Phase II trial with Flavone Acetic Acid (NSC.347512, LM975) in patients with non-small cell lung cancer.
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Aged↗
Biomedical subjects
S B Kaye
Publications and source records attributed to S B Kaye.
5-Aza-2'-deoxycytidine (NSC 127716) in non-seminomatous testicular cancer. Phase II from the EORTC Early Clinical Trials Cooperative Group and Genito-Urinary Group.
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Adult↗
Phase II trials of fosquidone (GR63178A) in carcinoma of the breast, head and neck, ovary and melanoma.
A total of 91 eligible patients with metastatic cancer have been treated in a series of phase II trials of the novel pentacyclic pyrroloquinone, fosquidone. Tumour types were breast (24), ovary (25), head and neck (21) and melanoma (21). All patients, except those with melanoma had received prior chemotherapy. The drug was given intravenously as a 20 min infusion, at the dose of 120 mg/m2 on days 1 to 5 of a 3 week cycle. Treatment was well tolerated; the only significant side-effects being mild headaches and generalised musculo-skeletal pains. Response was assessed after 2 cycles of therapy. Only one patient (with head and neck cancer) achieved an objective partial response, lasting 6 weeks. A total of 12 patients demonstrated stable disease for a median duration of 15 to 20 weeks. Using this schedule of administration, fosquidone has no significant antitumour activity in this group of tumours.
Adult↗
High-dose epirubicin in chemotherapy refractory non-seminomatous germ cell cancer: a phase II study. EORTC Genito-Urinary Tract Cancer Co-operative Group. EORTC Early Clinical Trials Group.
Eighteen patients with progressive disseminated, platinum-resistant germ cell tumors were treated with epirubicin 135 mg/m2, every 3 weeks. One patient had stable disease, 17 developed progression. Myelosuppression was dose-limiting. One patient died of neutropenic septicemia. High-dose epirubicin is not active against platinum-resistant germ cell cancer.
Adolescent↗
Laboratory and phase I studies of new cancer drugs.
New drug discovery continues to follow the time-honored paths of screening and novel target identification combined with analogue development and serendipity. The agents selected here reflect these various approaches. They include drugs already showing significant antitumor activity, eg, anthrapyrazoles, temozolomide, camptothecin analogues, and taxotere, and updated information is provided on their development. Other drugs just entering or currently in phase I trials include rhizoxin, which seems capable of overcoming multidrug resistance; the novel bioreductive agent EO9 [corrected]; and bryostatin, a highly potent protein kinase C agonist. Sequence specificity could well prove to be an important factor in the development of DNA-interactive agents, and information is provided on the progress with distamycin mustard and the new cyclopropylpyrroloindole analogues carzelesin and adozelesin.
Antineoplastic Agents↗
Initial combination chemotherapy with cisplatin, methotrexate and vinblastine in locally advanced transitional cell carcinoma--response rate and pitfalls. MRC Subgroup in Advanced Bladder Cancer (on behalf of the MRC Urological Working Party).
A total of 51 patients with locally advanced transitional cell carcinoma of the bladder were entered into a phase II study to evaluate the effect of initial cisplatin (100 mg/m2, Day 2) combined with methotrexate (30 mg/m2, Days 1 and 8) and vinblastine (4 mg/m2, Days 1 and 8). Of 44 evaluable patients, 25 (57%) achieved an objective response of their primary bladder tumour (complete response (CR): 4 patients; partial response (PR): 21 patients); 30 of the 36 patients with micturition disturbances obtained relief. Toxicity was acceptable, but dose modifications due to haematological or renal toxicity were required in 153 of the 690 drug courses. Non-protocol dose modifications were performed 45 times. The experience gained in this trial emphasises the need for improved co-operation between urologists, radiologists and clinical oncologists in such multicentre phase II studies. Difficulties were observed in adhering to dose modification rules, assessing pre-treatment tumour size (due to variation in quality of measure and in timing relative to initial transurethral resection (TUR)) and defining response to chemotherapy (due to failure to perform mandatory investigations at the right time). This study also illustrates that the accepted criteria for assessing response in the primary bladder tumour are difficult to apply in practice and that the results of any study using this indicator lesion require caution in their interpretation.
