Biomedical subjects

J Arseneau

Publications and source records attributed to J Arseneau.

At least 19 recordsLinked to original sources

PubMed2001

Phase II trial of intratumoral administration of ONYX-015, a replication-selective adenovirus, in patients with refractory head and neck cancer.

PURPOSE: To determine the safety, humoral immune response replication, and activity of multiple intratumoral injections of ONYX-015 (replication selective adenovirus) in patients with recurrent squamous cell carcinoma of the head and neck (SCCHN). PATIENTS AND METHODS: This phase II trial enrolled patients with SCCHN who had recurrence/relapse after prior conventional treatment. Patients received ONYX-015 at a dose of 2 x 10(11) particles via intratumoral injection for either 5 consecutive days (standard) or twice daily for 2 consecutive weeks (hyperfractionated) during a 21-day cycle. Patients were monitored for tumor response, toxicity, and antibody formation. RESULTS: Forty patients (30 standard and 10 hyperfractionated) received 533 injections of ONYX-015. Standard treatment resulted in 14% partial to complete regression, 41% stable disease, and 45% progressive disease rates. Hyperfractionated treatment resulted in 10% complete response, 62% stable disease, and 29% progressive disease rates. Treatment-related toxicity included mild to moderate fever (67% overall) and injection site pain (47% on the standard regimen, 80% on the hyperfractionated regimen). Detectable circulating ONYX-015 genome suggestive of intratumoral replication was identified in 41% of tested patients on days 5 and 6 of cycle 1; 9% of patients had evidence of viral replication 10 days after injection during cycle 1, and no patients had evidence of replication > or = 22 days after injection. CONCLUSION: ONYX-015 can be safely administered via intratumoral injection to patients with recurrent/refractory SCCHN. ONYX-015 viremia is transient. Evidence of modest antitumoral activity is suggested.

Adenovirus E1B Proteins↗

PubMed2001

A dose-finding and safety study of novel erythropoiesis stimulating protein (NESP) for the treatment of anaemia in patients receiving multicycle chemotherapy.

Darbepoetin alfa is a novel erythropoiesis stimulating protein (NESP), which stimulates erythropoiesis by the same mechanism as recombinant human erythropoietin (rHuEPO). NESP has been shown to be safe and efficacious in patients with chronic renal failure. NESP is biochemically distinct from rHuEPO, due to its increased sialic acid content. NESP has an approximately 3-fold greater half-life. rHuEPO has been shown to be safe and effective for the treatment of chemotherapy-induced anaemia. This study assessed the safety and efficacy of NESP administered once per week, under the supervision of a physician, to patients with solid tumours who were receiving multicycle chemotherapy for up to 12 weeks. Three dose cohorts are presented in this sequential, unblinded and dose-escalating study. Thirteen to 59 patients received NESP (0.5, 1.5 or 2.25 mcg kg(-1)wk(-1)) in each cohort. Patients were monitored for adverse events, including antibody formation to NESP and for effects on haemoglobin. NESP appeared to be well tolerated. Adverse events were similar across all cohorts and were consistent with the population being studied. No antibody formation was detected over the 16-week study period and follow-up. A dose-response relationship was evident for NESP and multiple measures of efficacy, including proportion of patients responding to NESP and the mean change in haemoglobin by week 4 and end of treatment for NESP 0.5, 1.5 and 2.25 mcg kg(-1)wk(-1)cohorts (mean change in haemoglobin at end of treatment was 1.24, 1.73 and 2.15 g dl(-1)respectively). Controlled studies of this agent at higher doses and less frequent schedules of administration are ongoing.

Adult↗

PubMed2000

Selective replication and oncolysis in p53 mutant tumors with ONYX-015, an E1B-55kD gene-deleted adenovirus, in patients with advanced head and neck cancer: a phase II trial.

