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Biomedical subjects

S Wadler

Publications and source records attributed to S Wadler.

At least 91 records · Page 5Linked to original sources
PubMed1995

Audiological findings in a Phase I protocol investigating the effect of WR 2721, high-dose cisplatin and radiation therapy in patients with locally advanced cervical carcinoma.

WR 2721 (ethiofos) protects against the toxic effects of the heavy metal compound cisplatin, which is used in the treatment of solid tumours. In a Phase I protocol designed to determine the maximum dose of WR 2721 which could be tolerated when administered in combination with cisplatin and radiation therapy to patients with cervical carcinoma, 11 patients were evaluated by audiologic testing before and after cisplatin WR 2721 administration in an attempt to identify the degree of ototoxicity. Forty-five per cent were noted to have significant hearing threshold changes, predominantly in the high frequencies. There were no significant changes in the speech frequencies in this series. This contrasts with the greater degrees of ototoxicity observed in controls treated in the same way who received cisplatin without WR 2721 protection.

Amifostine↗
PubMed1995

Lack of efficacy of interferon-alpha therapy in recurrent, advanced cervical cancer.

Human papillomavirus (HPV) is associated with 65-95% of in situ or early invasive squamous cell carcinomas of the cervix. A multiinstitutional, prospective phase II clinical trial was initiated by the Eastern Cooperative Oncology Group (ECOG) to study the activity of IFN-alpha 2b in women with metastatic or locally recurrent cervix cancer. The activity of IFN-alpha 2b was correlated with the presence of HPV as measured by Southern blot hybridization or polymerase chain reaction techniques in 17 patients. All patients had failed prior definitive therapy with surgery, radiation, and chemotherapy. IFN-alpha 2b was administered at 10 MU/m2 subcutaneously three times per week. Among 31 patients enrolled, 3 achieved a clinical response to treatment. Tumor was accessible for biopsy in 17 patients. The presence of HPV was assayed by Southern blot hybridization (2 of 17) and/or polymerase chain reaction (PCR) technology (15 of 17). Of the 17 assays, 16 were informative. HPV was detected in 5 of 16 patients. Of 5 HPV-positive women, 2 responded to treatment, versus 1 of 11 HPV-negative women, thus not permitting reliable statistical analysis. It is concluded that IFN-alpha 2b has only minimal activity against advanced, recurrent cervical cancer.

Adult↗
PubMed1995

Phase I trial of the somatostatin analog octreotide acetate in the treatment of fluoropyrimidine-induced diarrhea.

PURPOSE: Diarrhea is one of the dose-limiting toxicities for administration of fluorouracil (5FU) in patients with gastrointestinal malignancies and can result in severe morbidities or mortality. The somatostatin analog octreotide acetate has been used in the treatment of 5FU-induced diarrhea with promising results. A phase I trial was initiated to determine the maximum-tolerated dose of octreotide acetate that could be administered in this setting. PATIENTS AND METHODS: Patients were required to have National Cancer Institute Common Toxicity Criteria > or = grade 2 diarrhea or watery diarrhea secondary to treatment with 5FU or a modulated 5FU regimen. At least three patients were treated at each dose level; after satisfactory completion of this dose level (zero of three or one of six patients with < or = grade 2 toxicity), additional patients were added at the next dose level. Doses of octreotide acetate studied were 50 to 2,500 micrograms subcutaneously three times daily for 5 days. RESULTS: A total of 35 patients received 49 courses of therapy. The only significant toxicities occurred at 2,500 micrograms. At this dose level, one patient developed an allergic reaction with flushing, nausea, and dizziness after each of the first two injections. A second patient developed asymptomatic hypoglycemia with a serum glucose level of 26 mg/dL. The maximum-tolerated dose was 2,000 micrograms. The efficacy of the treatment correlated significantly (P = .01) with the dose of octreotide administered, and more patients completed the course of therapy at the higher doses. CONCLUSION: Octreotide acetate can be safely administered for the treatment of fluoropyrimidine-induced diarrhea in patients with gastrointestinal malignancies. The dose-limiting toxicities were allergic (nausea, rash, and light-headedness) and endocrine (hypoglycemia). There was a significant correlation between complete response to therapy and octreotide dose.

Adult↗
PubMed1995

Modulation of 5-FU/alpha-interferon with high-dose continuous infusion hydroxyurea.

