ABSTRACT
Background: Use of chemotherapy near the end of life in patients with metastatic cancer is often ineffective and toxic. Data about the factors associated with its use remain scarce, especially in Europe. Methods: Nationwide, register-based study including all hospitalized patients aged ≥20 years who died from metastatic solid tumors in France between 2010 and 2013. Results: A total of 279 846 hospitalized patients who died from metastatic cancer were included. During the last month before death, 19.5% received chemotherapy (including 11.3% during the last 2 weeks). Female sex (OR= 0.96, 95% CI= 0.93-0.98), older age (OR= 0.70, 95% CI= 0.69-0.71 for each 10-year increase) and higher number of chronic comorbidities (OR= 0.83, 95% CI= 0.82-0.84) were independently associated with lower rates of chemotherapy. Although patients with chemosensitive tumors were statistically more likely to receive chemotherapy during the last month before death (OR= 1.21, 1.18-1.25), this association was mostly fueled by testis and ovary tumors and we found no obvious pattern between the expected chemosensitivity of different cancers and the rates of chemotherapy use close to death. Compared with university hospitals, patients who died in for-profit clinics/hospital (OR= 1.40, 95% CI= 1.34-1.45), or comprehensive cancer centers (OR= 1.43, 95% CI= 1.36-1.50) were more likely to receive chemotherapy. Finally, high-volume centers and hospitals without palliative care units reported greater-than-average rates of chemotherapy near the end of life. Conclusion: among hospitalized patients with cancer, young individuals, treated in comprehensive cancer centers or in high-volume centers without palliative care units were the most likely to receive chemotherapy near the end of life. We found no evident pattern between the expected chemosensitivity of different cancers and the probability for patients to receive chemotherapy close to death.
Subject(s)
Antineoplastic Agents/therapeutic use , Neoplasms/drug therapy , Terminal Care/statistics & numerical data , Adult , Aged , Aged, 80 and over , Female , Humans , Male , Middle Aged , Retrospective StudiesABSTRACT
BACKGROUND: Sorafenib is an oral anticancer agent targeting Ras-dependent signaling and angiogenic pathways. A phase I trial demonstrated that the combination of gemcitabine and sorafenib was well tolerated and had activity in advanced pancreatic cancer (APC) patients. The BAYPAN study was a multicentric, placebo-controlled, double-blind, randomized phase III trial comparing gemcitabine/sorafenib and gemcitabine/placebo in the treatment of APC. PATIENTS AND METHODS: The patient eligibility criteria were locally advanced or metastatic pancreatic adenocarcinoma, no prior therapy for advanced disease and a performance status of zero to two. The primary end point was progression-free survival (PFS). The patients received gemcitabine 1000 mg/m(2) i.v., weekly seven times followed by 1 rest week, then weekly three times every 4 weeks plus sorafenib 200 mg or placebo, two tablets p.o., twice daily continuously. RESULTS: Between December 2006 and September 2009, 104 patients were enrolled on the study (52 pts in each arm) and 102 patients were treated. The median and the 6-month PFS were 5.7 months and 48% for gemcitabine/placebo and 3.8 months and 33% for gemcitabine/sorafenib (P = 0.902, stratified log-rank test), respectively. The median overall survivals were 9.2 and 8 months, respectively (P = 0.231, log-rank test). The overall response rates were similar (19 and 23%, respectively). CONCLUSION: The addition of sorafenib to gemcitabine does not improve PFS in APC patients.
