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Biomedical subjects

T E Moon

Publications and source records attributed to T E Moon.

At least 73 records · Page 4Linked to original sources
PubMed1981

Chemotherapy of ovarian cancer directed by the human tumor stem cell assay.

The human tumor stem cell assay (HTSCA) has been used to study the in vitro sensitivity rates of anticancer drugs used in the treatment of 115 patients with previously untreated and relapsing ovarian cancer. The data from these studies have identified patterns of cross resistance and residual sensitivity between these agents, and have allowed the prospective selection of single agents possessing in vitro activity for the treatment of 32 patients with relapsing disease. cis-Platinum and vinblastine were the most active agents in vitro against ovarian TCFUs from both previously untreated and relapsing patients. Prior therapy with even one drug was associated with the acquisition of resistance to several classes of compounds (e.g., melphalan resistance was almost always associated with in vitro adriamycin resistance, P less than 0.001). A clinical trial yielding similar data would have required nearly 450 evaluable ovarian cancer patients. In 11 of 32 patients in vitro testing predicted sensitivity to single agents: eight of these had partial remissions for a predictive accuracy of 73%. In 33 instances the HTSCA had 100% accuracy in predicting the lack of clinical response. Thus, the HTSCA for advanced ovarian cancer appears to have a similar predictive accuracy rate to the estrogen receptor assay for predicting the response to hormonal therapy for disseminated breast cancer.

Antineoplastic Agents↗
PubMed1981

Quantitation of drug sensitivity by human metastatic melanoma colony-forming units.

We measured the effect of 6 standard (Adriamycin, BCNU, DTIC, melphalan, vinblastine, actinomycin D) and 3 Phase II agents (cis-platinum, vindesine, AMSA) on melanoma colony-forming units (CFU) in soft agar from biopsies of 50 patients with metastatic melanoma. Melanoma CFU demonstrated marked heterogeneity in chemosensitivity to these 9 drugs. Reduction in survival of CFU below 38% at one-tenth the pharmacologically achievable 1h concentration (our operational definition of chemosensitivity) was obtained in only 19% of 200 in vitro trials, and was usually the same whether or not patients had been exposed to prior chemotherapy, suggesting that melanoma CFU are inherently resistant to presently available chemotherapeutic drugs. The soft-agar assay was 86% accurate (25/29 cases) in identifying drugs to which the tumour was resistant in vivo, and 63% accurate (12/19 trials) in identifying drugs to which the tumour was clinically sensitive, counting mixed responses as responses. In contrast, if mixed responses were classified as progressive disease, the accuracy of identification of sensitivity fell to 42% (8/19 trials). These investigations furnish a quantitative description of the chemosensitivity of human metastatic melanoma CFU. Additionally, these studies serve as a useful step towards the development of an in vitro chemosensitivity test for human melanoma, and provide an operational quantitative basis for further exploration of in vitro-directed therapy in metastatic neoplasms.

Antineoplastic Agents↗
PubMed1980

Prediction of outcome in metastatic breast cancer treated with adriamycin combination chemotherapy.

Univariate and multivariate regression methods were used to analyze 17 potential clinical prognostic factors among 138 patients with advanced breast cancer who received Adriamycin-cyclophosphamide combination chemotherapy between 1973 and 1977 at the University of Arizona. Follow-up of patients was through September 1979, and survival data were nearly complete. Different factors varied in the relationship to outcome, but age, treatment, and response were important. Selecting the three most strongly related factors, predictive regression equations were developed, which described three types of possible outcome: 1) objective response (age, treatment, and liver involvement), 2) freedom from relapse (age, lung involvement, and response), and 3) survival (age, the number of involved sites [less than or equal to 2 or > 2], and treatment). Since use of the regression equations is cumbersome for clinical practice, three simplified tables were constructed to readily predict response, duration of response, and survival before the initiation of treatment.

Adult↗
PubMed1980

In-vitro clonogenic assay for predicting response of ovarian cancer to chemotherapy.