Biochemically modulated 5-fluorouracil (5-FU) regimens are active against several gastrointestinal malignancies. Hydroxyurea is an inhibitor of the enzyme ribonucleotide reductase. Despite successful in vitro studies, studies combining oral hydroxyurea with 5-FU based regimens have failed to demonstrate clinical synergy. Based on the pharmacokinetic properties of hydroxyurea, continuous exposure to the drug may be required to reproduce the synergy observed in vitro. We will review the pharmacology of hydroxyurea and the rationale for the modulation of 5-FU/alpha-interferon (IFN) with high-dose continuous infusion hydroxyurea.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1994

Utility of embolization or chemoembolization as second-line treatment in patients with advanced or recurrent colorectal carcinoma.

BACKGROUND: Second-line therapy of patients with colorectal cancer metastatic to the liver is unsatisfactory. One alternative to systemic treatment is therapy directed locoregionally. METHODS: Twenty-four patients with unresectable colorectal cancer with bulky liver metastases who had failed prior systemic therapy were randomized to treatment with either embolization or chemoembolization. For the embolization group, particulate transcatheter polyvinyl alcohol (PVA) (150-250-microns particles) mixed with full-strength iodinated radiographic contrast was administered under direct fluoroscopic control. In patients randomized to chemoembolization, 5-fluorouracil (750 mg/m2) and recombinant alpha-2a-interferon (Roche Laboratories, Nutley, NJ) (9-MU) were thoroughly mixed into the PVA contrast suspension. Study end points were response to therapy and survival. RESULTS: Of 24 patients, 13 were randomized to chemoembolization and 11 to embolization therapy. All were assessable for toxicity, response, and complications. Among the first 13 patients treated initially, a suppurative abscess developed in one patient, who died. Eleven subsequent patients were pretreated with oral and intravenous antibiotics without further infectious complications. Five patients had hemorrhagic complications, two of which were serious. The treatment was otherwise well tolerated, with most patients experiencing transient pain, fevers, and elevations in leukocyte counts and liver enzymes, which resolved spontaneously. Computed tomography scans of the liver were used to assess patient response to therapy. There were 6 responders (25%) among the 24 patients treated. No differences in response to treatment or survival between the embolization and chemoembolization groups were noted. With a median follow-up of more than 12 months, the median survival was 9.3 months from the time of embolization therapy. CONCLUSIONS: Embolization and chemoembolization therapy appear to have antitumor activity as second-line therapy in patients with colorectal carcinoma with bulky liver metastases. Although generally well tolerated, complications of this therapy may be severe. The addition of further patients to this trial will allow a rigorous comparison of embolization alone versus embolization with chemotherapy.

Adult↗
PubMed1994

New barriers to ventricular invasion in paraglottic laryngeal cancer.

BACKGROUND: Anatomic barriers to the spread of laryngeal cancer include the conus elasticus, the quadrangular membrane, and the thyroid cartilage. It has been speculated that an elastic barrier surrounds and protects the ventricle. METHODS: The authors studied the microanatomic patterns of spread of 17 cases of patients who had laryngeal cancer with paraglottic disease and confirmed their findings by examining normal autopsy specimens. RESULTS: Five patients of the seventeen cases showed no ventricular mucosal involvement despite extensive paraglottic disease. Both an inner, central, subepithelial periventricular elastic membrane barrier were identified; the latter was in continuity with the conus elasticus and quadrangular membrane. CONCLUSIONS: Two weak fibroelastic barriers surround the ventricle. The outer, peripheral, fibroelastic membrane is contiguous with the conus elasticus and the quadrangular membrane. Therefore, ventricular involvement is not a sensitive indicator of paraglottic spread. Squamous cell cancer may grow around the periventricular barriers to involve both the true and false cords but may spare the ventricle. The prognostic significance of the violation or preservation of the periventricular elastic barriers is unknown.

