Intra-arterial chemotherapy for unresectable pancreatic cancer.

BACKGROUND: A phase II trial of a new intra-arterial chemotherapy regimen for unresectable pancreatic cancer (UPC). PATIENTS AND METHODS: Ninety-six patients with UPC were treated with intra-arterial chemotherapy at three-weekly intervals. The schedule used was FLEC: 5-fluorouracil 1000 mg/m2, folinic acid 100 mg/m2, carboplatin 300 mg/m2; epirubicin 60 mg/m2. RESULTS: The overall response rates by CT-scan evaluation were: 15% partial response (PR), 44% stable disease (SD), 17% progressive disease (PD). The overall median survival was 9.9 months, and 10.6 and 6.8 for UICC stage III and IV, respectively. Pain reduction occurred in 42% of patients. A weight gain > 7% from baseline occurred in 8% of patients. A total of 341 courses of FLEC were administered. Grade 3-4 hematological toxicity was seen in 25% of patients; ematemesis in 4%; grade 3 gastrointestinal toxicity in 3%; and grade 3 alopecia in 16%. One sudden death, a pre-infarction angina, and a transitory ischemic attack were observed. The only complication related to the angiographic procedure was an intimal dissection of the iliac artery. CONCLUSIONS: The intra-arterial FLEC regimen was well tolerated and active. It requires only one day of hospitalization. Efficacy could only be assessed in a randomized study against a gemcitabine containing regimen.

Isolated hyperthermia chemotherapy perfusion for limb melanoma.

Safe techniques for regional chemotherapy of the limbs by perfusion are now available. The method is effective in obtaining regionally confined high levels of toxic drugs or chemotherapeutic agents in the isolated areas. The best responses have been observed in limb melanoma with recurrent or intransit disease. Chemotherapy by perfusion as an adjunct to surgical excision reduces the local recurrence and the regional and lymph node metastases. Our survivals for adjunctive perfusion for Stage I melanomas with Level V and lesions 5 mm thick and thicker are better than usually reported. Regional chemotherapy has had an important role in reduction of major amputations for the control of limb melanoma. Multiple chemotherapeutic limb perfusions can further extent survival in patients with recurring melanoma.

Malignant melanoma in American black females: an unusual distribution of primary sites.

BACKGROUND: Since the inception of the Charity Hospital Tumor Registry in 1948, 80 cases of malignant melanoma in blacks were treated at the Tulane University School of Medicine, Department of Surgery. Among black people, melanoma occurs on acral dermal sites. The histologic type is primarily acrallentiginous melanoma (ALM), found on acral, volar-subungual skin and junctional mucocutaneous sites. STUDY DESIGN: The registry records of 80 black patients with malignant melanoma were reviewed. The clinical data for 41 female patients were compared to those of 39 male patients. These data were analyzed according to the sex of the patient as well as the histologic type, site, and stage of disease at diagnosis. RESULTS: Among women, 44 percent of primary lesions were found on extradermal sites compared with only 10 percent among men. Only 32 percent of primary lesions among women were located on the foot, whereas 73 percent of the primary lesions in men were found on the foot. Of the seven patients with vulvar, cervical, and vaginal melanoma, none lived more than two years after diagnosis. Two female patients with anorectal melanoma succumbed to their disease within 22 months. However, 50 percent of the female patients with head and neck lesions and 75 percent of those with eye lesions lived more than five years. Forty and 26 percent of the female patients with limb lesions lived five and ten years, respectively. CONCLUSIONS: Black females have a higher rate of extracutaneous melanoma than black men or white men and women, which accounts for a distinct negative impact on survival rates among black women with melanoma. In addition, the worst prognosis of melanoma among black women is not entirely related to delays in diagnosis, as has been suggested, but to their higher rates of extracutaneous melanoma.

Regional chemotherapy for inoperable pancreatic carcinoma.

