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BACKGROUND This study was designed to determine the feasibility, maximum tolerated dose, and toxicities of intraarterial administration of paclitaxel-albumin nanoparticles in patients with advanced head and neck and recurrent anal canal squamous cell carcinoma. Antitumor activity also was assessed. METHODS Forty-three patients (31 with advanced head and neck and 12 with recurrent anal canal squamous cell carcinoma) were treated intraarterially with ABI-007 every 4 weeks for 3 cycles. In total, 120 treatment cycles were completed, 86 in patients with head and neck carcinoma (median, 3 cycles; range, 1–4) and 34 in patients with anal canal carcinoma (median, 3 cycles; range, 1–4). ABI-007 was compared preliminarily with Taxol® for in vitro cytostatic activity. Increasing dose levels from 120 to 300 mg/m2 were studied in 18 patients. Pharmacokinetic profiles after intraarterial administration were obtained in a restricted number of patients. RESULTS The dose-limiting toxicity of ABI-007 was myelosuppression consisting of Grade 4 neutropenia in 3 patients. Nonhematologic toxicities included total alopecia (30 patients), gastrointestinal toxicity (3 patients, Grade 2), skin toxicity (5 patients, Grade 2), neurologic toxicity (4 patients, Grade 2) ocular toxicity (1 patient, Grade 2), flu-like syndrome (7 patients, Grade 2; 1 patient, Grade 3). In total, 120 transfemoral, percutaneous catheterization procedure–related complications occurred only during catheterization of the neck vessels in 3 patients (2 TIA, 1 hemiparesis) and resolved spontaneously. CONCLUSIONS Intraarterial administration of ABI-007 by percutaneous catheterization does not require premedication, is easy and reproducible, and has acceptable toxicity. The maximum tolerated dose in a single administration was 270 mg/m2. Most dose levels showed considerable antitumor activity (42 assessable patients with 80.9% complete response and partial response). The recommended Phase II dose is 230 mg/m2 every 3 weeks. Cancer 2001;92:2592–602. © 2001 American Cancer Society.

Complete and lasting control of diffuse metastases from a renal cell carcinoma has been achieved by automatic continuous infusion of a single cytotoxic agent, fluorodeoxyuridine (FUDR). A patient with a single brain metastasis from renal cell carcinoma developed pulmonary, mediastinal, and retroperitoneal metastases after radical nephrectomy. A Medtronic Synchromed pump (Medtronic Inc., Minneapolis, MN) was implanted for the circadian systemic infusion of FUDR in 14-day courses with 14-day drug-free intervals. A complete response (CR) at all sites, was obtained in 3 months, and maintained for 22 months. After a second brain metastasis, treated by radiation therapy and cisplatin as radiosensitizer, a CR was obtained again and is now of 31 months' duration, which is four times the record to date. The overall hospitalization was 2 days. Acceptance of the pump is excellent and it functions precisely and reliably. This case should stimulate greater interest in techniques of automatic continuous infusion of cytostatics, given its greater efficacy and lower toxicity.

From 1986 to 1988, 35 patients with a hepatoma judged either inoperable or unresectable because of coexistent cirrhosis were treated with hepatic arterial embolization of mitomycin C microcapsules. Five of these 35 patients (14.5%) could not be treated because of inability to selectively cannulate the hepatic artery and were therefore excluded from the evaluation (feasibility rate, 86%). There were 24 men and six women with a median age of 57 years (range, 47 to 79) who could be classified as Okuda I (14 pts) or Okuda II (16 pts) and Child Class A:18 and Child Class B:12 in the remaining patients. A median dose of 0.5 mg mitomycin C/kg was administered to each subject and the treatment was repeated at 5 to 6 week intervals. Seventy courses were administered to these 30 patients (median, two courses/patient; range, 1 to 4). Minor complications were frequent (63%) but always either resolved spontaneously or after appropriate medical treatment. Neither severe renal nor hepatic toxicity was observed. No specific treatment related mortality was observed. When alpha-fetoprotein levels and tumor volume were assessed to evaluate the response to treatment using established criteria for identifying a response, an objective response was found in 43% of the cases treated. The actuarial median survival was 7 months and the 1-year actuarial survival was 36% (51% for those rated as Child Class A and 0% for those identified as Child Class B, P = 0.04 and 78% rated as Okuda Types I and 0% Okuda type II, P = 0.0001). The excellent quality of life and the increased survival rate experienced after mitomycin C microcapsule embolization suggest that this treatment modality can be used successfully in patients seen in the West who have unresectable hepatoma.

