Sonographic guidance when using the right internal jugular vein for central vein access

From January 1986 to March 1993, 29 patients aged between 40 and 60 years with primary high grade osteosarcoma of the extremity were treated at Rizzoli Institute with neoadjuvant chemotherapy. Before surgery patients received cisplatin and adriamycin. Postoperatively, patients with a good histologic response received the same two drugs preoperatively used, while in case of poor response ifosfamide and etoposide were added to cisplatin and adriamycin. Twenty-five patients (86%) were surgically treated with a limb salvage, whereas 4 patients (14%) were amputated. With a median follow-up of 8 years (5-12), the 8-year event-free survival was 57% and the 8-year overall survival was 62%. No chemotherapy-related deaths were recorded and toxicity was manageable. These results are significantly better than those achieved in 24 patients of the same age, treated at Rizzoli Institute between 1975 and 1985 only with surgery (87% of amputation and 17% of 8-year event-free and overall survival) and indicate an advantage for the use of neo-adjuvant chemotherapy also in patients with high grade osteosarcoma of the extremity older than 40 years.     

Long-term nephrotoxicity of cisplatin, ifosfamide, and methotrexate in osteosarcoma

The acute renal effects of chemotherapy are known, but long-term nephrotoxicity has rarely been investigated. The aim of the present study was to assess long-term renal function in children and adolescents who received at-risk chemotherapy, including cisplatin, ifosfamide, and methotrexate, to treat an osteosarcoma. Renal function tests [creatinine clearance, microalbuminuria, and renal excretion of sodium, potassium, chloride, calcium, magnesium (Mg), phosphorus (P), and uric acid] were prospectively performed 5.4+/-2.2 (+/-SD) years after chemotherapy (total cumulative dose: methotrexate 41+/-31 g/m2, ifosfamide 39+/-14 g/m2, cisplatin 674+/-188 mg/m2) in 18 children and adolescents. The results were compared with 13 normal volunteers matched for age and sex. Creatinine clearance, which was greater than 80 ml/min per 1.73 m2 in all patients, correlated with the total dose of ifosfamide (r=0.55, P<0.05) and cisplatin (r=0.48, P<0.05). Microalbuminuria was noted in 4 patients. Hypomagnesemia was present in 4 and hypercalciuria in 3 patients; renal excretion of P, Mg, and uric acid was higher in patients than in controls. Glomerular function was not significantly altered and only mild tubular dysfunction was present. Since renal excretion of P and Mg were increased in patients compared with normal volunteers and hypercalciuria was occasionally seen, divalent ion disorders are the most-likely potential complications.     

Randomized trial of dose-intensity with single-agent carboplatin in patients with epithelial ovarian cancer. London Gynaecological Oncology Group

PURPOSE: We have examined the role of an increase in cisplatin dose-intensity in patients with advanced epithelial ovarian cancer by means of single-agent carboplatin therapy. PATIENTS AND METHODS: Two hundred twenty-seven patients were randomized to treatment and eligible for analysis. The dose of carboplatin was calculated according to the Calvert formula. One hundred seventeen patients received carboplatin at an area under the concentration time curve (AUC) of 6 for six courses, administered every 28 days, and 110 patients received carboplatin at an AUC of 12 for four courses, administered every 28 days. Patients were eligible provided they had not received prior chemotherapy or radiotherapy and had International Federation of Gynecology and Obstetrics stages II to IV or relapsed stage I epithelial ovarian cancer. RESULTS: The planned total-dose increase was 33% for the patients treated with carboplatin AUC 12, but the received percentage total-dose increase was 20%. There were no differences in progression-free or overall survival between the two treatment arms; the overall survival rate at 5 years was 31% and 34% of patients treated at AUCs 6 and 12, respectively. There was significantly more toxicity associated with carboplatin AUC 12, which resulted in more treatment delays and/or dose reductions (52% v 18%; P < .001). CONCLUSION: We have shown that carboplatin can be delivered at an AUC of 12 for four courses without granulocyte colony-stimulating factor support, although significant hematologic toxicity occurs. Nonhematologic toxicities were not clinically significant. Carboplatin offers an opportunity to intensify cisplatin therapy, but a greater than two-fold increase in dose-intensity probably needs to be achieved before significant effects on survival will be produced and hematologic support will be required.     