BACKGROUND: Survival for adenocarcinoma of the pancreatic remains unchanged over the last two decades. The majority of patients (85%) are diagnosed with an inoperable tumor. Patterns of failure reveal that pancreatic cancer involves three compartments: the pancreatic bed and regional lymph nodes, the liver and the peritoneal surfaces. Twelve patients with advanced, unresectable pancreatic cancer, Stage II/III, were treated with regional intra-arterial chemotherapy and extracorporeal hemofiltration directed towards the pancreatic tumor-bearing area and the liver. METHODS: Five patients had an arterial catheter/port system placed within the celiac axis; the rest had an angiographically placed arterial catheter. All patients had a 16 Fr PFM filtration catheter inserted in the vena cava positioning the tip at the level of the diaphragm and then connected to a hemofiltration unit. Mitomycin C was infused over 25 minutes followed by 5-FU over 10 minutes. The hemofiltration was begun before the drug infusion and continued for 70 minutes. The twelve patients underwent 33 cycles of regional chemotherapy plus hemofiltration. RESULTS: Five patients had a partial response (45.5%), five had stable disease (45.5%), and one had progression (9%). Four patients were re-explored with one patient undergoing a curative resection. The average survival for patients with unresectable pancreatic adenocarcinoma is 13 months. Tumor implantation and progression on the peritoneal surfaces remains the major site of treatment failure. CONCLUSIONS: Regional chemotherapy plus hemofiltration with MMC and 5-FU appears to improve the response of Stage II/III inoperable pancreatic cancer and can convert some patients to resectability without significant complications and with no mortality.

Regional chemotherapy with hemofiltration: a rationale for a different treatment approach to advanced pancreatic cancer.

BACKGROUND/AIMS: Since 1989, thirty-two patients with advanced, intra-abdominal pancreatic cancer were treated with regional chemotherapy in combination with extracorporeal hemofiltration. PATIENTS AND METHODS: Eleven patients had locally advanced, unresectable cancer, and ten had advanced disease with liver metastases. Three patients had developed liver metastases following a radical resection. One patient had an incomplete resection with local residual disease, and a second had developed a local recurrence after a radical resection. One patient had an unresectable cystadenocarcinoma. Five patients had failed prior systemic therapies for unresectable pancreatic cancer. The patients underwent 85 treatments with regional chemotherapy plus hemofiltration, an average of 2.7 treatments per patient. RESULTS: Of 21 patients treated primarily with regional chemotherapy plus hemofiltration, there were two complete responses (9%) and eight partial responses (38%), an overall total response rate of 47%. The average survival for patients with Stage II/III localized, unresectable disease is 13 months and that for Stage IV unresectable disease with liver metastases is 9 months. CONCLUSIONS: Patients with recurrent disease following a radical resection or having failed prior systemic therapies generally had no benefit from regional chemotherapy plus hemofiltration.

Primary non-Hodgkin's lymphoma of the duodenum.

Primary non-Hodgkin's lymphoma of the duodenum is an uncommon primary tumor of the gastrointestinal (GI) tract. Diffuse, large cell lymphoma of B-cell origin is currently recognized as representing the predominant histologic type of primary extranodal lymphoma arising in a gastrointestinal site. Three patients are presented with primary lymphoma arising in the second (two) and fourth (one) portions of the duodenum. Two patients with Stage I-E disease were treated by pancreaticoduodenectomy followed by postoperative radiotherapy, and remain without recurrence at 8 and 6 years. A third patient with Stage II-E disease of the fourth portion of the duodenum was treated with total resection of all bulky disease followed by chemotherapy without radiotherapy. However, this patient died after 46 months. The literature is reviewed, with emphasis on the use of surgical resection in the treatment of non-Hodgkin's lymphoma of the duodenum.

Regional chemotherapy for melanoma. A 35-year experience.