Subject(s)
Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Deoxycytidine/analogs & derivatives , Niacinamide/analogs & derivatives , Pancreatic Neoplasms/drug therapy , Phenylurea Compounds/therapeutic use , Adult , Aged , Aged, 80 and over , Antimetabolites, Antineoplastic/administration & dosage , Antimetabolites, Antineoplastic/adverse effects , Antimetabolites, Antineoplastic/therapeutic use , Antineoplastic Agents/administration & dosage , Antineoplastic Agents/adverse effects , Antineoplastic Agents/therapeutic use , Antineoplastic Combined Chemotherapy Protocols/adverse effects , Deoxycytidine/administration & dosage , Deoxycytidine/adverse effects , Deoxycytidine/therapeutic use , Disease-Free Survival , Double-Blind Method , Female , Humans , Male , Middle Aged , Niacinamide/administration & dosage , Niacinamide/adverse effects , Niacinamide/therapeutic use , Phenylurea Compounds/administration & dosage , Phenylurea Compounds/adverse effects , Placebos , Protein Kinase Inhibitors/administration & dosage , Protein Kinase Inhibitors/adverse effects , Protein Kinase Inhibitors/therapeutic use , Ribonucleotide Reductases/antagonists & inhibitors , Sorafenib , GemcitabineABSTRACT
Hepatocellular carcinoma is now a major public health concern. In intermediate stages (one third of hepatocellular carcinoma patients), chemoembolization is the standard of care despite a poor tolerance and a moderate efficacy. Moreover, despite recent improvements, this technique seems in a dead end. Radioembolization could be an excellent tool for such patients. Currently (131)I-Lipiodol, (188)Re-Lipiodol, (90)Y-glass or resin microspheres are available. More recent and promising data come from microspheres, but phase II and III studies are needed before drawing any conclusion. In the future, the combination of radioembolization with systemic chemotherapy or targeted agents (particularly antiangiogenic drugs) seems very promising.
Subject(s)
Carcinoma, Hepatocellular/therapy , Embolization, Therapeutic/methods , Liver Neoplasms/therapy , Microspheres , Antineoplastic Agents/administration & dosage , Ethiodized Oil/administration & dosage , Humans , Radioisotopes/administration & dosage , Rhenium/administration & dosage , Yttrium Radioisotopes/administration & dosageABSTRACT
To assess feasibility and tolerance of a modification in the usual radiochemotherapy regimen for esophageal cancer by using a leucovorin, 5-fluorouracil bolus, and infusion-cisplatin regimen (six cycles), beginning with two cycles of chemotherapy before conventional radiotherapy (50 Gy), 33 patients, 30 were men, 62.8 +/- 9.5 years, were treated for an esophageal carcinoma (29 squamous cell), 27 of these were in stage III (based on computed tomography scan). Neoadjuvant chemotherapy was well tolerated; concomitant radiochemotherapy was associated with severe adverse events mostly hematological in 23 patients. Complete response was achieved in 70%; median overall survival was 14 months, and 2-year survival was 40 +/- 11%. More than one-third of cycles could be performed as outpatients. This regimen seems safe and efficient, and could be conducted in an outpatient basis.
Subject(s)
Antineoplastic Agents/administration & dosage , Cisplatin/administration & dosage , Esophageal Neoplasms/drug therapy , Esophageal Neoplasms/radiotherapy , Fluorouracil/administration & dosage , Leucovorin/administration & dosage , Vitamin B Complex/administration & dosage , Aged , Chemotherapy, Adjuvant , Combined Modality Therapy , Drug Administration Schedule , Female , Humans , Male , Middle Aged , Neoadjuvant Therapy , Pilot ProjectsABSTRACT
Hepatocellular carcinoma (HCC) is a major health concern worldwide. Several therapeutic options are available, but transplantation is the only curative option; for the vast majority of patients, the remaining alternative is palliative care. There is some hope however with Lipiodol which, when injected into the hepatic artery remains concentrated in the liver and specifically within the malignant tumor for a long period of time. This feature has been used for internal radiation therapy using (131)Iodine-labeled Lipiodol. Phase III studies with (131)I-Lipiodol have demonstrated, in an adjuvant setting improved recurrence-free and overall survival compared with surgery alone and in a palliative setting improved survival among patients with portal thrombosis. Comparison with chemoembolization has shown similar results in terms of efficacy but with better tolerance for (131)I-lipiodol. The method would also be useful for small nodules not amendable to surgery or percutaneous treatment. The use of another radionuclide, (188)Re, could probably improve the current method by reducing the need for radioprotection. New perspectives will be forthcoming with the advent of targeted drugs using combinations in sequential or concomitant regimens.