Randomized comparison of cisplatin and etoposide and either bleomycin or ifosfamide in treatment of advanced disseminated germ cell tumors: an Eastern Cooperative Oncology Group, Southwest Oncology Group, and Cancer and Leukemia Group B Study

PURPOSE: To compare standard therapy with bleomycin, etoposide, and cisplatin (BEP) to experimental therapy with etoposide, ifosfamide, and cisplatin (VIP) as primary treatment of men with advanced, disseminated germ cell tumors. PATIENTS AND METHODS: A total of 304 men with advanced disseminated germ cell tumors were randomly allocated to receive four courses of BEP or VIP. Two hundred ninety-nine patients were assessable for toxicity and 286 were assessable for response. Complete response rates, favorable response (complete remission, surgical free of disease, continuous partial remission for 2+ years), time to treatment failure, and overall survival were assessed. RESULTS: Overall complete remission rate (VIP, 37%; BEP, 31%), favorable response rate (VIP, 63%; BEP, 60%), failure-free at 2 years (VIP, 64%; BEP, 60%), and 2-year overall survival (VIP, 74%; BEP, 71%) were not significantly different between the two treatments. Grade 3 or worse toxicity, particularly hematologic and genitourinary toxicity, was significantly more common in patients who received VIP. CONCLUSION: BEP and VIP produce comparable favorable response rate and survival in patients with poor-risk germ cell tumors. The substitution of ifosfamide for bleomycin, however, was associated with significantly greater toxicity. Four courses of BEP remain the standard treatment for advanced disseminated germ cell tumors.     

Penicillin as a supplement in resolving the localized acute apical abscess

PROBLEM: Antibiotics are often prescribed indiscriminately to treat endodontic emergencies. OBJECTIVES: This study examined (1) the effect of penicillin supplementation on reduction of symptoms and (2) the course of recovery of localized acute apical abscess after emergency treatment. STUDY DESIGN: Patients with pulp necrosis and periapical pain and/or localized swelling were considered. Those eligible did not have any signs of spreading infections. Patients received appropriate local treatment, and a double-blind protocol was used to randomly assign them to one of three groups: penicillin VK group, placebo group, or neither medication group. All received ibuprofen 600 mg four times daily for 24 hours. Patients entered their pre- and postoperative pain and swelling experience on a visual analog scale for up to 72 hours. RESULTS: Resolution was fairly rapid in most patients. Statistical analysis of the scores of 32 respondents revealed no significant differences (at p < 0.05) between the three groups in course of recovery or symptoms at any time period. CONCLUSIONS: Patients with localized periapical pain or swelling generally recovered quickly with local treatment. The data did not show a demonstrable benefit from penicillin supplementation.     

Hemodynamic response to oxygen administration in chronic heart failure: role of chemoreflexes