ONYX-015 is an E1B-55kDa gene-deleted adenovirus engineered to selectively replicate in and lyse p53-deficient cancer cells. To evaluate the selectivity of ONYX-015 replication and cytopathic effects for the first time in humans, we carried out a Phase II clinical testing of intratumoral and peritumoral ONYX-015 injection in 37 patients with recurrent head and neck carcinoma. Patients received ONYX-015 at a daily dose of 1 x 10(10) plaque-forming units (pfu) via intratumoral injection for 5 days during week 1 of each 3-week cycle (n = 30; cohort A), or 1 x 10(10) pfu twice a day for 10 days during weeks 1 and 2 of each 3-week cycle. Posttreatment biopsies documented selective ONYX-015 presence and/or replication in the tumor tissue of 7 of 11 patients biopsied on days 5-14, but not in immediately adjacent normal tissue (0 of 11 patients; P = 0.01). Tissue destruction was also highly selective; significant tumor regression (>50%) occurred in 21% of evaluable patients, whereas no toxicity to injected normal peritumoral tissues was demonstrated. p53 mutant tumors were significantly more likely to undergo ONYX-015-induced necrosis (7 of 12) than were p53 wild-type tumors (0 of 7; P = 0.017). High neutralizing antibody titers did not prevent infection and/or replication within tumors. ONYX-015 is the first genetically engineered replication-competent virus to demonstrate selective intratumoral replication and necrosis in patients. This agent demonstrates the promise of replication-selective viruses as a novel therapeutic platform against cancer.

Adenovirus E1B Proteins↗

PubMed2000

Comparison of endocervical curettage and endocervical brushing.

OBJECTIVE: To compare endocervical brushing with endocervical curettage with respect to diagnostic yield by histology and patient discomfort. METHODS: Nonpregnant women referred for colposcopy because of abnormal Papanicolaou test results were randomized to endocervical sampling with either a metal curette (endocervical curettage [ECC]) or an endocervical brush. Extensive endocervical canal brushing was performed. All samples were submitted for histologic study. Results were evaluated against the histologic findings in electroconization specimens in a masked fashion. Pain scores were recorded using Melzack's Present Pain Intensity Scale. RESULTS: During the study period, 315 patients were randomized to the techniques: 157 to ECC and 158 to endocervical brushing. Of the 315 patients, 147 also underwent electroconization. Overall false-positive rates were 28.6% for endocervical brushing and 30.8% for ECC. False positives were due to contamination of the endocervical sample by lesional epithelium near the external os. The proportion of scanty specimens obtained by endocervical brushing (7. 6%) was higher than that obtained by ECC (2.5%) (P =.041). One sample obtained by brushing was insufficient for diagnosis; none obtained by ECC were insufficient. There were no statistically significant differences in the median pain scores between the two groups. CONCLUSION: The techniques were similar in terms of diagnostic yield and patient discomfort. Endocervical brushing had lower false-positive rates than those reported in the literature for cytologic analysis. Although ECC remains the method of choice for evaluation of the endocervical canal, brushing is an acceptable alternative.

Adult↗

PubMed2000

a controlled trial of intratumoral ONYX-015, a selectively-replicating adenovirus, in combination with cisplatin and 5-fluorouracil in patients with recurrent head and neck cancer.

ONYX-015 is an adenovirus with the E1B 55-kDa gene deleted, engineered to selectively replicate in and lyse p53-deficient cancer cells while sparing normal cells. Although ONYX-015 and chemotherapy have demonstrated anti-tumoral activity in patients with recurrent head and neck cancer, disease recurs rapidly with either therapy alone. We undertook a phase II trial of a combination of intratumoral ONYX-015 injection with cisplatin and 5-fluorouracil in patients with recurrent squamous cell cancer of the head and neck. There were substantial objective responses, including a high proportion of complete responses. By 6 months, none of the responding tumors had progressed, whereas all non-injected tumors treated with chemotherapy alone had progressed. The toxic effects that occurred were acceptable. Tumor biopsies obtained after treatment showed tumor-selective viral replication and necrosis induction.

Adenoviruses, Human↗

PubMed1999

Alpha-difluoromethylornithine as treatment for metastatic breast cancer patients.