Subject(s)
Carcinoma, Hepatocellular/radiotherapy , Carcinoma, Hepatocellular/secondary , Iodine Radioisotopes/therapeutic use , Iodized Oil/therapeutic use , Liver Neoplasms/radiotherapy , Humans , Radiopharmaceuticals/therapeutic use , Radiotherapy DosageABSTRACT
BACKGROUND: This multicenter adjuvant phase III trial evaluated the addition of irinotecan to LV5FU2 in colon cancer patients at high risk of relapse. PATIENTS AND METHODS: A total of 400 patients with histologically proven primary colon cancer with postoperative N1 detected by occlusion/perforation or N2 were randomised to: A-LV5FU2 [leucovorin 200 mg/m(2), 2-h infusion, 5-fluorouracil (5-FU) 400 mg/m(2) bolus, 600 mg/m(2) 22-h continuous infusion, days 1 and 2] or B-LV5FU2 + IRI (irinotecan 180 mg/m(2) 90-min infusion day 1 + LV5FU2) fortnightly for 12 cycles. Primary end point was disease-free survival (DFS). RESULTS: Median follow-up was 63 months. Significantly more T4 tumours and 15 or more positive lymph nodes were observed in arm B. 5-FU relative dose intensity (RDI) was >0.80 for 94% and 77% in arms A and B, respectively (P < 0.001). Irinotecan RDI was >0.80 for 70% patients. There were more grades 3 and 4 neutropenia in arm B (4% versus 28%, P < 0.001). The 3-year DFS was 60% [95% confidence interval (CI) 53% to 66%] and 51% (95% CI 44% to 58) in arms A and B, respectively. No difference was observed [hazard ratio (HR) = 1.12, 95% CI 0.85-1.47, P = 0.42] even when adjusted for prognostic factors (adjusted HR = 0.98, 95% CI 0.74-1.31, P = 0.92). The 5-year overall survival (OS) was 67% (95% CI 59% to 73%) and 61% (95% CI 53% to 67%) in arms A and B, respectively. CONCLUSION: Adjuvant LV5FU2 + IRI compared with LV5FU2 alone in patients at high risk of relapse showed no improvement in DFS and OS.
Subject(s)
Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Colonic Neoplasms/drug therapy , Aged , Antineoplastic Combined Chemotherapy Protocols/adverse effects , Camptothecin/administration & dosage , Camptothecin/analogs & derivatives , Disease-Free Survival , Female , Fluorouracil/administration & dosage , Humans , Irinotecan , Leucovorin/administration & dosage , Male , Middle Aged , Recurrence , Risk AssessmentABSTRACT
LV5FU2 with high-dose leucovorin (LV), weekly infusional 5-fluorouracil (5FU) (AIO schedule) and raltitrexed have been demonstrated to be active agents in first-line treatment of colorectal cancer. We performed a 4-arm randomised trial to compare (1) a low-dose intravenous bolus of LV (20 mg/m2), followed by an intravenous bolus of 5FU (400 mg/m2), followed by a 22-hour continuous infusion of 5FU (600 mg/m2) on day 1 and day 2/2 weeks (ldLV5FU2 arm), (2) a weekly continuous infusion of high-dose 5FU (2.6 g/m2/week) for 6 weeks followed by a rest week (HD-FU arm) and (3) raltitrexed (Tomudex arm; 3 mg/m2/3 weeks) to standard LV5FU2. From 1997 to 2001, 294 patients were included. The 4 arms were well balanced for sex ratio, age, WHO performance status, the primary tumour site and prior adjuvant chemotherapy. Treatment was stopped due to low accrual. Two toxicity-related deaths were observed in the Tomudex arm. The treatments gave rise to different rates of grade 3-4 neutropenia (3, 4, 11 and 14% of the patients in the LV5FU2, ldLV5FU2, HD-FU and Tomudex arms, respectively, p = 0.028), leucopenia and vomiting. At least one episode of grade 3-4 toxicity was observed in 27, 25, 38 and 47% of the patients in the LV5FU2, ldLV5FU2, HD-FU and Tomudex arms, respectively (p = 0.016). An objective response was observed in 28, 21, 22 and 10% of the patients in the LV5FU2, ldLV5FU2, HD-FU and Tomudex arms, respectively (p = 0.04). Progression-free survival (PFS) of the patients in the Tomudex arm was statistically lower compared to that of patients treated with LV5FU2 or ldLV5FU2 (combined group; p = 0.013, log rank test). In conclusion, Tomudex is more toxic and yields shorter PFS than infusional 5FU. Despite the early closure of the study and the lack of power of the comparison, it seems that ldLV5FU2 could be considered as an active, easier and less expensive option for the treatment of metastatic colorectal cancer compared to classic LV5FU2 or weekly HD-FU.