OBJECTIVE: To determine the applicability and safety of an ifosfamide, cisplatin, and etoposide (VIP) regimen as a neoadjuvant chemotherapy to a concomitant thoracic radiotherapy and cisplatin continuous infusion in locally advanced non-small cell lung cancer (NSCLC). PATIENTS AND METHODS: Forty-four patients (stage IIIb in 43 and stage IIIa in 1) entered a study of VIP, followed by concomitant thoracic radiotherapy and cisplatin continuous infusion. Chemotherapy consisted of three courses of cisplatin 25 mg/m2, ifosfamide 1.5 g/m2 (with uroprotection), and etoposide 100 mg/m2 given on days 1 to 4 of a 21-day cycle with hematopoietic support using recombinant human methionyl granulocyte colony stimulating factor. Patients who achieved a response or a stabilization were planned to receive a split-course normofractionated thoracic radiotherapy (first course: 30 Gy/10; 4-week rest period; second course: 25 Gy/10). A continuous cisplatin infusion of 6 mg/m2 daily was administered using an autonomous chemotherapy delivery device. Total plasma platinum titration was performed daily during the two courses in five of the patients. Analyses were done on an intent-to-treat basis. RESULTS: Thirty-nine of the 44 patients received the three-cycle chemotherapy program. Received dose intensity was 82%. Thirty-eight patients received the radiotherapy and, among them, 35 received the complete concomitant continuous cisplatin infusion. Objective (complete) response rates were 48% (7%) at the end of chemotherapy and increased up to 61% (16%) by the end of radiotherapy. At the end of the first radiotherapy cycle, the mean total plasma platinum concentration was twice as high as that of the residual postinduction chemotherapy concentration. During induction chemotherapy, myelosuppression was the limiting toxicity requiring hospital readmission in 23 patients. During radiotherapy, the main toxicity was acute esophagitis. A relatively high rate of pulmonary fibrosis was observed using the subjective objective management analytic--late effects of normal tissue score without life-threatening pulmonary function impairment. None of the patients died from toxic reactions. Probability of survival at 1, 2, and 3 years was 49%, 19%, and 5%, respectively. Primary cause of failure was a local relapse in 63% of the patients, brain metastases in 24%, and hematogeneous metastases to other sites in 13%. CONCLUSION: Neoadjuvant VIP followed by concomitant radiotherapy-chemotherapy is feasible, but the split-course radiotherapy did not prevent a high rate of local recurrences. The high rate of toxic reactions requiring hospital readmission limits further development of such an aggressive regimen in NSCLC.     

High-dose chemotherapy with autologous hematopoietic progenitor-cell support as part of combined modality therapy in patients with inflammatory breast cancer

PURPOSE: To evaluate the feasibility of high-dose chemotherapy (HDC) with autologous hematopoietic progenitor-cell support (AHPCS) as part of combined modality therapy (CMT) in patients with inflammatory breast cancer (IBC). PATIENTS AND METHODS: From April 1993 to March 1997, 30 patients with IBC were treated at our program. Twenty-three patients received neoadjuvant chemotherapy (NAC) before HDC; 18 patients also received adjuvant chemotherapy following surgery, but before HDC. All patients received HDC with high-dose cyclophosphamide, cisplatin, and carmustine (BCNU) with AHPCS. Every patient underwent surgery either before (27 patients) or after (three patients) HDC. Patients received radiotherapy after HDC in addition to tamoxifen if their tumors were estrogen receptor-positive. RESULTS: Thirteen patients experienced grade 3 or 4 nonhematologic noninfectious toxicities. In 12 patients (40%), this represented drug-induced lung injury, which in all cases responded to a 10-week course of corticosteroids. The only treatment-related death was secondary to hemolytic-uremic syndrome (HUS). Another patient suffered grade 4 CNS toxicity, which was completely reversible. All patients engrafted promptly. Eight patients relapsed, five of whom had a poor pathologic response to NAC. Relapses were local (five patients), local plus systemic (one), or systemic only (two). Median follow-up time from diagnosis and HDC is 23.5 (range, 7 to 49) and 19 (range, 4 to 44) months, respectively. Twenty-one patients (70%; 95% confidence interval [CI], 51% to 86%) remain alive and free of disease 4 to 44 months after HDC. Median disease-free survival (DFS) and overall survival have not yet been reached. CONCLUSION: HDC as part of CMT is feasible in patients with IBC. The toxicity of this treatment program is significant, but tolerable. Despite the short follow-up duration, the promising DFS observed in this group of patients warrants randomized studies that include a HDC-containing arm in patients with IBC.     

Musical auditory hallucinosis from Listeria rhombencephalitis

We present the unusual case of a 27-year-old Japanese woman who exhibited recurrences of metastatic tumors from uterine leiomyosarcoma after five operations. Chemotherapy with cisplatin, pirarubicin, and cyclophosphamide was ineffective. Substituting ifosfamide for cyclophosphamide, we obtained a complete response. The Gynecologic Oncology Group (GOG) in the United States has recognized the efficacy of ifosfamide and mesna in the treatment of patients with advanced or recurrent uterine sarcomas. Here we report on the efficacy of ifosfamide in addition to cisplatin and pirarubicin.     