Carcinoma, Squamous Cell↗
PubMed1994

Potentiation of the antitumor activity of 5-fluorouracil in colon carcinoma cells by the combination of interferon and deoxyribonucleosides results from complementary effects on thymidine phosphorylase.

alpha-Interferon (IFN alpha) potentiates the cytotoxicity of 5-fluorouracil (FUra) in vitro, and the combination has clinical efficacy in advanced colorectal cancer. We have reported previously an IFN alpha-mediated elevation in cellular FdUMP levels accompanied by the stimulation of thymidine phosphorylase (TP) activity in extracts from HT-29 human colon carcinoma cells treated with IFN alpha. We have now found that this effect of IFN alpha can be measured in vivo as an increase in thymine incorporation in intact cells. The increase was only 3-fold, however, compared to the 12-fold increase seen in TP activity in cell extracts. This suggested that the cosubstrate for TP, deoxyribose-1-phosphate, was rate limiting in the cells. Since the synthetic pathway of TP can also proceed via a transferase reaction, natural and modified deoxyribonucleosides were tested as deoxyribosyl donors. TP activity was measurable in cell extracts using deoxyinosine as cosubstrate with either thymine or FUra, although activity was only 10% of that measured with deoxyribose-1-phosphate. The pyrimidine analogue 5-propynyloxy-2'-deoxyuridine (PO-dUrd) had 15% of the maximal TP activity in cell extracts and also increased thymine incorporation in intact cells 10-fold. Both 2'-deoxyinosine and PO-dUrd potentiated the cytotoxicity of FUra by 8-11-fold. IFN alpha potentiated the cytotoxicity of FUra by 1.8-fold, and the combination of IFN alpha and PO-dUrd produced a 25-fold increase in the cytotoxicity of FUra. Neither the corresponding analogue riboside, 5-propynyloxyuridine, nor the analogue base, 5-propynyloxyuracil, had any effect on FUra cytotoxicity. There was a significant correlation between the ability of a nucleoside and/or IFN alpha combination to increase thymine incorporation and to reduce the 50% inhibitory concentration for FUra. IFN alpha and PO-dUrd also potentiated the inhibition by FUra of thymidylate synthase activity. These findings suggest that the use of a deoxyribonucleoside to provide the rate limiting cosubstrate would complement the stimulation of TP by IFN alpha, and together they should further enhance the antitumor activity of FUra.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1994

Phase II trial of echinomycin in patients with advanced or recurrent colorectal cancer.

Echinomycin is a novel bifunctional intercalating agent derived from Streptomyces echinatus. A phase II clinical trial of echinomycin in patients with advanced, measurable colorectal cancer was initiated to determine the efficacy and toxicities of this agent. Echinomycin, 1.5 mg/m2, was given initially as a 30- to 60-min infusion every 4 weeks. After 4 episodes of anaphylaxis had occurred among the first 14 patients, the schedule was changed to a 24-h infusion, and an additional 16 patients were treated on this schedule. Treatment was given every 3 weeks. A total of 30 patients were eligible and evaluable; there were 3 (10%; 90% confidence interval, 3%-23%) clinical responses lasting 3, 3+, and 12 months, respectively. The most serious toxicity encountered was anaphylaxis, which occurred in 5 patients, although with no serious sequelae. A premedication regimen with dexamethasone, diphenhydramine, and cimetidine and a change of the duration of the infusion to 24 h reduced the incidence of this complication. Grade 2-3 vomiting occurred among earlier patients treated; however, with the 24-h schedule this toxicity was substantially reduced. The sole important case of hematologic toxicity was a single patient with grade 3 thrombocytopenia. Echinomycin employed in this dose and schedule had modest activity against colorectal cancer, comparable with that observed with 5-fluorouracil. Further studies in patients with gastrointestinal malignancies using a 24-h infusion with a dexamethasone premedication regimen similar to that employed prior to administration of taxol may be warranted.

Adenocarcinoma↗
PubMed1994

Biologic agents as biochemical modulators: pharmacologic basis for the interaction of cytotoxic chemotherapeutic drugs and interferon.

Biochemical modulation of cytotoxic cancer chemotherapeutic agents is one means of enhancing the activity and selectivity of antitumor drugs. Traditionally this approach has utilized detailed information regarding a particular enzymatic reaction or biochemical pathway to develop potential modulating agents. In contrast, the reported clinical therapeutic activity of IFN in combination with cytotoxic agents has prompted a reexamination of the biochemical actions of the cytokine. Interferon elicits a number of cellular actions that might contribute to its pharmacologic activity, including both direct antitumor effects and host-mediated actions. The best understood are those related to the cytotoxicity of the fluoropyrimidine antimetabolites and include enzymatic reactions involved in fluoropyrimidine metabolic activation, catabolism, and interaction with its target enzyme. However, even in this instance, a mechanistic association of a specific pharmacologic action with therapeutic activity remains to be determined. These studies demonstrate that cytokines and other biologic agents may exert specific biochemical modulations that augment (or potentially attenuate) the activity of the cytotoxic chemotherapeutic agents.