Subject(s)
Antineoplastic Combined Chemotherapy Protocols/administration & dosage , Antineoplastic Combined Chemotherapy Protocols/adverse effects , Colorectal Neoplasms/drug therapy , Colorectal Neoplasms/pathology , Aged , Antimetabolites, Antineoplastic/administration & dosage , Chemotherapy, Adjuvant , Disease-Free Survival , Drug Administration Schedule , Female , Fluorouracil/administration & dosage , Fluorouracil/adverse effects , France , Humans , Infusions, Intravenous , Male , Middle Aged , Neoplasm Staging , Quality of Life , Quinazolines/administration & dosage , Quinazolines/adverse effects , Thiophenes/administration & dosage , Thiophenes/adverse effects , Treatment OutcomeABSTRACT
BACKGROUND: Recurrence is common after surgery for hepatocellular carcinoma (HCC). METHODS: The efficacy of, and tolerance to, preoperative intra-arterial injection of (131)I-labelled lipiodol was examined in 34 patients with HCC, including 29 with cirrhosis. Twenty-five patients had a single hepatic tumour and the mean(s.d.) tumour size was 5.2(3.7) (range 2-15) cm. The patients received between one and three injections of (131)I-labelled lipiodol (60 mCi per injection) before surgery. Operations included 14 liver transplants, 13 minor hepatectomies, six major hepatectomies and one exploratory laparotomy. RESULTS: There was one complication after lipiodol injection due to acute ischaemia of the small bowel. Three of 34 patients died within 28 days, two after transplantation and one after resection. An objective tumour response (decrease in tumour size) was observed in 19 of 34 patients, and a complete histological response in eight of 34. There was an objective tumour response or major histological necrosis of lesions in 25 of 34 patients. The 5-year survival rate was 48.4(8.0) per cent, 69.0 per cent after transplantation and 36.0 per cent in patients who underwent resection. CONCLUSION: This preoperative method appeared to be well tolerated, and provided promising results in terms of macroscopic and microscopic tumour responses.
Subject(s)
Carcinoma, Hepatocellular/radiotherapy , Contrast Media , Iodine Radioisotopes/administration & dosage , Iodized Oil/administration & dosage , Liver Neoplasms/radiotherapy , Carcinoma, Hepatocellular/surgery , Female , Hepatectomy/methods , Hepatectomy/mortality , Humans , Injections, Intra-Arterial , Liver Neoplasms/surgery , Liver Transplantation/methods , Liver Transplantation/mortality , Male , Middle Aged , Neoplasm Recurrence, Local/prevention & control , Preoperative Care/methods , Survival Analysis , Treatment OutcomeABSTRACT
The intra-arterial administration of 131I-lipiodol is a therapeutic approach increasingly used for the treatment of inoperable hepatocellular carcinomas. This technique has even become the reference treatment for hepatocellular carcinomas with portal thrombosis and is the only effective treatment to reduce the risk of recurrence among patients who could benefit from surgical operation. Currently, few data have been published concerning the levels of exposure for personnel carrying out this type of treatment. We undertook a dosimetric study targeted mainly on the exposure of the person performing the injection of 131I-lipiodol to show that this treatment can be carried out with an exposure at the extremities distinctly lower than the regulatory annual threshold by using simple means of radioprotection. The point of puncture was carried out at the level of left femoral artery, the preparation and injection of the therapeutic dose was carried out extemporaneously by the nuclear medicine specialist using a 10 ml syringe (for an injected volume of 4 ml) fitted with an adapted syringe protector. The injection was carried out as rapidly as possible under scopic control while avoiding reflux, with compression carried out by the radiologist. This study comprises 52 intra-arterial injections of 131I-lipiodol (2016+/-92 MBq). For the nuclear medicine specialists, 52 measurements were carried out at the level of the thorax and 41 on the fingers. For the radiologists, 22 measurements were carried out at the level of the thorax and six on their index fingers; nine measurements were carried out at the level of the thorax for the technologist and four at the level of the thorax for the stretcher bearer. For the nuclear medicine specialists, the average dose received at the level of the fingers varies between 140 and 443 microSv (according to the fingers) and the average dose at the thorax is 17 microSv. For the radiologists, the average dose received is 215 microSv at the level of the fingers and 15 microSv at the thorax. These results show that the administration of high therapeutic activities of 131I-lipiodol can be carried out for the exposed personnel with a dose at the level of the fingers much lower than the European regulatory limit of 500 mSv.