Prevention of CNS disease in intermediate-risk acute lymphoblastic leukemia: comparison of cranial radiation and intrathecal methotrexate and the importance of systemic therapy: a Childrens Cancer Group report

PURPOSE: This study (Childrens Cancer Group [CCG]-105) was designed in part to determine in a prospective randomized trial whether intrathecal methotrexate (IT MTX) administered during induction, consolidation, and maintenance could provide protection from CNS relapse equivalent to that provided by cranial radiation (CXRT) in children with acute lymphoblastic leukemia (ALL) and intermediate-risk features. PATIENTS AND METHODS: We randomized 1,388 children with intermediate-risk ALL to the two CNS regimens. They received either IT MTX at intervals throughout their course of therapy or CXRT (18 Gy) during consolidation with IT MTX during induction, consolidation, and delayed intensification. Systemic therapy was randomized to one of four treatment regimens derived from a regimen used by CCG in recent studies for this patient population and three more intensive regimens based on the Berlin-Frankfurt-Munster trials. RESULTS: Life-table estimates at 7 years show a 93% and 91% CNS relapse-free survival rate for the CXRT and IT MTX groups, respectively. The corresponding event-free survival (EFS) rates are 68% and 64%. The differences are not significant. Patients who received more intensive systemic therapy had a 94% CNS relapse-free survival rate on either CXRT or IT MTX, while patients who received standard systemic therapy had 90% and 80% rates for CXRT and IT MTX, respectively (P < .0001). Patients less than 10 years of age who received CXRT or IT MTX had 72% and 71% EFS rates if they received more intensive systemic therapy. Patients 10 years or older who received CXRT had an improved EFS (61% v 53%) with a more intensive systemic program. This was primarily due to fewer bone marrow relapses (P = .04). CONCLUSIONS: IT MTX during induction, consolidation, and maintenance provides protection from CNS relapse in patients with intermediate-risk ALL equivalent to that provided by CXRT if more intensive systemic therapy is given. The CNS relapse rate with either CXRT or IT MTX is in part dependent on the associated systemic therapy. For intermediate-risk patients less than 10 years of age, IT MTX with an intensified systemic regimen provided CNS prophylaxis comparable to that provided by CXRT, whereas older patients had fewer systemic relapses if they received CXRT.     

Oral ondansetron for the control of cisplatin-induced delayed emesis: a large, multicenter, double-blind, randomized comparative trial of ondansetron versus placebo

PURPOSE: To investigate the efficacy and safety of oral ondansetron in the control of cisplatin-induced delayed emesis in patients who do not require rescue antiemetic therapy for acute emesis. PATIENTS AND METHODS: Five hundred thirty-eight chemotherapy-naive patients who received cisplatin chemotherapy (> or = 70 mg/m2), and who were not rescued for acute emesis, were eligible to be randomized to receive one of the three oral regimens to control delayed emesis. Group I received placebo on days 2 to 6; group II received ondansetron 8 mg twice daily on days 2 and 3 and placebo on days 4 to 6; group III received ondansetron 8 mg twice daily on days 2 to 6. All patients received intravenous ondansetron (0.15 mg/kg every 4 hours for three doses) for the control of acute emesis on day 1. The number of emetic episodes on days 2 and 3 combined (days 2/3, when incidence and severity of delayed emesis were expected to be greatest) was considered the primary measure of efficacy. RESULTS: Patients who received odansetron had significantly fewer emetic episodes on days 2/3, 4, and 5 than those who received placebo (P < or = .002 on each day). Additionally, significantly more patients who received ondansetron had a complete plus major response (C+MR; < or = two two emetic episodes) than those who received placebo on days 2/3 (56% v 37%, P = .001), 4 (94% v 85%, P = .005), and 5 (98% v 88%, P = .006). Patients who received ondansetron had significantly less nausea on day 2/3 when day-1 nausea was used as the baseline score (P = .025). Patients who received ondansetron also had significantly less nausea on day 4 (P = .042) and the results approached significance on day 5 (P = .066). CONCLUSION: Oral ondansetron had a significant effect in the control of cisplatin-induced delayed emesis and nausea in patients who had not required rescue antiemetics during the acute emesis period. The control of delayed nausea and vomiting was most notable in the immediate 2 days following cisplatin administration, with the clinical difference narrowing between the two treatment arms on subsequent days.     