OBJECTIVE: The authors present their 35-year experience with intra-arterial chemotherapeutic regional perfusion of 1139 patients with melanomas, using an extracorporeal oxygenated circuit and heart-lung apparatus. SUMMARY BACKGROUND DATA: Intra-arterial chemotherapy produces improved responses in many tumors. By isolating and sustaining the area with extracorporeal oxygenated circulation, high doses can be delivered to the tumor area, limited only by local toxicity. Drug levels up to 10 times those achieved by systemic administration are obtained. METHODS: Techniques for hyperthermic perfusion were developed for limbs, pelvis, head, neck, and skin of the breast. Melphalan (Burroughs Wellcome, Research Triangle Park, NC) was used in 753 patients. Combinations with melphalan or other drugs were used in remaining cases at temperature of 38 to 40 C for 30 to 60 minutes. RESULTS: Chemotherapy perfusion followed by tumor excision or node dissection, was performed where indicated. The cumulative 10-year survival for patients with localized melanomas was 70%. For patients with local recurrences or satellites within 3 cm, survival was 61%. For those with regionally confined intransit tumors, survival was 30%; for those with regional node involvement, 38%; for those with intransit and nodal metastases, 16%; for those with distant metastases and perfusion--mainly to save functional limbs--survival was 7%. Multiple perfusions were performed in 158 patients with recurrent disease on 366 occasions. Patients with indolent regionally confined melanomas were benefited by prolongation of useful life. CONCLUSIONS: Safe perfusion techniques are available for most anatomic regions. Increased chemotherapeutic doses are delivered to isolated areas limited only by local toxicity. Adjunct perfusion in poor prognosis stage I cases is useful in reducing local recurrence, and intransit or lymph node metastases. Regional perfusion reduces the need for major amputation. Multiple perfusion can be useful in treating recurrent chronic melanoma.

Multiple perfusions for melanoma.

From 1957 to 1992, 1139 patients had regional perfusion alone, or combined with excisional surgery for malignant melanoma. Of these, 158 patients had multiple perfusions for recurrent disease, including 155 for limb melanoma and three for head and neck melanoma. One-hundred-and-twenty patients were perfused twice, 28 treated three times, eight treated four times, and two treated five times. At first perfusion, 39 patients were classified as disease stages I and II, 98 at stage III, and 21 at stage IV. Melphalan was used in 70% of perfusions, either alone or in combination. Nitrogen mustard was used sparingly in only a few patients. Fifty-one patients with stage III disease had the greatest number of perfusions (127). Cumulative survival from date of first perfusion at 5 and 10 years were: stage 1,68 and 36%; stage IIIA, 25 and 16%; stage IIIB, 32 and 10%; stage IIIAB, 29 and 11% and stage IV, 14 and 0%. When compared with the entire series, the percent survival was decreased by 2 to 3 times, however, 21 patients remain alive and disease-free. For stages I and II, patients are alive and disease-free from 5 to 33 years. For stage IIIA, 6 patients were alive at the last follow-up, however, the status of two are currently unknown. For stage IIIB survival times range from 8 to 106 months with two patients alive without recurrence. For stage IIIAB, two patients are alive and disease-free at 15 and 26 years.(ABSTRACT TRUNCATED AT 250 WORDS)

Acral lentiginous melanoma.

Between 1958 and 1990, 82 patients with acral lentiginous melanoma were treated by the Tulane Surgical Service with regional perfusion, excision of lesion, and lymph node dissection. The patient group comprised 27 white men, 29 white women, 18 black men, and 8 black women, with an average age of 61 years. More foot lesions than hand lesions were reported, and all the lack men had foot lesions. In stage I patients, overall 5-year survival rates were 65% at 5 years and 44% at 10 years, with differences by race and gender. The black men did poorest, with a 13% 10-year survival rate. Survival rates were worse with increasing disease stage when calculated using univariate analysis. The 5-year survival rate of all patients with stage III and stage IV disease was 26%. A multivariate analysis was performed in 78 of 82 patients in whom all variables of Clark's level, age, race, stage, and sex were known. A strong relationship was observed between decreasing survival time and increasing Clark's level, with stage of marginal significance. In a multivariate analysis of patients with stage I disease, an increasing level of invasion was found to be significant, with a trend for a relationship to thickness. A trend toward decreased survival time was observed in men and blacks.

Vaginal melanoma and the role of regional chemotherapy.