Aged↗
Dependence of ocular protrusion, asymmetry of protrusion and lateral interobital width on age.
Ocular protrusion and lateral interorbital width were measured in 462 patients; 187 females and 275 males ranging in age from 9 to 92 years. The object of this study was to determine if ocular protrusion, asymmetry of protrusion and lateral interorbital width was dependent upon age. There was a significant reduction in ocular protrusion and lateral interorbital width with increasing age in both females and males. There was a strong correlation between ocular protrusion and lateral interorbital width. Asymmetry of ocular protrusion did not develop with age. These findings may help in the longitudinal assessment of patients.
Adolescent↗
A method for assessing the accuracy of surgical technique in the correction of astigmatism.
Surgical results can be assessed as a function of what was aimed for, what was done, and what was achieved. One of the aims of refractive surgery is to reduce astigmatism; the smaller the postoperative astigmatism the better the result. Determination of what was done--that is, the surgical effect, can be calculated from the preoperative and postoperative astigmatism. A simplified formulation is described which facilitates the calculation (magnitude and direction) of this surgical effect. In addition, an expression for surgical accuracy is described, as a function of what was aimed for and what was achieved.
Astigmatism↗
Non-traumatic acquisition of herpes simplex virus infection through the eye.
Primary ocular herpes is usually seen as a follicular conjunctivitis and blepharitis, with or without involvement of the cornea. It is unknown, however, to what extent asymptomatic and/or subclinical primary disease occurs, and whether primary ocular herpes follows direct droplet spread to the eye. Previous models of murine ocular herpes have used trauma (scarification) to introduce virus into the cornea, producing disease which results in significant corneal scarring. To mimic a likely route of infection in humans, a droplet containing virus was placed on the mouse eye and clinical disease recorded. At least 1 month after inoculation, serum was assayed for neutralising antibodies and the cornea, iris, and trigeminal ganglion were investigated for evidence of herpes simplex virus type 1, by cocultivation and the polymerase chain reaction. Some animals showed a severe ulcerative blepharitis with little to no involvement of the cornea, while disease was undetectable in others. The development of disease depended on the dose and strain of virus and age of the animal, with older mice appearing more resistant. Virus was isolated from the trigeminal ganglion of younger animals inoculated with higher doses of virus, after 21 days in culture, suggesting that latency had been established. Neutralising antibodies were present in most mice irrespective of the presence of recognisable clinical disease. Using primers for the thymidine kinase and glycoprotein C regions of the viral genome, herpes simplex virus type 1 DNA was found in the cornea, iris, and trigeminal ganglion of most animals and showed a good correlation with the presence of neutralising antibodies. It would thus appear that herpes simplex virus type 1 is able to accede into the cornea, iris, and trigeminal ganglion following nontraumatic application of virus onto the mouse eye. This model mimics primary ocular disease in humans and may be useful for studies on recurrent disease and the spread of ocular herpes.
Animals↗
The Second Medical Research Council study of prognostic factors in nonseminomatous germ cell tumors. Medical Research Council Testicular Tumour Working Party.
PURPOSE: To assess prognostic factors in a large population of patients with metastatic nonseminomatous germ cell tumors (NSGCT) arising in gonadal or extragonadal sites. PATIENTS AND METHODS: Data from 795 patients treated with chemotherapy between 1982 and 1986 in 13 centers were analyzed. Particular emphasis was placed on exact tumor measurements (eg, size of nodal masses, number of lung metastases), and the diagnostic pathology was also reviewed. Cox regression analysis was performed on these data. The patients were treated with a variety of cisplatin-containing chemotherapy regimens, 86% of which included etoposide. RESULTS: With median follow-up of 45 months, overall 3-year survival is 85%. The independently adverse features proved to be (1) the presence of liver, bone, or brain metastases; (2) raised marker levels (alpha-fetoprotein [AFP] level greater than 1,000 kU/L or beta subunit of human chorionic gonadotropin [HCG] greater than 10,000 IU/L [corrected]); (3) the presence of a mediastinal mass greater than 5 cm in diameter; (4) the presence of 20 or more lung metastases; (5) increasing age; and (6) absence of undifferentiated teratoma (embryonal carcinoma) or fibrous tissue from the primary tumor. CONCLUSIONS: The first four factors were used to define a simple prognostic classification. A good-prognosis group having none of these features comprised 67% of our patient population and had a 3-year survival of 93%. The remaining 33% of patients having at least one of these features had a 3-year survival rate of 68%. These patient groups are currently the subjects of international randomized clinical trials.
