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Biomedical subjects

W E Lucas

Publications and source records attributed to W E Lucas.

At least 19 recordsLinked to original sources
PubMed1991

A phase II trial of intraperitoneal cisplatin and etoposide as salvage treatment for minimal residual ovarian carcinoma.

We conducted a phase II study of intraperitoneal (IP) cisplatin (CDDP) and etoposide (VP-16) as salvage therapy in patients with ovarian cancer who had persistent disease or who had relapsed after primary systemic chemotherapy and had residual disease of less than 2 cm. Two hundred eleven courses of IP chemotherapy consisting of CDDP 200 mg/m2 and VP-16 350 mg/m2 were administered. All patients received intravenous (IV) thiosulfate protection. Treatment was given once every 4 weeks for a median of six cycles. Twenty-four of 37 assessable patients were clinically free of disease at the end of treatment (normal physical exam, computed tomographic [CT] scan, CA-125 and peritoneal cytology); one patient had a partial response. Ten of these 24 patients consented to reexploration at the end of treatment, and nine were in pathologic complete remission, while one patient had positive peritoneal washings as her only evidence of persistent disease. The median survival of the 37 patients was 26 months from the first day of IP treatment and 51 months from diagnosis. The major toxicity was myelosuppression, with median nadir WBC, granulocyte, and platelet counts of 2,400, 684, and 134,000/mm3, respectively. There was no cumulative renal damage, hypomagnesemia, or chemical peritonitis. We conclude that IP CDDP and VP-16 can produce pathologic complete remissions when used as a second-line regimen for patients with ovarian cancer who have received systemic cisplatin-based therapy and have less than 2 cm disease.

Adult↗
PubMed1990

A phase II trial of intraperitoneal cisplatin and etoposide for primary treatment of ovarian epithelial cancer.

We conducted a phase II trial of intraperitoneal (IP) cisplatin (DDP) and etoposide (VP-16) in stage III and IV newly diagnosed ovarian carcinoma patients with residual disease of any size. Twenty-three patients were entered, 19 had stage III and four stage IV disease. DDP 200 mg/m2 and VP-16 350 mg/m2 were given in 2 L saline IP via a Port-A-Cath (Pharmacia-Deltec, St Paul, MN). Sodium thiosulfate 4 g/m2 was given intravenously (IV) just before the start of IP instillation, and continued as a constant IV infusion of 2 g/m2/hr IV for a total of 6 hours. Treatment was given once every 4 weeks; six cycles of therapy were planned. Thirteen patients (56%) were in complete clinical remission at the end of treatment (normal physical exam, computed tomographic [CT] scan, CA-125, and peritoneal cytology). Seven of these 13 underwent a second-look laparotomy: three (13%) were in pathologic complete remission and four (17%) had microscopic disease only. Projected survival is 68% at 27 months, with 10 patients being alive and continuously free of disease. There was a very rapid fall in mean CA-125 to within normal limits at the end of the second course of treatment. The major toxicity was myelosuppression with median nadir WBC, granulocyte, and platelet counts of 2,600, 896, and 205,000/microL, respectively. There was no cumulative renal damage, anemia, hypomagnesemia, or chemical peritonitis. Neurotoxicity was similar to that observed with IV dosing. We conclude that therapy with the IP DDP/VP-16/IV thiosulfate regimen, in which all cytotoxic drugs are given only by the IP route, produces less anemia and renal damage than standard IV DDP-containing regimens, and that survival with this regimen appears to be at least as good as that produced by IV programs.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1989

Delayed erosion of intraperitoneal chemotherapy catheters into the bowel. Report of two cases.

Erosion of a silastic catheter into the small bowel occurred in two patients who previously had received multiple courses of uncomplicated intraperitoneal (IP) chemotherapy. Although bowel perforation is a recognized complication at the time of Tenckhoff catheter insertion, late erosion of the catheter into the bowel after its use for IP chemotherapy has not been previously reported. Catheter injection with radiographic contrast confirmed the diagnosis, evidence for which included nonspecific clinical findings of intraabdominal infection and pain during chemotherapy infusion.

Adult↗
PubMed1987

Phase I/pharmacokinetic study of intraperitoneal cisplatin and etoposide.