Factors determining the weaning outcome

OBJECTIVE: To identify the clinicopathological and chemoresistant factors predicting the response to neoadjuvant chemotherapy and the patient prognosis in high-risk cervical carcinomas. METHODS: We retrospectively reviewed 47 patients with locally advanced or bulky cervical carcinoma treated with two courses of intraarterial infusion of cisplatin, doxorubicin, mitomycin C, and 5-fluorouracil (5-FU), followed by radical hysterectomy at our hospital between 1988 and 1995. Expressions of the chemoresistance-related proteins, such as P-glycoprotein, glutathione S-transferase pi (GST-pi), and proliferating cell nuclear antigen (PCNA) in the tumor cells, were examined by immunohistochemistry using pretreatment biopsy specimens. These results were compared with the chemotherapeutic response, which was evaluated by magnetic resonance imaging (MRI) and histopathology. Outcome of the patients was also studied. RESULTS: Chemotherapeutic effect of either complete (CR) or partial (PR) response on MRI was obtained in 36 of the 47 (86%) patients. Poor response to chemotherapy was significantly correlated with P-glycoprotein expression (P < 0.005) and low PCNA labeling (P < 0. 05), but not GST-pi expression in the tumor cells. Independent prognostic factors for patient survival were parametrial involvement and lymph node metastasis. Neither the expression of GST-pi nor PCNA was correlated with the patient survival. CONCLUSION: Assessment of the expression of P-glycoprotein and PCNA is potentially useful for the prediction of tumor response to neoadjuvant chemotherapy for cervical carcinomas.     

Evaluation of intra-arterial infusion chemotherapy for advanced gastric cancer

We evaluated the therapeutic efficacy of intraarterial infusion chemotherapy in advanced gastric cancer, its side effect and patient prognosis, in comparison with systemic infusion. Of 125 cases of advanced gastric cancer, 41 cases received intraarterial chemotherapy (A group) and the rest were given systemic infusion (S group). Protocols of chemotherapy were 5-FU + MTX in 49 cases, 5-FU + cisplatin in 62, and 5-FU + MMC in 14. Location of the disease was the peritoneum in 69 cases, nodes in 59, liver in 38, and other sites, 33. The response rate of A group was significantly higher than that of S group, at 31% and 13% respectively. Although 41% of cases showed side effects (> or = grade 2), there was no significant difference between the 2 groups. The median survival period and 1-year survival rate were 8.4 months and 35%, respectively, and there was no significant difference between the 2 groups. In cases with liver metastasis, the prognosis of A group was better than that of S group. The results suggest that intra-arterial infusion chemotherapy is an effective treatment for liver metastasis from gastric cancer.     

Chemotherapy followed by surgery compared with surgery alone for localized esophageal cancer