Animals↗
PubMed1993

Phase I trial of cyclophosphamide, doxorubicin, and 5-fluorouracil plus interferon-alpha 2b in patients with advanced breast cancer.

alpha-Interferon (IFN-alpha) enhances the activity of 5-fluorouracil in patients with advanced colorectal carcinoma. Preclinical evidence suggests a similar potential role for IFN-alpha combined with cyclophosphamide, doxorubicin (Adriamycin, Adria Laboratories, Columbus, OH), and 5-fluorouracil (CAF) in advanced adenocarcinoma of the breast. To determine a maximum tolerated dose of IFN-alpha that could be combined with CAF and that did not compromise CAF dose intensity and to determine the effect of IFN-alpha on the pharmacokinetics of doxorubicin, a phase I study of IFN-alpha plus CAF was performed by the Eastern Cooperative Oncology Group. Nine patients with advanced breast cancer received CAF (cyclophosphamide at 100 mg/m2/day p.o. on days 1-14, doxorubicin at 30 mg/m2 and 5-fluorouracil at 500 mg/m2 i.v. bolus on days 1 and 8) plus IFN-alpha (1 milliunit/m2, n = 6, or 2 milliunits/m2, n = 3) given s.c. on days 1, 3, 5, and 8 (1 h prior to the doxorubicin and 5-FU injection on days 1 and 8) of each cycle every 28 or more days. Escalation of the IFN-alpha dose occurred in cohorts of 3-6 patients if a dose-limiting toxic event (neutropenic fever, platelet nadir of < 25,000/microliters, > 2-week treatment delay, or a > 50% dose reduction in day 8 CAF) occurred during the first two cycles in 0 of 3 or 1 of 6 patients. During cycle 1, IFN-alpha was omitted on day 1, and multiple plasma samples were drawn on day 1 (without IFN-alpha) and day 8 (with IFN-alpha) after each doxorubicin injection and were analyzed for plasma doxorubicin concentration. The maximum tolerated dose of IFN-alpha by our criteria was 1 milliunit/m2, and neutropenia was the predominant toxic effect that precluded IFN-alpha dose escalation. The dose intensity of CAF achieved with IFN-alpha was identical to that for CAF alone observed in prior studies. IFN-alpha had no significant effect on the pharmacokinetics of doxorubicin, although 3 of 7 patients studied had reduced doxorubicin clearance, ranging from 32% to 69%. Alternative CAF drug delivery schedules (all drugs given i.v. every 3-4 weeks) that are more amendable to hematopoietic growth factor support may be more suitable to combine with higher doses of IFN-alpha that may produce modulation.

Adenocarcinoma↗
PubMed1993

Treatment of carcinoma of the esophagus with 5-fluorouracil and recombinant alfa-2a-interferon.

BACKGROUND: Combinations of 5-fluorouracil (5FU) and recombinant alfa-2a-interferon (IFN) are synergistic in vitro and have demonstrated activity in colorectal carcinoma, renal cell carcinoma, and urothelial tumors. METHODS: A Phase II trial of the combination of 5FU, 750 mg/m2 daily x 5 followed by weekly bolus therapy, and IFN, 9 MU subcutaneously three times per week, was initiated in patients with esophageal carcinomas. Patients were required to have biopsy-proven squamous cell or adenocarcinoma of the esophagus, locally advanced or metastatic disease beyond the scope of surgical resection, and adequate performance status, renal, hepatic, and bone marrow function. RESULTS: Twenty-one patients were enrolled; one patient was inevaluable for response because he had received prior chemotherapy, but was evaluated for toxicity. Eleven patients had metastatic disease, and 10 had locally advanced disease. Thirteen patients had squamous cell carcinoma and 8 adenocarcinoma. Toxicities were acceptable with no serious diarrhea and only two cases of serious stomatitis, although a greater than expected incidence of neurologic toxicity was observed. There were five responders (25%) including two patients with advanced or locally advanced disease rendered pathologically free of disease. One patient, initially considered surgically unresectable, was able to undergo a total thoracic esophagectomy after responding to treatment with 5FU/IFN, at which time only a single microscopic focus of carcinoma in situ was found. She remains alive and free of disease at 18+ months. A second patient who presented with metastatic disease and nearly complete obstruction of the esophagus regained normal swallowing function after treatment with 5FU/IFN; rebiopsy of all lesions revealed the patient to be pathologically free of disease. He survived over 2 years. CONCLUSIONS: This regimen employing a single cytotoxic agent has activity in esophageal carcinoma. Strategies employing biochemical modulation deserve additional investigation in the treatment of esophageal carcinoma.

