adjuvant chemotherapy or concurrent chemotherapy and radiotherapy in the management of patients with advanced, but potentially curable, (M0) lesions. While a specific role for chemotherapy in the treatment of patients with SCCHN has not been confirmed by prospective randomized trials, considerable progress in the development of effective therapies has been achieved recently. This progress is characterized by the definition of chemotherapy with increased activity against squamous cell carcinomas and the organization of clinical trials with sufficient power to reach significant conclusions. This article reviews the experience with induction and adjuvant chemotherapy and concurrent chemotherapy and radiotherapy in the multidisciplinary treatment of patients with advanced SCCHN. The potential advantages as well as clinical experience with chemotherapy in these settings are presented.

Antineoplastic Agents↗
PubMed1988

Pattern of ovarian progesterone secretion during the luteal phase of the ovine estrous cycle.

Pulsatile secretion of progesterone has been observed during the late luteal phase of the menstrual cycle in the rhesus monkey and human. As the luteal phase progresses in each of these species, there is a pattern of decreased frequency and increased amplitude of progesterone pulses. The present study was designed to determine the pattern of progesterone secretion during the late luteal phase (Days 10-16) of the normal ovine estrous cycle. Five unanesthetized ewes, each bearing an indwelling cannula in the utero-ovarian vein, were bled every 15 min from 0800 h on Day 10 through 0800 h on Day 16 of the estrous cycle. With the computer program PULSAR, it was determined that progesterone secretion was episodic, with pulsations observed on all days. Analysis of variance was used to determine differences in frequency, amplitude, and interpeak interval (IPI) of progesterone pulses among ewes and days. The ewes averaged 8.0 +/- 0.63 pulses of progesterone per 24 h. Mean frequency of pulses was not different between days but showed differences between ewes. Mean amplitude of progesterone pulses was 7.0 +/- 0.27 ng/ml, with no differences observed either between days or between ewes. Mean IPI was 197 +/- 7.1 min, and, like frequency, the IPI was not different between days, but varied between ewes. No consistent temporal relationship was found between progesterone pulses and luteinizing hormone (LH), as determined by bioassay and radioimmunoassay, on Day 14 of the cycle in one ewe. The results indicate that progesterone secretion is episodic during the luteal phase of the ovine estrous cycle and is independent of LH pulses.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1988

Arthroscopic meniscus repair with a posterior incision.

The transarticular arthroscopic approach with a posterior incision provided a method of repairing more than 98% of unstable meniscus tears encountered between November 1983 and November 1986. A clinically stable bond was obtained in most of these tears with a subjective failure rate of 2% or less. There was a trend towards better healing of isolated meniscus repairs and lateral meniscus tears less than eight weeks old associated with ACL reconstruction when a blood clot injection was used to supplement the rasp abrasion of the parameniscal synovium. Healing of rim widths to 5 mm can be obtained with these methods. Indications for meniscus repair include all lateral meniscus tears and all medial meniscus tears except when repair of a stump would not replace 25% or more of the missing area. In our experience, this includes more than 98% of all unstable meniscus tears. Contraindications to meniscus repair include short (10 mm or less) stable tears, partial thickness (less than 50% of vertical height), and shallow radial tears (3 mm or less in depth). The posterior incision and popliteal retractor are necessary to protect the popliteal neurovascular structures.

Adolescent↗
PubMed1988

Angiokeratoma of the vulva. A case report.

Angiokeratoma of the vulva is a rarely reported, benign condition that usually presents as one or a few isolated, 2- to 3-mm papules on the vulva. This case represents an extensive lesion that was managed surgically. Such extensive disease and its treatment have not been described before in detail in the literature.

Angiokeratoma↗
PubMed1988

Chemotherapeutic strategies in the multidisciplinary treatment of head and neck cancer.

A role for chemotherapy in the multidisciplinary treatment of patients with advanced squamous cell carcinoma of the head and neck (SCCHN) is yet to be defined. Results of uncontrolled studies indicate high response rates to induction chemotherapy and an association between a response to chemotherapy and either local-regional control or survival. Unfortunately, results of randomized, controlled trials have not confirmed an overall survival advantage with such treatment. From 1979 to the present, the Dana-Farber Cancer Institute has registered more than 224 patients on two trials of induction and adjuvant chemotherapy for patients with stage III to IV SCCHN. Protocol 80-016 (1979 to 1983) evaluated two cycles of induction cisplatin, bleomycin, and methotrexate/leucovorin (PBM) before local regional treatment in 114 patients. Eighty-nine (78%) patients responded to PBM, with 30 (28%) patients achieving a complete response (CR). After surgery and/or radiotherapy (RT), 46 responders to induction PBM entered a trial of the randomly assigned additional adjuvant PBM. Protocol 83-084 (1983 to present) randomly assigned patients to receive up to four cycles of either induction PBM or cisplatin and infusion 5-fluorouracil before local treatment. Adjuvant chemotherapy was not used in the latter study. Updated results from both trials will be presented, with their implications for future phase II and III multidisciplinary studies. Optimal approaches to the treatment of patients with advanced SCCHN can include planned reductions in the extent of surgery or RT offered to selected patients with a good response to induction chemotherapy but may require adjuvant chemotherapy for patients at high risk for recurrent disease. Until the rate of CR to induction chemotherapy is reproducibly over 50%, documentation of an improved overall survival with multidisciplinary treatment may be difficult.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1987

Cyclophosphamide, doxorubicin, and cisplatin combination chemotherapy for advanced carcinomas of salivary gland origin.

Thirteen patients with carcinomas of major and minor salivary gland origin (nine adenoid cystic carcinomas and four adenocarcinomas) were treated with cyclophosphamide (500 mg/m2), doxorubicin (50 mg/m2), and cisplatin (50 mg/m2) (CAP) by intravenous injections on the first day of a 28-day regimen. Sixty-one cycles of CAP were administered (mean, 4.7 cycles per patient). Eleven patients were treated for palliation of recurrent disease (locoregional, ten; lung, ten; liver, three; and bone, three). Two patients untreated previously, one with extensive local disease involving the base of the skull and one with a solitary lung metastasis (resected with a positive margin) and an initially unappreciated base of tongue primary, received two cycles of CAP followed by local treatment and adjuvant CAP. Previous therapy for the 11 patients with recurrent disease included surgery (ten), radiotherapy [RT(11)], chemotherapy (three), or hormonal therapy (two). Three complete and three partial responses to chemotherapy were noted for an overall response rate of 46%. The median duration of response in palliative patients was 5 months (range, 2 to 9). Of the two patients receiving induction CAP, one relapsed with distant disease 26 months after treatment, and the other remains disease-free after 60 months of follow-up examination. Chemotherapy was well tolerated generally, and no chemotherapy-related deaths occurred. One hypertensive patient suffered a stroke after 3 cycles of therapy. CAP is an active regimen against salivary gland carcinomas and deserves further study. Also, it may be of value as induction or adjuvant treatment for patients with advanced disease untreated previously.

Adenocarcinoma↗