BACKGROUND: We performed a multi-institutional randomized trial comparing preoperative chemotherapy followed by surgery with surgery alone for patients with local and operable esophageal cancer. METHODS: Preoperative chemotherapy for patients randomly assigned to the chemotherapy group included three cycles of cisplatin and fluorouracil. Surgery was performed two to four weeks after the completion of the third cycle; patients also received two additional cycles of chemotherapy after the operation. Patients randomly assigned to the immediate-surgery group underwent the same surgical procedure. The main end point was overall survival. RESULTS: Of the 440 eligible patients with adequate data , 213 were assigned to receive preoperative chemotherapy and 227 to undergo immediate surgery. After a median possible study time of 55.4 months, there were no significant differences between the two groups in median survival: 14.9 months for the patients who received preoperative chemotherapy and 16.1 months for those who underwent immediate surgery (P=0.53). At one year, the survival rate was 59 percent for those who received chemotherapy and 60 percent for those who had surgery alone; at two years, survival was 35 percent and 37 percent, respectively. The toxic effects of chemotherapy were tolerable, and the addition of chemotherapy did not appear to increase the morbidity or mortality associated with surgery. There were no differences in survival between patients with squamous-cell carcinoma and those with adenocarcinoma. Weight loss was a significant predictor of poor outcome (P=0.03). With the addition of chemotherapy, there was no change in the rate of recurrence at locoregional or distant sites. CONCLUSIONS: Preoperative chemotherapy with a combination of cisplatin and fluorouracil did not improve overall survival among patients with epidermoid cancer or adenocarcinoma of the esophagus.     

Allergen-specific increase in interleukin (IL)-4 and IL-5 secretion from peripheral blood mononuclear cells during birch-pollen immunotherapy

BACKGROUND: In the multicenter European Intergroup Cooperative Ewing's Sarcoma Studies, localized Ewing tumors of bone were treated by combination chemotherapy with surgery and/or radiotherapy. Patients with primary metastases (pm-pts) were treated in high risk protocols. PATIENTS AND METHODS: One hundred seventy-seven pm-pts were registered from January 1990 to December 1995, 171 were evaluable for survival analyses. Thirty-six pm-pts received myeloablative megatherapy with stem cell rescue following conventional treatment. Bilateral whole lung irradiation (WLI) was administered in 57 pm-pts with pulmonary involvement. Event-free survival (EFS) rates were estimated by Kaplan-Meier analysis. Prognostic factors were identified by log-rank statistics, Cox procedures and logistic regression. RESULTS: Eighty-nine deaths were recorded by 1 February 1997, EFS four years after diagnosis for all 171 pm-pts was 0.27. EFS for isolated lung metastases was 0.34, for bone/bone marrow (BM) metastases, 0.28, and for combined lung plus bone/BM metastases, 0.14 (P < 0.005). WLI improved outcome in case of isolated pulmonary involvement (0.40 vs. 0.19, P < 0.05). In pm-pts with combined pulmonary/skeletal metastases, intensification by megatherapy and/or WLI improved EFS from 0.00 to 0.27 (P = 0.0001). CONCLUSIONS: EFS four years after diagnosis in patients with disseminated Ewing tumors is 0.27. Whole lung irradiation and megatherapy improve outcome in subgroups of patients with disseminated Ewing tumors is 0.27. Whole lung irradiation and megatherapy improve outcome in subgroups of patients with disseminated Ewing disease.     

Prognostic implications of downstaging following preoperative radiation therapy for operable T3-T4 rectal cancer

PURPOSE: Squamous cancer of the upper aerodigestive tract is a disheartening disease. Despite our best efforts, the long-term survival rate remains only 15% to 40%, and surgical cures often decrease the quality of life owing to the loss of swallowing and speech organs. A better understanding of tumor dynamics and the discovery that thiosulfate can neutralize cisplatin led us to develop a treatment plan that combines a rapid superselective high-dose intraarterial delivery of cisplatin (CDDP), simultaneous intravenous infusion of its antagonist, thiosulfate, and radiation therapy. METHODS: Patients with advanced head and neck squamous cancer were entered into the protocol after a multidisciplinary evaluation that included CT or MR imaging. Forty-two patients constituted the first cohort. After baseline angiography, an arterial acceptance test determined the maximum infusion rate that the tumor's nutrient artery would accept. CDDP was then infused at that rate, usually within 3 to 5 minutes, while the antagonist thiosulfate was given intravenously. In the second cohort of 85 patients with stage 3 or 4 previously untreated and unresectable disease, local radiation was added to the treatment plan. The radiation dose (180-200 cGy/d x 35) was delivered regionally on the basis of the known radiosensitizing effect of CDDP. RESULTS: Cohort 1 allowed us to develop the infusion technique and to establish a dose quantity and delivery frequency. When 150 mg/m2 was administered weekly for 4 weeks, no severe toxicity was found. In cohort 2, 72 (92%) of the remaining 78 patients had complete disappearance of their tumor. Seventeen severe toxic events were associated with 323 femoral catheterizations. One patient died of pulmonary embolus, precluding follow-up evaluation. Six patients had neurologic sequelae, three with transient and three with permanent strokes. CONCLUSION: Rapid superselective chemotherapy with CDDP combined with a circulatory systemic antagonist allowed delivery of an antitumoral drug directly into the lesion while protecting the kidneys and bone marrow from the agent's systemic effects. Use of a dose regimen of 150 mg CDDP/m2 per week for 4 weeks resulted in the disappearance of a large percentage of advanced squamous cancers.     