Adenocarcinoma↗
PubMed1993

Pilot trial of cisplatin, radiation, and WR2721 in carcinoma of the uterine cervix: a New York Gynecologic Oncology Group study.

PURPOSE: A phase I trial of WR2721 was initiated to determine the maximal safe dose for incorporation into a consecutive 5-day schedule of cisplatin administered concurrently with radiation therapy in patients with cervical cancer. PATIENTS AND METHODS: WR2721 was administered at 340 to 910 mg/m2/d immediately before cisplatin. Cisplatin was administered at 20 mg/m2/d for 5 days every 3 weeks in combination with external-beam radiation therapy and at 100 mg/m2 after each brachytherapy treatment. Pelvic radiation consisted of external-beam therapy to a dose of 39.6 Gy, followed by brachytherapy with cesium 137 tandem and ovoid insertions to deliver 80 Gy to point A and 55 Gy to point B. RESULTS: Twenty patients were enrolled; 19 were assessable. The dose-limiting toxicity of WR2721 was hypotension. No patients developed serious sequelae, but hypotension required a reduction in the dose of WR2721 at the highest dose level tested. The major grade 3 or 4 toxicities included transient azotemia (five of 19), leukopenia (nine of 19), vomiting (four of 19), and neurotoxicity (two of 19). One patient experienced an anaphylactic reaction to cisplatin. CONCLUSION: The recommended dose of WR2721 administered in conjunction with cisplatin on a daily x 5 schedule plus radiation therapy is 825 mg/m2/d for 5 days.

Adenocarcinoma↗
PubMed1993

Management of hypocalcemic effects of WR2721 administered on a daily times five schedule with cisplatin and radiation therapy. The New York Gynecologic Oncology Group.

PURPOSE: To determine the effects of the chemoprotective agent, WR2721, administered on a daily x 5 schedule with cisplatin and radiation therapy, on calcium and parathyroid hormone (PTH) levels. PATIENTS AND METHODS: Twenty women with cervical cancer were enrolled in a clinical trial to determine the maximal safe dose of WR2721 plus radiation therapy and cisplatin on a novel daily x 5 schedule. Detailed studies of the effects of WR2721 on calcium and PTH levels were initiated after a patient developed symptomatic hypocalcemia. RESULTS: Treatment with WR2721 resulted in a rapid decline in serum PTH levels within 4 hours, which fell below the lower limits of normal at 24 hours, then returned to within normal limits at 48 hours. In contrast, serum levels of ionized calcium were not affected acutely, and declined by only 7% within 24 hours. However, this small decrease persisted for the 5 days of treatment. Hypocalcemic effects were successfully managed with oral calcium carbonate and calcitriol supplements. In one patient, particularly sensitive to the effects of WR2721, serum levels of ionized calcium decreased to less than 3.0 mg/dL despite oral calcium supplements. CONCLUSION: The effects of WR2721 on serum ionized calcium levels are mediated by direct inhibition of PTH activity; other effects such as inhibition of renal tubular calcium reabsorption cannot be excluded. We recommend that patients treated with WR2721, cisplatin, and radiation therapy receive routine oral calcium and calcitriol supplementation and that serum ionized calcium levels be monitored frequently.

Adult↗
PubMed1993

Phase I trial of low-dose, prolonged continuous infusion fluorouracil plus interferon-alfa: evidence for enhanced fluorouracil toxicity without pharmacokinetic perturbation.