We administered cisplatin and etoposide by peritoneal dialysis to 39 patients with i.p. malignancies in order to investigate the toxicity, pharmacokinetics, and clinical activity of this 2-drug combination. All patients received i.v. sodium thiosulfate concurrently with the i.p. chemotherapy. Myelosuppression, nausea, vomiting, and malaise were the primary toxicities encountered. The maximum tolerated dose of etoposide was 350 mg/m2, when administered with a fixed dose of cisplatin, 200 mg/m2. Although the total (free and protein-bound) etoposide exposure for the peritoneal cavity was only 1.5-fold greater than that for the plasma, the free (non-protein bound) etoposide peritoneal exposure was 65-fold greater than the plasma. Tumor regressions were noted in patients with ovarian and pancreatic carcinomas. This study is the first demonstration of the large pharmacokinetic advantage that exists for the i.p. administration of highly protein-bound drugs, and it also documents the clinical activity of i.p. cisplatin and etoposide.

Abdomen↗
PubMed1987

Long-term survival of advanced refractory ovarian carcinoma patients with small-volume disease treated with intraperitoneal chemotherapy.

Ninety ovarian carcinoma patients failing primary intravenous (IV) combination chemotherapy were treated with cisplatin-based combination intraperitoneal therapy. Sixty-five patients had residual disease greater than 2 cm at the start of intraperitoneal therapy. Their median survival was 8 months. Twenty-five patients had disease less than 2 cm; their median survival was greater than 49 months, and the survival curve has an apparent plateau at 69%, with no relapses having occurred after 32 months. The median survival for all 90 patients was 15 months. The median duration of follow-up for all patients was 37 months. These results confirm the critical role of tumor bulk in determining the effectiveness of intraperitoneal therapy, and suggest a role for intraperitoneal salvage treatment in patients with small-volume disease.

Actuarial Analysis↗
PubMed1986

Adenocarcinoma of the uterine cervix.

Fifty patients with adenocarcinoma of the uterine cervix were evaluated retrospectively. Treatment was based on the stage and size of tumors and the overall medical condition of the patient. Radical surgery or surgery in combination with radiation therapy was employed whenever possible. The overall survival rate was 50%, with Stage IB survival 74%. Survival in Stage IB patients was adversely affected by increasing tumor grade and size. This closely correlated with a tendency of the tumors to dedifferentiate as they increased in size. Lymph node involvement increased with increasing grade of tumor as well. Survival in patients with advanced disease was dismal. Survival increased with aggressive management which should, if possible, include surgery in Stage I and II disease.

Adenocarcinoma↗
PubMed1986

Complications of extensive adhesion formation after intraperitoneal chemotherapy.

The results of modeling studies have suggested and clinical investigations have confirmed a major pharmacokinetic advantage for exposure of the peritoneal cavity to certain chemotherapeutic agents compared with exposure of the systemic circulation when these drugs are delivered through the intraperitoneal route. Objective antitumor responses and significant palliation of symptoms have been demonstrated. One major concern with the use of intraperitoneal therapy is the risk of inducing peritoneal sclerosis and extensive adhesion formation. At the University of California at San Diego (UCSD) Cancer Center, 115 patients with advanced intra-abdominal malignant conditions have been treated with several intraperitoneal chemotherapy programs. To date, with a total of 1,103 patient-months of follow-up study, seven episodes of small intestinal obstruction have developed of which two were definitely and five possibly related to chemotherapy induced adhesion formation. The development of methods to prevent or decrease peritoneal sclerosis will allow for greater application of this innovative therapeutic approach.

Adult↗
PubMed1985

Intraperitoneal chemotherapy for advanced ovarian cancer.

Treatment of patients with advanced ovarian cancer who have failure of first-line chemotherapy is rarely effective. Preliminary pharmacokinetic and phase II clinical studies established the feasibility of delivering relatively high concentrations of cisplatin intraperitoneally via a semipermanent catheter, while using intravenous sodium thiosulfate as a neutralizing agent to decrease the nephrotoxicity of cisplatin. Sixty patients with advanced ovarian cancer, all of whom had failure of first-line chemotherapy (including cisplatin in 56 of 60), were treated with high-dose intraperitoneal cisplatin in combination with doxorubicin and/or cytarabine. Of the 46 patients evaluable for response, 19 (42%) showed an objective response, most often (12/19) disappearance of malignant ascites. No serious drug-associated morbidity was observed aside from three cases of intestinal obstruction which may have been due in part to drug-induced adhesions. It is felt that prospective studies to compare the efficacy of intraperitoneal chemotherapy with other forms of "salvage" therapy, as well as its use as initial chemotherapy for advanced ovarian cancer, need to be done.