Phase II trial of intraperitoneal paclitaxel in carcinoma of the ovary, tube, and peritoneum: a Gynecologic Oncology Group Study

PURPOSE: To determine the response rate of intraperitoneal (i.p.) paclitaxel in patients with small-volume residual carcinomas of the ovary, fallopian tube, or peritoneum. PATIENTS AND METHODS: Eligibility criteria included patients with one of the cancers noted above, with the largest residual disease 0.5 cm or less in maximum diameter at the end of second-look surgery, and prior treatment with systemic paclitaxel was permitted. The treatment plan was paclitaxel 60 mg/m2 i.p. weekly for 16 weeks, followed by surgical evaluation in patients without evidence of disease progression. RESULTS: Of 80 patients entered onto the study, 76 were eligible, of whom 86% were considered to be potentially cisplatin-sensitive. Although five patients (7%) did not complete the first course of therapy because of catheter leakage or blockade, 53 patients (70%) received all 16 planned courses. Only 14 patients (18%) received fewer than 11 courses. Treatment was well tolerated, which included only moderate abdominal pain (grade 2, 12 patients; grade 3, one patient) and minimal neutropenia (grade 2, three patients; grade 3, one patient). Of 28 assessable patients with microscopic disease at the start of i.p. therapy, 17 patients (61%) achieved a surgically defined complete response (CR). Only one of 31 patients (3%) with any macroscopic disease achieved a CR. Of the eligible patients, 18 of 76 (24%) achieved a CR. CONCLUSION: Salvage i.p. paclitaxel is tolerable and active in patients with microscopic residual disease. The impact of this treatment strategy on survival remains to be assessed in a phase III trial.     

Sequential intrahepatic fluorodeoxyuridine and systemic fluorouracil plus leucovorin for the treatment of metastatic colorectal cancer confined to the liver

PURPOSE: Extrahepatic metastasis represents a frequent pattern of disease progression when fluorodeoxyuridine (FUDR) is given by the intraarterial route for the treatment of unresectable colorectal liver metastases. Systemic fluorouracil (5-FU) plus leucovorin was added to intrahepatic FUDR to prolong the duration of disease control. METHODS: Only patients with colorectal cancer who had evidence of unresectable metastases confined to the liver were eligible. Laparotomy was performed to establish arterial perfusion of the liver. Cycles of intrahepatic FUDR followed by a 1-week rest period then intravenous chemotherapy with 5-FU plus leucovorin were administered until maximal regression of hepatic metastases. Maintenance chemotherapy with 5-FU plus leucovorin was then given until disease progression. RESULTS: Fifty-seven patients entered this trial; four patients (7%) were ineligible and 13 (23%) did not receive any chemotherapy on study because of findings at laparotomy. The 40 eligible patients who began chemotherapy are included in the statistical analyses. Twenty-five patients (62% of those who received chemotherapy) experienced regression of liver metastases. The median time to tumor progression was 9 months, but only 3% remained progression-free at 24 months. The median survival duration was 18 months. Toxicity was tolerable with no cases of biliary sclerosis. One treatment-related fatality due to sepsis was observed. CONCLUSION: Although short-term treatment results appear to be somewhat better than we have previously observed with intrahepatic FUDR alone, the sequential regimen did not have an impact on long-term, progression-free survival in patients with unresectable liver metastases. We are now investigating this regimen as surgical adjuvant therapy in selected patients following hepatic metastasectomy where this aggressive approach might have a greater therapeutic effect in the minimal residual disease setting.     