Vaginal melanoma is a rare cancer usually diagnosed as a locally advanced disease. Aggressive surgical management of the primary tumor and local-regional recurrences, combined with the use of adjuvant radiation and chemotherapy, improves disease-free interval and, perhaps, survival times. Techniques of regional chemotherapy allow the delivery of high doses of chemotherapy to the tumor bed, while minimizing systemic toxicities. These treatments can be used to decrease tumor size, render bulky tumors resectable, and decrease the need for radical procedures. Additionally, they may help eradicate clinically inapparent local-regional disease and have a favorable effect on survival times.

Treatment of abdominal malignant neoplasms using regional chemotherapy with hemofiltration.

The regional delivery of high-dose chemotherapy for malignant neoplasms of the limb with the isolated regional perfusion technique was first described in the late 1950s. Recently, the use of concomitant hemofiltration for rapid systemic drug removal permits the use of higher regional drug levels in treating patients with advanced abdominal malignant neoplasms without complete vascular isolation. Twenty-five patients successfully underwent 42 treatments of high-dose intra-arterial chemotherapy with concomitant hemofiltration at Tulane University Medical Center Hospital, New Orleans, La, from 1989 through 1990. One patient (4%) achieved a complete response. Two patients (8%) had partial responses following high-dose intra-arterial chemotherapy with concomitant hemofiltration and their residual disease was resected for cure. Seven patients (28%) achieved a partial response, 11 (44%) had stable disease, and four (16%) had progression of disease.

Regional perfusion for the treatment of subungual melanoma.

Thirty-one patients with subungual melanoma representing 2.6 per cent of all patients with limb melanoma were treated by isolated regional perfusion. Acral lentiginous melanoma prevalent on subungual and volar skin was the most common histologic type. The subungual lesions primarily occurred on the lower limbs (61%) and great toe (48%). At diagnosis, most patients had advanced disease; 53 per cent of stage I patients had lesions with level IV invasion or greater. The median thickness of the primary lesion was 2.35 mm. All patients were treated by isolated regional perfusion and amputation of the involved digit, as well as regional lymph-node dissection where clinically indicated. The mean survival rate for all stages at five years was 35 per cent. Patients with stage I disease had the best survival rates, 61 per cent at five years and 54 per cent at ten years; however, patients with advanced disease, stage III (M.D. Anderson classification), had only a 17 per cent survival rate at five years and 8 per cent at 10 years. Women had slightly better survival rates than men, and patients with upper-limb lesions had the better prognosis.

Deep vein thrombophlebitis and pulmonary embolism in patients with malignant gliomas.

Patients with malignant gliomas are at increased risk for deep vein thrombophlebitis (DVT) and pulmonary embolism (PE). Difficult anticoagulation in cancer patients undergoing surgery, chemotherapy, or radiotherapy limit the choices of therapy for DVT. Interruption of the inferior vena cava with a Greenfield filter is a safe method of treating patients who have malignant gliomas and DVT with PE. We studied 23 patients treated for malignant gliomas; 16 were men and seven were women, with a mean age of 51 years (range, 26 to 78). Five patients had DVT shown by noninvasive blood flow studies, and four subsequently had PE, as demonstrated by ventilation perfusion lung scan; in one patient PE was diagnosed at autopsy. Of the 23 patients, four with postoperative craniotomy had DVT and all four had PE. Two of the five patients who received preoperative chemotherapy had DVT and three had PE. All patients with PE had a Greenfield filter placed in the inferior vena cava via the internal jugular vein without adverse sequelae.

Isolated regional perfusion for treatment of limb melanoma in the American black.