DFMO (alpha-difluoromethylornithine) is an oral irreversible inhibitor of ornithine decarboxylase, the first rate-limiting enzyme in polyamine synthesis. DFMO has been shown to have antiproliferative effects against several human cancers, and some studies have suggested that DFMO may have pro-apoptotic and anti-invasive properties as well. DFMO is well tolerated with minimal toxicity but has been associated with ototoxicity with prolonged daily administration. We conducted a Phase I/II tolerability, pharmacokinetic, and efficacy study of high-dose DFMO in metastatic breast cancer patients. Twenty-one patients were treated with 4800 mg of DFMO p.o. three times a day for 14 days, followed by a 2-week drug holiday on a 28-day cycle. Urinary polyamine and blood DFMO levels were measured at multiple time points during therapy. High-dose DFMO was well tolerated, and no clinically significant ototoxicity was noted. No patient achieved an objective antitumor response; however, one patient with heavily pretreated liver metastases has achieved stable disease for 18 months to date on DFMO. Putrescine, spermine, and spermidine urinary levels were suppressed with DFMO treatment and remained low during the 2-week drug holiday. High-dose DFMO on a schedule of 2 weeks on treatment followed by 2 weeks off is well tolerated, is not associated with ototoxicity, and leads to sustained suppression of urinary polyamine levels. Although not an active cytotoxic agent for metastatic breast cancer, the intriguing prolonged growth arrest of liver metastases in one patient highlights the potential clinical growth inhibitory properties of DFMO. We believe that DFMO is worthy of study as adjuvant therapy in primary breast cancer patients and as a chemopreventive agent.

Adult↗

PubMed1996

Phase II evaluation of altretamine for advanced or recurrent squamous cell carcinoma of the cervix: a Gynecologic Oncology Group Study.

A Phase II trial was conducted by the Gynecologic Oncology Group to determine the activity of altretamine in previously treated patients with squamous cell carcinoma of the cervix. Thirty-two women with advanced or recurrent squamous cell carcinoma of the cervix were entered. The starting dose was 260 mg/m2/day for 21 days every 4 weeks. Twenty-six patients were evaluable for response and 29 were evaluable for toxicity. Among the 26 evaluable patients, 21 had received prior radiotherapy and 24 had received prior chemotherapy. A median of two courses were given (range, 1-6). Grade 3 or 4 gastrointestinal toxicity, occurring in 17%, was the most common complication (grade 3, 13.8%; grade 4, 3.4%). Grade 3 anemia was slightly less common occurring in 13.8%. Grade 3 peripheral neurotoxicity occurred in 3.4%. There were no objective responses, demonstrating that this agent is useful in previously treated squamous cell carcinoma of the cervix.

Altretamine↗

PubMed1996

Loop electrosurgical excision procedure for squamous intraepithelial lesions of the cervix: advantages and potential pitfalls.

OBJECTIVE: to evaluate the advantages and pitfalls of the loop electrosurgical excision procedure as applied to the diagnosis and treatment of cervical cancer precursors. METHODS: Loop electrosurgical excision procedure using local anesthesia and colposcopic guidance was performed in an outpatient clinical setting in 1189 consecutive patients referred for colposcopy for an abnormal Papanicolaou smear during a period of 4 years. RESULTS: Of the 1189 patients, 915 (77%) were managed in one sitting with the "see and treat" approach, and in 274 patients endocervical curettage and cervical biopsies preceded loop electrosurgical excision procedure. One hundred nineteen (10%) patients were lost to follow-up. Twenty-one patients had either adenocarcinoma in situ (15) or microinvasive squamous cell carcinoma (six) in the loop electrosurgical excision procedure specimen, whereas the electroexcised specimens contained no lesional tissue in 166 (14%) patients. Cure (ie, disease-free at 6 months or longer) was observed in 92% of the 883 evaluable patients after a single treatment and 95% after a repeat loop electrosurgical excision procedure. High-grade squamous intraepithelial lesion was successfully treated with loop electrosurgical excision procedure in 287 (93%) of 309 patients. Complications, mainly intra- and postoperative bleeding, occurred in 7% of the patients. In most loop electrosurgical excision procedure-negative cases, the referral cytologic diagnosis or colposcopy and/or history were false-positive on review, or the biopsies performed before loop electrosurgical excision procedure removed smaller areas of abnormal tissue. CONCLUSION: Loop electrosurgical excision procedure using the see and treat approach should be limited to cytologically and colposcopically unequivocal intraepithelial lesions, and depth of excision should be controlled by colposcopy using loop electrodes of appropriate size. In doubtful cases, particularly in the young patient, disease should be ascertained by expert histology and colposcopy before definite therapy. Loop electroexcision represents an attractive means of diagnosing and treating cervical cancer precursors.