Subject(s)
Carcinoma, Hepatocellular/radiotherapy , Iodine Radioisotopes/administration & dosage , Iodine Radioisotopes/analysis , Occupational Exposure/prevention & control , Radiation Dosage , Radiation Injuries/prevention & control , Radiation Protection/instrumentation , Radiation Protection/methods , Film Dosimetry , Fingers , Health Personnel , Humans , Injections, Intra-Arterial/instrumentation , Injections, Intra-Arterial/methods , Iodine Radioisotopes/adverse effects , Iodized Oil/administration & dosage , Iodized Oil/adverse effects , Iodized Oil/analysis , Liver Neoplasms/radiotherapy , Nuclear Medicine , Radiation Injuries/etiology , Radiopharmaceuticals/administration & dosage , Radiopharmaceuticals/adverse effects , Radiopharmaceuticals/analysis , Risk Assessment/methods , Thermoluminescent Dosimetry , ThoraxABSTRACT
PURPOSE: To assess antitumor activity and safety of two regimens in advanced colorectal cancer (CRC) patients with proven fluorouracil (5-FU) resistance in a randomized phase II study: 5-FU/folinic acid (FA) combined with alternating irinotecan (also called CPT-11) and oxaliplatin (FC/FO tritherapy), and an oxaliplatin/irinotecan (OC) combination. PATIENTS AND METHODS: Sixty-two patients were treated: arm FC/FO (32 patients) received, every 4 weeks, FA 200 mg/m(2) followed by a 400-mg/m(2) 5-FU bolus injection, then a 600-mg/m(2) continuous infusion of 5-FU on days 1 and 2 every 2 weeks administered alternately with irinotecan (180 mg/m(2) on day 1) and oxaliplatin (85 mg/m(2) on day 15). Arm OC (30 patients) received oxaliplatin 85 mg/m(2) and irinotecan 200 mg/m(2) every 3 weeks. RESULTS: In an intent-to-treat analysis, two partial responses lasting 10.7 and 16 months were observed with the tritherapy regimen, and seven (median duration, 11 months; range, 10.6 to 11.4 months) were observed with the bitherapy regimen. Median progression-free and overall survival times were 8.2 and 9.8 months, respectively, in the FC/FO arm and 8.5 and 12.3 months, respectively, in the OC arm. Main grade 3/4 toxicities were, respectively, neutropenia, 53% and 47%; febrile neutropenia, 13% and 3%; diarrhea, 19% and 10%; vomiting, 6% and 13%; and neurosensory toxicity, 3% and 3%. No treatment-related deaths occurred. CONCLUSION: The every-3-weeks OC combination is safe and active in advanced 5-FU-resistant CRC patients. The lower activity data seen with the tritherapy regimen may be related to the lower dose intensities of irinotecan and oxaliplatin in this schedule.