Adult↗
Medical Research Council prospective study of surveillance for stage I testicular teratoma. Medical Research Council Testicular Tumors Working Party.
PURPOSE: A prospective study of surveillance after orchidectomy alone in patients with stage I nonseminomatous germ cell testicular tumor (NSGCT) was performed to determine the relapse-free rate and to identify the histologic criteria that predict for relapse. PATIENTS AND METHODS: Three hundred ninety-six patients from 16 United Kingdom and one Norwegian centers were entered onto the study between January 1, 1984 and October 1, 1987 of whom 373 were eligible for analysis. In a previous retrospective study, we defined a prognostic index based on histologic criteria that identified a group of patients with a high risk of relapse. This index was based on the presence of venous and lymphatic invasion, undifferentiated cells, and the absence of yolk sac elements in the primary tumor. RESULTS: The 2-year actuarial relapse-free rate after orchidectomy was 75% (95% confidence interval, 71% to 79%), and the rate at 5 years was 73%. Five patients died of tumor or treatment-related complications, which resulted in a 5-year survival of 98%. The relapse-free rate in patients with three or four risk factors was 54%. CONCLUSIONS: This study confirms the safety of surveillance as a method of management and identifies a group of patients with a high risk of relapse. A prospective phase II study has been initiated to determine whether two courses of platinum-based adjuvant chemotherapy will prevent relapse in these high-risk patients.
Adult↗
So, what is a clinical oncologist?
The non-surgical management of patients with cancer often involves both radiation and medical oncologists. It is argued here that the term 'clinical oncologist' should encompass both specialties, but implicit in this is agreement in matters of both joint training and the delivery of treatment in integrated cancer centres. The provision of optimal care in district general hospitals as well as cancer centres also depends on a proper structure to which clinical oncologists provide the key. The newly created Joint Council on Oncology (involving representatives of the Royal Colleges of Physicians and Radiologists) should facilitate these agreements, breaking down old prejudices and helping to create a better standard of treatment for cancer patients in Britain.
Cancer Care Facilities↗
Comparison of dexamethasone and ondansetron in the prophylaxis of emesis induced by moderately emetogenic chemotherapy.
A multicentre, randomised, double-blind, cross-over trial was done to compare the efficacy and safety of a serotonin receptor antagonist--ondansetron--and dexamethasone in the prophylaxis of acute and delayed emesis and nausea induced by moderately emetogenic non-platinum-containing chemotherapy regimens. Patients were treated as outpatients and received intravenous ondansetron 4 mg or dexamethasone 8 mg before chemotherapy and oral maintenance (ondansetron 4 mg every 6 h and dexamethasone reducing from 4 mg to 1 mg 6-hourly between days 1 and 5) for 5 days. 112 patients were treated (38 men, 73 women, 1 with no gender recorded; age range 30-73 years) and 100 were evaluable for cross-over analysis. Patients taking ondansetron or dexamethasone reported no significant difference in complete and major control of acute (83% vs 79%, p = 0.46) or delayed (82% vs 88%, p = 0.214) emesis (vomiting plus retches). Significantly more patients on dexamethasone (87%) than on ondansetron (72%) reported control of delayed nausea (days 2-5) (p = 0.003). Both drugs were well tolerated with no significant difference in the number of adverse events, and this is reflected by similar patient preference for ondansetron (40%) and dexamethasone (30%) (p = 0.244). Both drugs offer adequate out-patient control of chemotherapy-induced emesis; however, dexamethasone has an advantage in the control of delayed nausea, and also in terms of cost and resource allocation.