Altretamine↗
PubMed1985

Infectious peritonitis in patients receiving intraperitoneal chemotherapy.

A total of 32 episodes of infectious peritonitis developed in 90 patients receiving intraperitoneal chemotherapy. Staphylococcus epidermidis was the organism most commonly cultured, accounting for 65 percent of isolates. Result of initial gram stain was positive in 35 percent of cases. The development of fever and abdominal pain as well as rising peripheral and peritoneal fluid white blood cell counts was helpful in the making of a diagnosis of infectious peritonitis. Seventy-five percent of patients were cured with antibiotic therapy alone whereas one quarter also required removal of the semi-permanent catheter. Patients treated with intraperitoneal chemotherapy delivered by dialysis exchange over several days exhibited significantly more episodes of infection than patients treated by a single-drug instillation each month. Although the development of bacterial peritonitis remains a problem during intracavitary chemotherapy, the use of subcutaneous ports and meticulous sterile technique during catheter manipulation will hopefully decrease the risk of occurrence of this potentially avoidable complication.

Anti-Bacterial Agents↗
PubMed1985

The intraoperative intraperitoneal administration of cisplatin: a case report.

A 63-year-old female with endometrial carcinoma who had received prior extensive systemic chemotherapy and pelvic radiotherapy was administered intraoperative cisplatin (100 mg/m2) by the i.p. route. The method and timing of chemotherapy administration were chosen to optimize delivery of the antineoplastic agent to tumor remaining following debulking surgery. There was no evidence of excessive or unexpected local or systemic toxicity. The intraoperative i.p. instillation of chemotherapeutic agents has the theoretical potential of improving to a limited degree the problem of insuring adequate drug distribution over i.p. chemotherapy.

Cisplatin↗
PubMed1985

Intraperitoneal chemotherapy with high-dose cisplatin and cytosine arabinoside for refractory ovarian carcinoma and other malignancies principally involving the peritoneal cavity.

Sixty-two patients with refractory ovarian carcinoma or other malignancies principally confined to the peritoneal cavity were treated with an intraperitoneal combination chemotherapy regimen consisting of cisplatin (100 mg/m2 or 200 mg/m2) and cytosine arabinoside (4 X 10(-3) mol/L or 10(-2) mol/L). Sodium thiosulfate was simultaneously administered intravenously (IV) to protect against cisplatin-induced nephrotoxicity. Sixteen of 52 evaluable patients demonstrated evidence of a clinical response including 14 (36%) of 39 with refractory ovarian carcinoma. Systemic toxicity was not severe except for cisplatin-induced emesis and a single episode of major renal insufficiency. Dose-limiting toxicity was bone marrow suppression with cytosine arabinoside administered at 10(-2) mol/L. We conclude that combination intraperitoneal therapy with high-dose cisplatin and cytosine arbinoside can be safely administered with objective tumor responses observed in patients with ovarian carcinoma refractory to front-line chemotherapy and in occassional individuals with other malignancies principally confined to the peritoneal cavity.

Adult↗
PubMed1984

Totally implantable system for peritoneal access.

A totally implantable system for providing access to the peritoneal cavity was evaluated. Fifty-six Port-A-Cath (Pharmacia Nu Tech, Piscataway, NJ) peritoneal access systems were implanted in 54 cancer patients receiving intraperitoneal chemotherapy. The catheters are accessed by transcutaneous placement of a Huber point needle through a silicone septum at the top of the portal. A total of 32 patient years of experience are reported. The Port-A-Caths have been in place for a median of 22 weeks (range, one to 85). A total of 401 entries have been made for paracentesis, chemotherapy administration, antibiotic administration, peritoneal lavage for cytology, and catheter flushing. There have been six episodes of peritonitis (five Staphylococcus epidermidis, one S aureus) in three patients. There have been no mechanical failures of the Port-A-Caths. Loss of bidirectional flow through the catheter due to fibrin deposition about the catheter has been the major cause of catheter failure. Patient acceptance of the Port-A-Cath has been excellent.

Antineoplastic Agents↗
PubMed1984

Combination intraperitoneal chemotherapy with cisplatin, cytarabine, and doxorubicin for refractory ovarian carcinoma and other malignancies principally confined to the peritoneal cavity.