Adenocarcinoma↗

PubMed1996

Diagnostic performance of Hybrid Capture human papillomavirus deoxyribonucleic acid assay combined with liquid-based cytologic study.

OBJECTIVE: Our purpose was to determine the diagnostic performance of human papillomavirus deoxyribonucleic acid testing when performed on liquid-based (Thin-prep) cytologic samples. STUDY DESIGN: Thin-prep cytologic study, human papillomavirus deoxyribonucleic acid assay with probes for high oncogenic risk human papillomavirus types (16, 18, 31, 33, 35, 45, 51, 52, and 56), and cervical biopsies on women referred to colposcopy for an abnormal Papanicolaou smear were performed. RESULTS: Of the 364 patients, 186 (51.6%) had a low-grade squamous intraepithelial lesion or worse by histologic diagnosis. Human papillomavirus deoxyribonucleic acid quantitation was correlated with a histologic diagnosis of squamous intraepithelial lesion (p < 0.0001) and the morphologic severity (p < 0.01). The combination of Thin-prep cytologic study and human papillomavirus deoxyribonucleic acid testing correctly identified 87.7% of histologic low-grade lesions and 95.1% of the women with high grade lesions and invasive cancer (p < 0.01). CONCLUSIONS: A liquid-based cytologic system provides adequate material for concomitant human papillomavirus testing. Addition of human papillomavirus testing to Thin-prep cytologic study provides significant gains in diagnostic accuracy over either cytologic study or human papillomavirus deoxyribonucleic acid testing alone.

Adolescent↗

PubMed1996

Human papillomavirus DNA in invasive cervical carcinomas and its association with patient survival: a nested case-control study.

This study sought to examine the association between the presence of human papillomavirus (HPV) DNA in invasive cervical cancer and prognosis. A case-control study was undertaken nested in a cohort of 208 patients with invasive cervical carcinoma in Montreal. All 40 deceased patients formed the case groups. A control group of equal size was selected by matching to each case (1:1) a patient of the same age and year of admission who had survived her disease. HPV DNA was detected by the use of a PCR protocol. The odds ratio (OR) for cervical cancer death was computed by logistic regression. Detection of HPV, particularly of types 16 and 18, was negatively correlated with disease stage and histological grade. The OR for death was 0.27 [95% confidence interval (CI), 0.1-0.8] for those whose tumors were positive for HPV DNA versus those in whom HPV DNA was not detected. After adjusting for the confounding effects of stage and grade, the prognostic effect was somewhat reduced, with an OR of 0.34 (CI, 0.1-1.1), which was no longer significant. The magnitude of the HPV-survival association was not altered when the analyses were restricted to carcinomas of stages I and II. Regardless of the mechanism for the prognostic role, detection of HPV DNA in primary tumors may play an important adjunct role in assessing prognosis of patients with invasive cervical cancer.

Adult↗

PubMed1995

Clear cell adenosquamous carcinoma of the cervix. An aggressive tumor associated with human papillomavirus-18.

BACKGROUND: It is well recognized that adenocarcinomas and adenosquamous carcinomas of the cervix are frequently associated with human papillomavirus (HPV)-16 or -18. However, few studies have investigated associations between histologic variants of these tumors and specific types of HPV. METHODS: Eleven cases of cervical adenosquamous carcinoma with an unusual histologic appearance were characterized using histochemical and immunohistochemical stains. Sections were tested for the presence of HPV DNA using the polymerase chain reaction (PCR) and type specific primers for HPV-16 and -18. Clinical outcome was determined from a chart review. RESULTS: All tumors were histologically characterized by the presence of sheets of cohesive cells with prominent cell borders and a vacuolated or clear cytoplasm containing large amounts of glycogen. All tumors had focal gland formation and stained positive with mucicarmine stain. Using PCR, HPV-18 DNA was identified in all cases. The youngest patient was 24 years old and the oldest 74 years (mean, 43 years). Eight (73%) of the 11 patients have developed recurrent disease with a mean follow-up until recurrence of 9.5 months (range, 3-22 months). Seven (64%) of the 11 patients have died of their cervical tumors. Of the five patients with Stage IB disease, three (60%) have died of their cervical tumors. CONCLUSIONS: A subset of invasive cervical adenosquamous carcinoma associated with HPV-18 that has a distinctive histologic appearance and an aggressive clinical course is described. The term "clear cell adenosquamous carcinoma" is proposed for this unique variant of invasive cervical carcinoma.