Subject(s)
Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Camptothecin/analogs & derivatives , Colonic Neoplasms/drug therapy , Rectal Neoplasms/drug therapy , Adult , Aged , Camptothecin/administration & dosage , Chemotherapy, Adjuvant , Colonic Neoplasms/mortality , Colonic Neoplasms/secondary , Drug Administration Schedule , Female , Fluorouracil/administration & dosage , Humans , Irinotecan , Leucovorin/administration & dosage , Male , Middle Aged , Organoplatinum Compounds/administration & dosage , Oxaliplatin , Rectal Neoplasms/mortality , Rectal Neoplasms/secondary , Survival Rate , Treatment OutcomeSubject(s)
Medical Oncology/methods , Nuclear Medicine/methods , Tomography, Emission-Computed/methods , Carcinoma, Hepatocellular/radiotherapy , Contraindications , Contrast Media/therapeutic use , Fluorodeoxyglucose F18 , Humans , Iodine Radioisotopes/therapeutic use , Iodized Oil/therapeutic use , Liver Neoplasms/radiotherapy , Lymphatic Metastasis/diagnostic imaging , Neoplasms/diagnostic imaging , Neoplasms/radiotherapy , Radioimmunotherapy/methods , RadiopharmaceuticalsABSTRACT
We conducted a prospective study on neoadjuvant treatment for squamous cell carcinoma of the esophagus, modifying the chemotherapy protocol by adding l-folinic acid and giving bifractionated radiotherapy with a cis-diaminedichloroplatinum (CDDP) injection before each fraction. Thirty-two patients, 30 men, 2 women, mean age 56.2-8.9 years, with resectable squamous celi carcinoma of the esophagus (TNM stage I = 4, IIA = 4, IIB = 13, III = 11) were included. Chemotherapy, CDDP (80 mg/m2: D2), 5-fluorouracil (5-FU; 600 mg/m2, D1-4), and 1-folinic acid (200 mg/m2, DI-4), was given in two sessions with a 3-week interval during which the patients received radiotherapy (45 Gy), two fractions per day (150 cGy/fraction). A 3-mg Injection of CDDP was given prior to each fraction. Patients underwent surgery 4 to 7 weeks after neoadjuvant therapy. No severe side effects were observed in 12 patients. Grade 3 effects (WBC, platelests, mucosite's) occurred in 16 patients and grade 4 effects (platelets, mucositis) in four including 1 death due to septicemia with an infected catheter. Surgery was performed in 29 patients; 26 had resectable tumors (81%). Operative mortality was 10%. The 26 surgical specimens showed complete response (n = 18), persistent microscopic residues (n = 4), or not significant modification (n = 4). Survival at 1, 3, and 5 years was 82, 47, and 47% and disease-free survival was 77, 47, and 47% respectively. This new therapeutic combination is aggressive and associated with a high postoperative mortality but has a remarkable histological effect since complete response was achieved in 56% (95% CI: 39-73%) of the patients and 5-year survival reached 47%, a very high rate in our experience.
Subject(s)
Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Carcinoma, Squamous Cell/drug therapy , Carcinoma, Squamous Cell/surgery , Esophageal Neoplasms/drug therapy , Esophageal Neoplasms/surgery , Esophagectomy , Neoadjuvant Therapy/methods , Carcinoma, Squamous Cell/mortality , Carcinoma, Squamous Cell/pathology , Cisplatin/administration & dosage , Esophageal Neoplasms/mortality , Esophageal Neoplasms/pathology , Female , Fluorouracil/administration & dosage , Humans , Leucovorin/administration & dosage , Male , Middle Aged , Neoplasm Staging , Prospective Studies , Radiotherapy Dosage , Radiotherapy, Adjuvant , Survival Analysis , Treatment OutcomeABSTRACT
PURPOSE: We conducted a prospective study of neoadjuvant treatment for squamous cell carcinoma of the esophagus, modifying the chemotherapy protocol by adding l-folinic acid and giving bifractionated radiotherapy with a cis-diaminedichloroplatinum (CDDP) injection before each fraction. METHODS AND MATERIALS: Thirty-two patients, 30 men, 2 women, mean age 56.2+/-8.9 years, with resectable squamous cell carcinoma of the esophagus (TNM stage I=4, IIA=4, IIB=13, III=11) were included. Chemotherapy, CDDP (80 mg/m2 D2), 5-fluorouracil (5-FU; 600 mg/m2, D1-4), and l-folinic acid (200 mg/m2, D1-4), was given in two sessions with a 3-week interval during which the patients received radiotherapy (45 Gy), two fractions per day (150 cGy/fraction). A 3-mg injection of CDDP was given prior to each fraction. Patients underwent surgery 4 to 7 weeks after neoadjuvant therapy. RESULTS: No severe side effects were observed in 12 patients. Grade 3 effects (WBC, platelets, mucositis) occurred in 16 patients and grade 4 effects (platelets, mucositis) in four including 1 death due to septicemia with an infected catheter. Surgery was performed in 29 patients; 26 had resectable tumors (81%). Operative mortality was 10%. The 26 surgical specimens showed complete response (n=18), persistent microscopic residues (n=4), or not significant modification (n=4). Survival at 1, 2, and 3 years was 81, 61, and 51.6% and disease-free survival was 75, 59, and 54% respectively. CONCLUSIONS: This new therapeutic combination is aggressive and associated with a high postoperative mortality but has a remarkable histological effect since complete response was achieved in 56% (95% CI: 39-73%) of the patients and 3-year survival reached 52%, a very high rate in our experience.