95 clinical trials of anticancer drugs were done in 40 patients with advanced ovarian cancer who had undergone an in-vitro soft-agar human tumour stem-cell assay for drug sensitivity. In the 95 clinical trials, 13 of 21 patients responded clinically to drugs predicted to be effective in vitro, while in 73 of 74 instances in which drug resistance had been predicted in vitro there was no response to treatment. 2 patients achieved a complete remission of 1 and 12+ months and 11 had partial remissions lasting a median of four months. Prediction of in-vitro resistance was 99% accurate. The 62% complete or partial remission rate to agents with proven in-vitro efficacy was achieved in extensively pretreated ovarian cancer patients who were unlikely to respond to empirically chosen secondary agents. The human tumour stem-cell assay, in which ovarian tumour colony-forming units are grown in a two-layer agar-culture system incorporating tests for drug sensitivity or resistance, can be effectively used to plan a suitable chemotherapy regimen for ovarian cancer patients.

Adenocarcinoma↗
PubMed1980

Antitumour activity and plasma kinetics of bleomycin by continuous and intermittent administration.

We have studied the cytotoxicity of bleomycin (4--10 u/kg/day for 6 days) given by continuous i.p. infusion (using an osmotic minipump) compared to daily i.p. bolus administration, against P388 leukaemic spleen colony-forming-units(LCFU-S). Continuous i.p. bleomycin at 8 u/kg/day caused a 0.5 log greater reduction of LCFU-S than did an identical dose given by intermittent bolus administration. The infusion minipump provided constant bleomycin plasma levels of 0.62 +/- 0.03 mu/ml and a total plasma AUC (area under the plasma decay curve) of 89.0 mu.h/ml for 6 days at 8 u/kg/day. Intermittent bolus bleomycin at 8 u.kg/day had a terminal-phase plasma t1/2 of 15 min and a total 6-day plasma AUC of 90.8mu.h/ml. These pharmacokinetic data validate the osmotic minipump as a constant drug-delivery system, and suggest that the two administration schedules resulted in equal total bleomycin dosages. Although high peak bleomycin plasma levels (i.e. 32 mu/ml) were achieved with the intermittent bolus administration, continuous-infusion bleomycin's greater inhibition of LCFU-S was probably related to the drug's schedule-dependent cell-killing characteristics. The results of this study provide further rationale for the continuing use of infusion bleomycin schedules in cancer patients.

Animals↗
PubMed1980

Influence of time and therapy on ventricular defibrillation in dogs.

Factors that may influence energy requirements for ventricular defibrillation include the duration of fibrillation and the mode of resuscitation. The present study assesses the effect of these influences on the energy needed for defibrillation. Dogs were anesthetized, and arterial blood pressure and Lead II of the ECG were continuously recorded. Ventricular fibrillation was electrically induced in each dog for a period of 1, 3, 5, or 9 min. Three resuscitation techniques were evaluated: precountershock artificial ventilation (AV) and closed-chest cardiac massage (CCCM); precountershock AV/CCCM and epinephrine, 1 mg IV; and countershock without preliminary AV/CCCM or epinephrine. Each animal was shocked with successive doses of 1, 2, 4, and 8 J/kg, ceasing when either electrical conversion occurred or after the maximum dose had been delivered. If defibrillation was unaccompanied by resumption of spontaneous circulation (systolic pressure greater than 60 mm Hg greater than 2 min), AV/CCCM was administered for 1 min. In general, the incidence of defibrillation was inversely proportional to the duration of fibrillation. Epinephrine had no significant effect on the energy dose needed for conversion. After 2 min of fibrillation, however, epinephrine became increasingly important for restoration of circulation. The technique of immediate countershock was effective for episodes of fibrillation limited to approximately 3 min. Regardless of therapy, for intervals of fibrillation of up to 6 min, Gompertz data curves indicated that a delivered energy of 4--5 J/kg is the approximate energy dose associated with the maximum achievable incidence of defibrillation within the limits of this experimental protocol.

Animals↗
PubMed1980

Comparison of bone scintigraphy and radiography in multiple myeloma.