Adenocarcinoma, Clear Cell↗

PubMed1994

Histopathological and adhesion formation after incision using ultrasonic vibrating scalpel and regular scalpel in the rat.

OBJECTIVE: To evaluate and to compare changes that occur in the uterine tissue of the rat after a standard incision with an ultrasonic vibrating scalpel and with a regular scalpel. SETTING: Sprague-Dawley white rats (Charles River Canada Inc., St. Constant, Quebec, Canada) in a conventional laboratory setting. INTERVENTIONS: A standardized incision was performed on the uterine horn with a regular scalpel on one uterine horn and with an ultrasonic scalpel on the opposite horn. MAIN OUTCOME MEASURES: Degree of adhesions and histopathological changes of the uterine horns. RESULTS: The degree of adhesion formation was similar, but the uterine horn distal to the incision was dilated in most uterine horns that were incised with ultrasonic scalpel. The degree of coagulation necrosis was significantly higher 7 and 14 days after incision with an ultrasound scalpel than after incision with a regular scalpel. CONCLUSION: The use of an ultrasonic vibrating scalpel is associated with more tissue injury than that of a regular scalpel, but it does not produce more adhesion formation.

Animals↗

PubMed1989

A randomized comparative trial of carboplatin and iproplatin in advanced squamous carcinoma of the uterine cervix: a Gynecologic Oncology Group study.

A total of 394 patients with advanced, measurable squamous carcinoma of the uterine cervix and no prior chemotherapy were randomized to therapy with either carboplatin or iproplatin. There were 23 patients ineligible for the study and 10 patients who were not evaluable; the remaining 361 patients were evaluable for response and adverse effects. Randomization was well balanced for age, performance status, and prior therapy. Both platinum analogs were given every 28 days with starting doses of 400 mg/m2 for carboplatin (340 mg/m2 if the patient underwent prior radiation) and 270 mg/m2 for iproplatin (230 mg/m2 if the patient underwent prior radiation). These doses are equivalent to cisplatin doses of 75 to 100 mg/m2. Hematologic toxicity was dose-limiting, among which thrombocytopenia was slightly more common than leukopenia. Gastrointestinal toxicity was also prominent with both agents; however, iproplatin was significantly more toxic than carboplatin (P less than .001). Renal, otic, and peripheral nervous system toxicities were absent or infrequent with both analogs. No electrolyte abnormalities were observed. The percentage of planned dosages that were actually administered was 100% of carboplatin doses and 85% of iproplatin doses (P less than .0001). The reduction in iproplatin dose was apparently due to gastrointestinal toxicity. Response rates were similar for both agents (15% for carboplatin, 11% for iproplatin) and appear to be inferior to those noted with the parent compound, cisplatin.

Adult↗

PubMed1989

Vulvar intraepithelial neoplasia and skin appendage involvement.

Vulvar intraepithelial neoplasia may extend into the pilosebaceous units of the hairy and non-hairy skin of the vulva, and inadequate removal may cause treatment failure. We measured with a calibrated microscope the thickness of vulvar intraepithelial neoplasia and the depth to which it extended into the underlying pilosebaceous units of the vulvar skin. The mean thickness of vulvar intraepithelial neoplasia in 329 histologic sections from 62 cases was 0.38 mm; 99.5% of all vulvar intraepithelial neoplasia measured less than 0.77 and 0.69 mm in the hairy and non-hairy skin, respectively. Sebaceous-gland and hair-follicle involvement by vulvar intraepithelial neoplasia was 21 and 32%, respectively. The mean depth of sebaceous-gland involvement was 0.77 mm in the hairy skin and 0.50 mm in its non-hairy counterpart; 99.5% of all vulvar intraepithelial neoplasias extended less than 2.03 and 1.07 mm in the hairy and non-hairy skin, respectively. The mean depth of hair-follicle involvement was 1.04 mm; 99.5% of all hair follicles were involved less than 2.55 mm. Our findings suggest that removal of vulvar intraepithelial neoplasia to a depth of 1.0 and 2.0 mm in the non-hairy and hairy skin, respectively, is appropriate for successful treatment.