Thirty-one patients with refractory ovarian cancer and other malignancies principally confined to the abdominal cavity were treated with an intraperitoneal combination-chemotherapy regimen consisting of cisplatin (100 to 200 mg/m2), cytosine arabinoside (10(-4) to 10(-3) mol/L) and doxorubicin (2 to 18 mumol/L). Sodium thiosulfate was simultaneously administered intravenously to prevent cisplatin-induced nephrotoxicity. Eight of 26 evaluable patients demonstrated clinical response including seven of 17 (41%) with ovarian cancer refractory to frontline chemotherapy. Systemic toxicity was mild except for nausea and vomiting. Abdominal pain secondary to doxorubicin was the major complication of therapy. We conclude that combination intraperitoneal therapy with cisplatin, cytosine arabinoside, and doxorubicin can be safely administered with objective tumor responses observed in patients with ovarian cancer heavily pretreated and in individuals with other malignancies involving the peritoneal cavity. Doxorubicin-induced local pain limits the ability to administer multiple courses of this treatment regimen.

Adult↗
PubMed1983

Superficially invasive vulvar cancer with nodal metastases.

Seven patients with superficially invasive vulvar cancer and lymph node metastases are reported. Histology of the primary tumor does not seem to correlate reliably with its metastatic potential in any individual case, though "spray," pseudoglandular, and small cell carcinomas may be particularly aggressive lesions. While wide local excision seems to be adequate treatment for the primary lesion, it is recommended that for lesions with greater than 1 mm of stromal invasion, bilateral inguinal-femoral lymphadenectomy should be performed for midline lesions, and at least ipsilateral inguinal-femoral lymphadenectomy should be performed for lateralized lesions.

Adult↗
PubMed1982

Intraperitoneal cisplatin with systemic thiosulfate protection.

Seventeen patients with intraperitoneal tumors were treated by 4-hour intraperitoneal dialysis with cisplatin alone, or in combination with an intravenous neutralizing agent, sodium thiosulfate. Cisplatin alone, 90 mg/m2 body surface area intraperitoneally, produced nephrotoxicity. When intraperitoneal cisplatin therapy was combined with intravenous thiosulfate treatment, the dose of cisplatin could be escalated to 270 mg/m2 body surface area without causing an increase in serum creatinine levels or undue myelosuppression. Even at doses up to 270 mg/m2, no local toxicity occurred. The peak peritoneal concentration of free reactive cisplatin averaged 21-fold higher than the plasma level, and the area under the peritoneal cisplatin elimination curve averaged 12-fold more than the area under the plasma curve. Neither of these ratios varied significantly with cisplatin dose. Regression of intraperitoneal tumor masses was observed in patients with far-advanced ovarian carcinoma, mesothelioma, and malignant carcinoid.

Adult↗
PubMed1981

Estrogen--a cause of gynecologic cancer?

For many years before the first case-control studies showing an increased risk of endometrial cancer among menopausal estrogen users were published, a considerable body of circumstantial evidence accumulated suggesting a tumor-promoting role for estrogens in specific target organs. In regard to endometrial cancer, an "estrogen hypothesis" has evolved based on observations such as an increased incidence of endometrial cancer in patients with chronic anovulation and in patients with estrogen-secreting ovarian tumors; development of endometrial cancer in certain estrogen treated animals; and successful treatment of some metastatic endometrial cancer with progesterone. Since 1975, a number of case-control studies have appeared relating estrogen treatment of menopausal women to a rising incidence of endometrial cancer. The same cannot be said, with a few exceptions, of studies of breast and ovarian cancer. An understanding of the physiology of the estrogens, particularly in obese women, aids in understanding the possible role of estrogen in promoting endometrial neoplasia. Although the case for estrogens promoting some forms of endometrial cancer is strong, at the present time it cannot unequivocally be stated that estrogens cause any form of cancer in humans.

Carcinogens↗
PubMed1981

Preoperative whole pelvic external irradiation in stage I endometrial cancer.

Between 1966 and 1978, 201 patients with adenocarcinoma of the endometrium were treated at two hospitals in San Diego. Of these patients, 161 had disease limited to the corpus at the time of diagnosis. The majority of these patients received external whole-pelvic irradiation, followed as soon as possible by simple extrafascial hysterectomy and bilateral salpingo-oophorectomy. When this treatment method was used, actuarial survivals of 95% for Stage I disease were achieved. Also reported is the low incidence of wound complications in the group of patients operated soon after cessation of irradiation. The patients treated in this fashion had good survival rates, little morbidity from the adjunctive irradiation, and fewer wound complications than previously anticipated.

Adenocarcinoma↗