PURPOSE: To determine the maximum-tolerable dose (MTD) of fluorouracil (5-FU) administered as a low-dose, prolonged continuous intravenous infusion (PCI) plus interferon-alfa (IFN-alpha) that would permit treatment for at least 28 consecutive days, and to determine the effect of IFN-alpha on 5-FU pharmacokinetics. PATIENTS AND METHODS: Twenty-six assessable patients with advanced cancer received low-dose PCI 5-FU (150, 200, 250, and 300 mg/m2/d) plus IFN-alpha, 5 x 10(6) IU/m2 administered subcutaneously (SC) at hour 48 of the 5-FU infusion, then thrice weekly thereafter in cohorts of at least three patients. Treatment continued until treatment-limiting toxicity (TLT) developed, such as mucositis, diarrhea, or fatigue. Escalation to the next 5-FU dose level occurred if none of three or zero to two of six patients developed TLT before day 28. Quantitation of plasma 5-FU concentration by high-performance liquid chromatography was performed in 15 patients. Data were standardized using the Cosinor method and compared before and after IFN-alpha administration using the paired t test. RESULTS: The mean number of days of continuous 5-FU therapy for patients receiving 150, 200, 250, and 300 mg/m2/d of 5-FU plus IFN alfa-2a (IFN-alpha 2a) was 75, 54, 37, and 22 days, respectively. The MTD of PCI 5-FU by our criteria that could be combined with IFN-alpha was 250 mg/m2/d. Comparison of the standardized pharmacokinetic data showed no significant effect of IFN-alpha on plasma 5-FU concentration, and no alteration of the normal circadian variation in plasma 5-FU concentration that was evident before IFN-alpha administration. Objective response occurred in patients with adenocarcinoma of the pancreas (n = 3), kidney (n = 2), and lung (n = 1). CONCLUSION: IFN-alpha substantially enhanced the gastrointestinal toxicity of low-dose PCI 5-FU without affecting 5-FU pharmacokinetics, contrary to previous reports using alternative 5-FU schedules in which IFN-alpha-related enhancement of 5-FU toxicity was attributable to reduced 5-FU clearance. Our findings suggest that under certain conditions, mechanisms other than altered 5-FU pharmacokinetics may be responsible for the ability of IFN-alpha to enhance the toxic effects of 5-FU.

Adult↗
PubMed1993

Mechanisms by which interferon potentiates chemotherapy.

IFNs potentiate the activity of multiple chemotherapy drugs in vitro; improved activity has been noted with 5-FU and IFN-alpha against colon carcinoma and with IFN-alpha and DTIC against melanoma. The mechanisms whereby interferon potentiates the activity of chemotherapeutic drugs are complex, and different mechanisms may be operative with different drugs and against different tumors. Both indirect immunoaugmentative effects of interferon and direct biochemical modulation of the drugs (as documented in detail with 5-FU) may play a role; further elucidation of these mechanisms will enable us to optimally utilize the combination of interferon and antineoplastic agents.

Animals↗
PubMed1993

N-(phosphonacetyl)-L-aspartate synergistically enhances the cytotoxicity of 5-fluorouracil/interferon-alpha-2a against human colon cancer cell lines.

Recombinant interferon-alpha (IFN) enhances the cytotoxic effects of the fluorinated pyrimidine, 5-fluorouracil (5FU), against two human colon cancer cell lines. The aspartate transcarbamylase (ATCase) inhibitor, N-(phosphonacetyl)-L-aspartate (PALA), was studied in combination with 5FU/IFN to determine whether further anti-pyrimidine effects would result in greater cytotoxicity. By median effects analysis PALA synergistically augmented the cytotoxic effects of 5FU/IFN against both human colon cancer cell lines. This occurred in the absence of any effects of 5FU/IFN on ATCase and without further potentiation of the PALA-mediated inhibition of ATCase. To explore the mechanism by which this interaction occurred, detailed studies of pools of dNTPs were performed. Both 5FU/IFN and PALA/5FU/IFN treatments resulted in early (2-8 hr) depletion of pools of dTTP, but no effects on pools of dCTP. PALA had no effect on dTTP pools either alone or in the combination. In contrast, both PALA and PALA/5FU/IFN treatments resulted in later (12-24 hr) depletion of pools of dCTP. 5FU/IFN treatment had no effect on these pools. When pools of dCTP and dTTP were repleted by treatment with cytidine or thymidine, 20 microM, however, there was only partial reversal of cytotoxicity induced by 5FU/IFN + PALA, suggesting that the synergy observed did not result solely from a sequential anti-pyrimidine effect. The incorporation of 5FU into RNA was also studied; PALA enhanced the incorporation of [6-3H]5FU into RNA by 83-150%, but not into DNA, suggesting an alternative mechanism of drug interaction.

Antineoplastic Combined Chemotherapy Protocols↗