Adult↗

PubMed1987

Estrogen and progesterone receptor determination in the papillary cystic neoplasm of the pancreas. With immunohistochemical and ultrastructural observations.

Two cases of papillary cystic neoplasm (PCN) of the pancreas occurring in 18- and 34-year-old women are described. In both, the clinicopathologic features were typical. Immunohistochemical staining for neuron-specific enolase (NSE), S100 protein (S100), alpha-fetoprotein (AFP), carcinoembryonic antigen (CEA), and several peptide hormones was negative. Alpha-1-antitrypsin immunoreactivity was prominent, and its significance is discussed. Ultrastructural features were most compatible with partial acinar differentiation. Of the well-described cases of PCN, approximately 95% have occurred in women between the ages of 12 and 35, suggesting a role for hormonal factors in the pathogenesis of this tumor. Consequently, tumor tissue from one patient was assayed for estrogen and progesterone receptors: significant levels of high-affinity receptors were demonstrated for both hormones. Assays for the same receptors in five normal pancreases were negative. This constitutes the first reported measurement of these receptors in the PCN; the results indicate that the PCN may be another hormone-sensitive tumor.

Adolescent↗

PubMed1987

Hematologic monitoring in patients with cancer. A study of the Gynecologic Oncology Group.

A retrospective review of four Gynecologic Oncology Group protocols involving aggressive chemotherapy was carried out to assess the following. Whether granulocyte determinations, which require a differential count resulting in extra cost and time, added pertinent clinical information to that obtained from the white blood cell count alone. If, there is a predictable relationship between the white blood cell count and the platelet count as a reflection of bone marrow toxicity, and whether one can predict when maximum myelosuppression will occur during a treatment program. This data revealed that the white blood count and granulocyte levels are closely related; that rarely is life-threatening thrombocytopenia noted in the absence of leukopenia; and that myelosuppression can occur during any course of treatment and is not predictable. Thus, for these treatment regimens in gynecologic malignancies, the white blood count is sufficient for monitoring toxicity and adjusting future courses of chemotherapy. Only when the white blood count is severely depressed is it necessary to monitor the granulocyte and platelet counts.

Antineoplastic Combined Chemotherapy Protocols↗

PubMed1986

A phase II study of carboplatin in advanced squamous cell carcinoma of the cervix (a Gynecologic Oncology Group Study).

The Gynecologic Oncology Group conducted a Phase II trial of carboplatin in patients with measurable advanced squamous cell carcinoma of cervix. No prior therapy with cytotoxic drugs was permitted in patients entered into this study. Patients entered were GOG performance status 2 or better. Carboplatin 400 mg/m2 (340 mg/m2 in patients who had had prior pelvic radiotherapy with subsequent escalation to 400 mg/m2 if bone marrow tolerance was good) was administered as a 15-minute IV infusion. Treatments were repeated every four weeks until disease progressed or until toxicity prohibited further therapy. Thirty-nine evaluable patients were treated. Two complete and nine partial responses were observed (response rate 28.2%). No neurotoxicity and only mild reversible nephrotoxicity was seen. Gastrointestinal toxicity was severe in three patients (7.7%). Dose limiting toxicity was myelosuppression. Carboplatin is active against squamous cell carcinoma of cervix and appears to be less nephrotoxic, neurotoxic, and nauseogenic than cisplatin. Randomized studies of this drug against cisplatin are indicated to determine the role of carboplatin in the therapy of squamous cell carcinoma of cervix.

Anemia↗

PubMed1986

Expression of common acute lymphoblastic leukemia-associated antigen on germ cell tumor.

A mediastinal germ cell tumor is described that reacts with the anti-common acute lymphoblastic leukemia-associated antigen antibody J5 using both immunofluorescence and immunoperoxidase techniques. This antigen has been reported recently on various cell lines including melanoma, colon, and breast. It has also been seen on normal fibroblasts and peripheral granulocytes. This is believed to be the first description of a solid nonlymphoid neoplasm possessing this antigen, and the implications regarding prognosis and therapy are discussed.

Adult↗