The authors treated 42 metastatic renal cell carcinoma (RCC) patients who had received no previous chemotherapy or radiation therapy with circadian venous continuous infusion of 5-fluoro-2-deoxyuridine (FUDR). The drug was delivered by Medtronic Synchromed implantable pump (Medtronic, Inc., Minneapolis, MN) in 14-day cycles alternating with 14-day intervals of heparinized physiologic saline infusion. In the course of 24 months 444 cycles of therapy have been given for a total of 12449 days of pump function. Of the patients observed for at least 3 months (range, 3 to 23 months; median, 7 months) three showed complete response (7%; 95% confidence interval, 0% to 15%), three partial response (7%; confidence interval, 0% to 15%), 18 stable disease, and 18 showed progression. Eighteen patients, all with advanced disease at the time of implantation, were living 6 months after treatment started. Circadian continuous central venous infusion of FUDR is minimally toxic. The FUDR can be delivered safely and conveniently in this way for long spans. This therapy is as active as any currently available treatment, is administered in an entirely outpatient setting, and is associated with a normal quality of life.

Complete and lasting control of diffuse metastases from a renal cell carcinoma has been achieved by automatic continuous infusion of a single cytotoxic agent, fluorodeoxyuridine (FUDR). A patient with a single brain metastasis from renal cell carcinoma developed pulmonary, mediastinal, and retroperitoneal metastases after radical nephrectomy. A Medtronic Synchromed pump (Medtronic Inc., Minneapolis, MN) was implanted for the circadian systemic infusion of FUDR in 14-day courses with 14-day drug-free intervals. A complete response (CR) at all sites, was obtained in 3 months, and maintained for 22 months. After a second brain metastasis, treated by radiation therapy and cisplatin as radiosensitizer, a CR was obtained again and is now of 31 months' duration, which is four times the record to date. The overall hospitalization was 2 days. Acceptance of the pump is excellent and it functions precisely and reliably. This case should stimulate greater interest in techniques of automatic continuous infusion of cytostatics, given its greater efficacy and lower toxicity.

From 1986 to 1988, 35 patients with a hepatoma judged either inoperable or unresectable because of coexistent cirrhosis were treated with hepatic arterial embolization of mitomycin C microcapsules. Five of these 35 patients (14.5%) could not be treated because of inability to selectively cannulate the hepatic artery and were therefore excluded from the evaluation (feasibility rate, 86%). There were 24 men and six women with a median age of 57 years (range, 47 to 79) who could be classified as Okuda I (14 pts) or Okuda II (16 pts) and Child Class A:18 and Child Class B:12 in the remaining patients. A median dose of 0.5 mg mitomycin C/kg was administered to each subject and the treatment was repeated at 5 to 6 week intervals. Seventy courses were administered to these 30 patients (median, two courses/patient; range, 1 to 4). Minor complications were frequent (63%) but always either resolved spontaneously or after appropriate medical treatment. Neither severe renal nor hepatic toxicity was observed. No specific treatment related mortality was observed. When alpha-fetoprotein levels and tumor volume were assessed to evaluate the response to treatment using established criteria for identifying a response, an objective response was found in 43% of the cases treated. The actuarial median survival was 7 months and the 1-year actuarial survival was 36% (51% for those rated as Child Class A and 0% for those identified as Child Class B, P = 0.04 and 78% rated as Okuda Types I and 0% Okuda type II, P = 0.0001). The excellent quality of life and the increased survival rate experienced after mitomycin C microcapsule embolization suggest that this treatment modality can be used successfully in patients seen in the West who have unresectable hepatoma.

From 1967 to 1970, 94 children ranging in age from 15 months to 15 years underwent lower limb lymphography with Lipiodol Ultra Fluide. While 63.8% of patients had either Hodgkin's disease (31 cases) or lymphoreticular sarcomas (29 cases), 36.2% of the children had different types of solid tumors (32 cases). In almost every patient, the procedure was performed bilaterally and without difficulty. There were no significant side effects. Lymphograms were positive in 45.9% of the cases; some of the cases were controlled with surgery. The importance of lymphography in also determining the clinical stage in children with malignant lymphoma is emphasized. In solid tumors, the number of our patients is not yet sufficient to draw definite conclusions. However, positive lymphograms were observed in 10 of 11 patients with neuroblastoma, in 3 of 4 with rhabdomyosarcoma, and in 2 of 3 with Ewing's sarcoma. The possibility that the initial spread of these diseases could also occur through the lymphatic pathway is discussed.