Hyperfractionated irradiation with or without concurrent chemotherapy for locally advanced head and neck cancer

BACKGROUND: Radiotherapy is often the primary treatment for advanced head and neck cancer, but the rates of locoregional recurrence are high and survival is poor. We investigated whether hyperfractionated irradiation plus concurrent chemotherapy (combined treatment) is superior to hyperfractionated irradiation alone. METHODS: Patients with advanced head and neck cancer who were treated only with hyperfractionated irradiation received 125 cGy twice daily, for a total of 7500 cGy. Patients in the combined-treatment group received 125 cGy twice daily, for a total of 7000 cGy, and five days of treatment with 12 mg of cisplatin per square meter of body-surface area per day and 600 mg of fluorouracil per square meter per day during weeks 1 and 6 of irradiation. Two cycles of cisplatin and fluorouracil were given to most patients after the completion of radiotherapy. RESULTS: Of 122 patients who underwent randomization, 116 were included in the analysis. Most patients in both treatment groups had unresectable disease. The median follow-up was 41 months (range, 19 to 86). At three years the rate of overall survival was 55 percent in the combined-therapy group and 34 percent in the hyperfractionation group (P=0.07). The relapse-free survival rate was higher in the combined-treatment group (61 percent vs. 41 percent, P=0.08). The rate of locoregional control of disease at three years was 70 percent in the combined-treatment group and 44 percent in the hyperfractionation group (P=0.01). Confluent mucositis developed in 77 percent and 75 percent of the two groups, respectively. Severe complications occurred in three patients in the hyperfractionation group and five patients in the combined-treatment group. CONCLUSIONS: Combined treatment for advanced head and neck cancer is more efficacious and not more toxic than hyperfractionated irradiation alone.     

Chemotherapy for advanced sarcoma: therapeutic decisions and modalities

In patients who have advanced soft tissue sarcoma that is no longer localized, systemic chemotherapy is the most reasonable option for treatment. The decision to treat or to use experimental or conventional agents should be based on the clinical assessment of anticipated net benefit in quality of life as well as the remote possibility of complete remission or even cure. Asymptomatic elderly patients with relatively stable disease might best be treated with watchful waiting; whereas younger excellent-performance-status patients should be offered the opportunity of participating in phase II or phase I studies of newer drugs and intensification regimens. Of the currently available single agents, only doxorubicin (or epirubicin) and ifosfamide show response rates greater than 20%; both show a definite dose-response relationship. Dacarbazine shows particular activity in uterine leiomyosarcomas. Combination chemotherapy regimens such as doxorubicin-ifosfamide show a higher response rate, but may be more toxic. New agents are needed. The current progress in our understanding of the molecular biology of sarcomas, and our expanded comprehension of the mechanism of action of cytotoxic drugs and the biology of drug resistance is cause for optimism.     

Multidisciplinary management of hepatocellular carcinoma

BACKGROUND/AIMS: The continuing poor prognosis for patients with hepatocellular carcinoma drives a search for new adjuvant therapies. Targeted locoregional immuno-chemotherapy is one of the most promising. MATERIALS AND METHODS: From 1990 to 1996, 193 patients who were not eligible for liver resection were treated in a prospective randomized study. Ninety-one patients received locoregional targeted chemotherapy only via an arterial catheter (Group A), and 102 received combined locoregional immuno-chemotherapy via two arterial catheters (Group B). RESULTS: Overall survival was significantly different (10.2 months vs 22.3 months), favoring Group B. Complications and side effects of treatment were minimal in Group B and easily handled. Even in Group A, side effects were less severe than effects normally associated with systemic chemotherapy. CONCLUSIONS: Even though the current prognosis for patients with Hepatocellular Carcinoma remains poor, targeted locoregional immuno-chemotherapy has proven to be of benefit in terms of quality of life and survival.