Radionuclide images and skeletal radiographs of 51 patients with multiple myeloma were compared to assess the sensitivity of scintigraphy in detecting radiographically evident disease. Comparable studies were available for 562 sites. The radionuclide image was relatively insensitive in detecting myeloma; it failed to show radiographically evident disease or underestimated its extent at 27% of the sites. On a limited number of serial images there were 7 sites at which a scintigraphic abnormality preceded the radiographic abnormality. No definite correlation was found between scintigraphic findings and hematologic parameters of myeloma activity. Although the radionuclide image may demonstrate a few sites of myeloma before the radiograph, radiography remains the primary method of evaluating skeletal involvement by myeloma.

Adult↗
PubMed1980

Therapeutic synergism of hyperthermia-cis-platinum in a mouse tumor model.

A small-animal model was developed as a guide to whole-body hyperthermia in cancer patiens. Anesthetized DBA/2 mice were secured to a platform, and their hindlimbs were immersed in a 42.3 degrees C water bath for 30-60 minutes. Hindlimb hyperthermia reulted in steady-state rectal and femoral bone marrow and muscle temperatures of 42 degrees C and upper extremity muscle and esophagus temperatures of 41 degrees C. With this hyper thermia technique, the mouse spleen colony assay could be used to quantitate the lethality of hyperthermia and/or cis-dichloro-diammineplatinum(II) (cis-platinum) on clonogenic bone marrow and leukemia cells. Hyperthermia prior to cis-platinum administration increased cis-platinum inhibition of leukemia colony formation as much as 2 logs; however, antileukemia synergism ws greatest when cis-platinum administration immediately preceded hyperthermia and no evidence existd of synergism against normal bone marrow colonies. Correlative in vivo drug uptake studies showed a marked increase in leukemia cell uptake of 195mPt-cis-platinum at elevated temperatures, which suggested a potential mechanism for the apparent antileukemia synergism of cis-platinum and heat.

Animals↗
PubMed1980

Pretreatment tumor mass, cell kinetics, and prognosis in multiple myeloma.

One-hundred fifty patients with multiple (plasma cell) myeloma had pretreatment tumor mass staging, and 79 also had measurement of the pretreatment labeling index (LI%). There were clear differences in survival by pretreatment stage of disease. The pretreatment LI% of bone marrow plasma cells was an independent prognostic factor both in single factor and multivariate regression analyses, including myeloma stage (p less than 0.02). Other important prognostic factors (multivariate) included performance status, serum creatinine, presence of Bence Jones protein, age, and kappa/lambda subtype. A LI% of less than 1% was associated with long survival in each patient group. Patients with benign gammopathy had excellent survival and very low labeling indices. A pretreatment LI% of greater than 3% in high cell mass patients with a high total number of DNA synthesizing cells (S) conferred a very poor prognosis (p = 0.002). This subgroup of patients with high S values also had a high incidence of central nervous system relapse (27%), Bence Jones proteinuria, and elevated serum uric acid levels. We conclude that the pretreatment labeling index provides helpful prognostic information in addition to tumor mass staging.

Adult↗
PubMed1979

Superiority of nabilone over prochlorperazine as an antiemetic in patients receiving cancer chemotherapy.

Two double-blind, crossover trials comparing the antiemetic effectiveness of nabilone, a new synthetic cannabinoid, with that of prochlorperazine were conducted in patients with severe nausea and vomiting associated with anticancer chemotherapy. Of 113 patients evaluated, 90 (80 per cent) responded to nabilone therapy, whereas only 36 (32 per cent) responded to prochlorperazine (P less than 0.001). Complete relief of symptoms was infrequent, occurring only in nine patients (8 per cent) given nabilone. When both drugs were compared, both nausea (P less than 0.01) and vomiting episodes (P less than 0.001) were significantly lower in patients given nabilone. Moreover, patients clearly favored nabilone for continued use (P less than 0.001). Predominant side effects noted by patients were similar for both agents and included somnolence, dry mouth and dizziness but were about twice as frequent and more often severe in patients receiving nabilone. In addition, four patients (3 per cent) taking nabilone had side effects (hallucinations in three, hypotension in one) that required medical attention. Euphoria associated with nabilone was infrequent (16 per cent) and mild.