Acute Disease↗
Medical audit, cancer registration, and survival in ovarian cancer.
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Actuarial Analysis↗
Phase I study of the anthrapyrazole biantrazole: clinical results and pharmacology.
In a phase I study the anthrapyrazole biantrazole (Warner-Lambert Company) was given to 41 patients with tumour refractory to existing therapy. The drug was given i.v. weekly for 3 weeks, with a 3-week interval between courses. At the 1st week a full pharmacokinetic study was performed, and at weeks 2 and 3, blood samples were taken at 1 and 6 h following treatment to check for drug accumulation. Biantrazole pharmacokinetics were linear with respect to the AUC (r = 0.924) over the full range of doses studied (4-36 mg/m2) but exhibited large inter-patient variations at each dose level. Elimination was triphasic, comprising two rapid early phases and a long terminal half-life (mean, 14.1 +/- 7.8 h). There was no evidence of drug accumulation over the 3-week treatment period. Approximately 12% of the parent drug was excreted unchanged in the urine together with two non-circulating, more water-soluble metabolites. Biantrazole was well tolerated but did cause moderate emesis at doses of greater than 18 mg/m2 and mild alopecia. The dose-limiting side effect was leucopenia, with no other major toxicity being observed. One patient developed biventricular failure that was not clearly related to biantrazole administration. On the present schedule, the recommended dose of biantrazole is 24 mg/m2. No response were seen in this patient population.
Adolescent↗
Malignant pineal teratomas: a report on three patients and the case for craniospinal irradiation following chemotherapy.
Malignant pineal teratomas carry a poor prognosis. We describe a long-term survivor after chemotherapy and craniospinal irradiation, and another who achieved only transient disease control with chemotherapy and cranial irradiation. Spinal cord spread occurred in first patient and long-term survivors have been reported following surgery and craniospinal irradiation alone, suggesting a role for craniospinal irradiation following chemotherapy.
Adolescent↗
Multidrug resistance: clinical relevance in haematological malignancies.
Multidrug resistance describes an experimental observation which appears to explain cross-resistance to certain structurally unrelated cytotoxic agents, including anthracyclines, vinca alkaloids and podophyllotoxins. It is now clear that a major factor responsible for its development is increased expression of a membrane glycoprotein--P-glycoprotein, which functions as an energy-dependent efflux pump. Recent data, particularly in haematological malignancies such as acute non-lymphocytic leukaemia, myeloma and non-Hodgkin's lymphoma, indicate that P-glycoprotein may be involved in the development of clinical drug resistance. The potential therefore exists for new therapeutic studies aimed at circumventing resistance which develops through this mechanism, by using modulators, such as verapamil, quinidine and several others, which prevent cellular drug efflux by competitive binding to P-glycoprotein.
ATP Binding Cassette Transporter, Subfamily B, Mem↗
Circumvention of pleiotropic drug resistance in subcutaneous tumours in vivo with verapamil and clomipramine.
The development of pleiotropic drug resistance (PDR) in vivo in solid tumour models suggests that a similar process may occur in the clinic. A subline of the Ridgway osteogenic sarcoma (ROS)--a murine subcutaneously-growing solid tumour--with moderate resistance (1.5 fold) to actinomycin D was selected by repeated suboptimal treatment with this drug in vivo. This subline (ROS/ADX/G2) showed cross-resistance to vincristine (3.5 fold) and etoposide (over 5.1 fold) but not to doxorubicin. The resistance could in all cases be partly or completely overcome by treatment with non-cytotoxic doses of verapamil or clomipramine. Resistance to actinomycin in this model was associated with lower (up to 3.2 fold) drug accumulation into tumours which could be increased (up to 2.8 fold) by treatment with 25 micrograms/g verapamil. These data support clinical trials of the use of membrane-active agents to overcome PDR.
Animals↗