Since 1957, 961 patients with invasive malignant melanoma of the limbs were treated by regional perfusion. Forty-eight patients were black, representing 5 per cent of all patients with regional melanoma treated during this period. Thirty-one of the 48 patients were men, and 17 were women. Only 21 of the 48 patients had stage I lesions (M.D. Anderson classification), of whom 63 per cent had level IV or greater invasion. The average depth of invasion was 3.70 mm. Of 21 patients with stage III disease, 15 came to diagnosis with an intact primary lesion in addition to regional disease, and the majority of lesions arose on a plantar site with level V invasion. Eighty per cent of the patients had acral lentiginous melanoma. All melanoma patients were treated by isolated regional perfusion with wide excision of the primary plus regional lymph node dissection for biopsy-proven regional disease. At 10 years, survival rates were 71 per cent for stage I patients and 12.5 per cent for those with stage III disease. When black patients having had acral melanoma on a plantar or palmar site were compared with white patients of a similar stage of disease, however, it was found that black patients had equivalent long-term survival rates.

Surgical management of unresectable retroperitoneal leiomyosarcomas.

Retroperitoneal leiomyosarcomas are rare tumors with a poor prognosis. These tumors are often deemed unresectable because of their large size when diagnosed. This study presents two recent patients who show that retroperitoneal leiomyosarcomas can be resected successfully. Adjuvant radiotherapy is useful in treatment of patients with residual disease. Although the contribution of chemotherapy in prophylaxis and treatment of these tumors remains undefined, various chemotherapeutic regimens are currently under investigation.

Chemotherapy by regional perfusion for limb melanoma.

The administration of chemotherapy by isolated regional perfusion was developed in 1957 at Tulane University and was found to be of greatest benefit for patient with melanoma of the limbs. From 1957 to 1984, 897 patients were treated by this method. The 10-year survival rate for 831 patients with primary melanoma was 77 per cent. Women survived longer than men, with 10-year rates of 81 per cent and 65 per cent, respectively. Prophylactic lymph node dissection was of benefit for males with poor prognosis distal lower limb lesions, but other groups did not benefit. Primary lesions on the arm and thigh did better than lesions of the hand or foot, with plantar and subungual lesions having the least favorable results. Thickness, level, and histologic type were also significant prognostic indicators. Thirty-three patients with locally recurrent melanoma (stage II) treated by perfusion and excision had a 10-year survival rate of 59 per cent. For 129 patients with metastases to the regional lymph nodes (IIIB), perfusion plus RLND produced a 10-year rate of 51 per cent; survival rates for those with a single positive node was 64 per cent. Seventy patients with satellitosis or intransit metastases (IIIA) had a 10-year survival rate of 23 per cent. Thirty-eight patients with metastases to limbs from unknown primaries had a 10-year survival rate of 52 per cent. The overall 10-year rate for all stage III patients was 41 per cent. Perfusion produced useful palliation in 144 patients with limb melanoma in the presence of systemic metastases.

Noninvasive evaluation of peripheral vasculature following regional hyperthermic chemotherapeutic perfusion (RHCP).

Regional hyperthermic chemotherapeutic perfusion (RHCP) has been used to treat over 1000 patients with advanced melanoma and soft tissue sarcoma. This study analyzes the impact of RHCP on the peripheral vasculature. Forty-one patients (23 women, 18 men) with an average age of 51.3 years were treated by RHCP of an upper or lower extremity using phenyalanine mustard for 60 minutes at a mean extremity temperature of 40 C. Patients were examined preoperatively and postoperatively at 36 hours, 7 days, 1 month, and 6 months by noninvasive arterial (Doppler-resting analog velocity waveform, response to stress) and venous (Doppler, impedance plethysmography [IPG], phleborrheography [PRG]) measurements. Upper-extremity evaluation of 14 patients (9 women, 5 men) indicated no abnormal studies. Response to stress showed an increase of the brachial:distal vessel ratio of 0.1 +/- 0.05; tendency of the analog velocity waveform toward triphasic; and response to stress augmented by 0.18 +/- .03 at 36 hours. Lower-extremity evaluation of 27 patients (15 women, 12 men) indicated two with thrombophlebitis. Response to stress showed an increase of the ankle: brachial ratio of .016 +/- 0.04; change in the analog velocity waveform toward triphasic; and response to stress augmented by 0.08 +/- 0.08 at 36 hours. All measurements returned to preoperative values at 7 days. Results of this study indicate RHCP has no long-term adverse effect on the vasculature of the extremity, as monitored by the noninvasive blood flow studies.