Adolescent↗
PubMed1979

Superiority of adriamycin-containing combination chemotherapy in the treatment of diffuse lymphoma: a Southwest Oncology Group study.

As a part of an ongoing prospective controlled trial, the Southwest Oncology Group compared the results of treatment of advanced non-Hodgkin's lymphoma with two CHOP regimens (cyclophosphamide, adriamycin, vincristine and prednisone with either low-dose bleomycin or BCG by scarification) to a COP regimen (cyclophosphamide, vincristine and prednisone) with low-dose bleomycin (COP-Bleo). The study design emphasized histopathology review and systematic restaging to define complete remission (CR). Confirmed rates of CR for 443 evaluable patients were 59% for 286 patients receiving the CHOP regimens and 59% for 157 patients receiving COP-Bleo. Rates of CR were higher for patients with nodular lymphoma (69%) compared to those with diffuse lymphoma (54%) (p = 0.005). For patients with nodular lymphoma there was no difference in CR rates according to treatment. For patients with diffuse lymphomas the CR rate was higher with the CHOP programs (58%) than with COP-Bleo (44%) (p = 0.10). Overall duration of CR and survival was significantly longer for patients with nodular lymphoma compared to diffuse lymphoma (p less than 0.01). At this time, remission duration and survival were similar regardless of induction regimen used in patients with nodular lymphoma. However, in patients with diffuse lymphoma, the duration of CR and overall survival were improved by treatment with the CHOP regimens compared to COP-Bleo (p = 0.02). Thus, in this controlled study we have demonstrated that initial combination chemotherapy employing the CHOP regimen was a superior remission induction therapy for patients with diffuse lymphoma.

Antineoplastic Agents↗
PubMed1979

Kinetics of intravenous melphalan.

We have studied the disposition and elimination of melphalan after intravenous administration in 9 patients with cancer. High-pressure liquid chromatography and 14C-melphalan were used to assay drug concentration in plasma and urine. Composite plasma t1/2alpha was 7.7 +/- 3.3 and t1/2beta was 108 +/- 20.8 min for 8 of the patients. The mean 24-hr urinary excretion of melphalan was 13.0 +/- 5.4% of the administered dose. In 2 patients, 80% to 100% of the measured 14C counts in plasma and urine samples at each study interval, up to 24 hr after drug administration, could be accounted for by the sum of parent compound, monohydroxy and dihydroxy products, and methanol nonextractable radioactivity (i.e., protein-bound activity). These data and evidence of rapid disappearance from plasma at 37 degrees in vitro suggest that spontaneous degradation, and not enzymatic metabolism, is the major determinant of the t1/2 of melphalan in vivo.

Adult↗
PubMed1979

Oral melphalan kinetics.

The systemic availability of melphalan after oral administration is not well known. Most patients are put on a fixed oral dosage regimen. We have studied the disposition of melphalan in 14 patients after single oral doses. Five were also studied after receiving the same dose intravenously. Oral melphalan had a mean plasma terminal phase half-life (t1/2) of 90 +/- 17 min. The mean area under the plasma concentration:time curve (CXT) was 53 +/- 33 micrograms . min/ml. Urinary excretion of oral melphalan averaged 10.9 +/- 4.9% during the first 24 hr. The CXT ratio (oral:intravenous) for the 5 patients studied after both oral and intravenous melphalal (0.6 mg/kg) ranged between 0.25 and 0.89 and averaged 0.56. After oral dosing in 14 fasting patients, the time at which melphalan first appeared in the plasma varied between 15 min and 6 hr. In a myeloma patient who took oral melphalan, no melphalan was found in plasma or urine up to 24 hr. Some instances of failure of tumor response to oral melphalan may be due to inadequate bioavailability rather than inherent tumor resistance.

Administration, Oral↗