Subject(s)
Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Carcinoma, Squamous Cell/drug therapy , Carcinoma, Squamous Cell/radiotherapy , Esophageal Neoplasms/drug therapy , Esophageal Neoplasms/radiotherapy , Antidotes/administration & dosage , Carcinoma, Squamous Cell/mortality , Chemotherapy, Adjuvant , Cisplatin/administration & dosage , Esophageal Neoplasms/mortality , Female , Fluorouracil/administration & dosage , Humans , Leucovorin/administration & dosage , Male , Middle Aged , Prospective Studies , Radiotherapy Dosage , Treatment OutcomeABSTRACT
Chemoembolisation has been extensively used as primary treatment for unresectable hepatocellular carcinoma (HCC). In this unit, 185 patients with a new diagnosis of HCC not amenable to surgery were seen between 1988 and 1991. Intended therapy for these patients was chemoembolisation with doxorubicin (60 mg/m2) and lipiodol, repeated at six week intervals until it was technically no longer possible or until complete tumour response had been obtained. Chemoembolisation was possible in 67 of the 185 (37%). Reasons for exclusion were portal vein occlusion (n = 36), decompensated cirrhosis (n = 44), distant metastases (n = 5), diffuse tumour or unsuitable anatomy (tumour or vasculature) (n = 11), patient refusal (n = 11), and other (n = 11). Patients excluded from treatment survived for a median of 10 weeks (range 3 days-19 months). In patients treated, 18 had small HCC (4 cm) and 49 had large or multifocal HCC. Chemoembolisation was carried out a median of two sessions for small and three sessions for large tumours. Ten of 18 patients with small HCC showed a 50% or greater reduction in tumour size. Five of 49 patients with large or multifocal tumours showed a response to treatment. Median overall survival for treated patients was 36 weeks (range 3 days-4 years). One patient has subsequently undergone liver transplantation with no recurrence and minimal residual disease at transplantation. Two other patients are alive three years after chemoembolisation, one with no evidence of recurrent disease. No patient was thought suitable for surgery after their response to chemoembolisation. Chemotherapy related complications were seen in 22%. Complications were significantly more common in patients with larger tumours and poor liver reserve. Five patients died as a result of chemotherapy related complications. In conclusion, only one third of UK patients with unresectable HCC are treatable by chemoembolisation. Results with small tumours are encouraging, with a high response rate and the possibility of surgical intervention in previously inoperable disease. Large tumours, however, show a poor response and significant incidence of side effects, suggesting that this treatment offers little benefit in advanced disease.
Subject(s)
Antibiotics, Antineoplastic/administration & dosage , Carcinoma, Hepatocellular/therapy , Chemoembolization, Therapeutic , Contrast Media/administration & dosage , Doxorubicin/administration & dosage , Iodized Oil/administration & dosage , Liver Neoplasms/therapy , Clinical Trials as Topic , HumansABSTRACT
Intra-arterial injection of radioactive Lipiodol has shown promising results in patients with hepatocellular carcinoma (HCC) and portal obstruction. The aim of this prospective, randomized trial was to compare the efficacy and tolerance of 131I-labeled Lipiodol and chemoembolization for the treatment of patients with HCC. From September 1990 to September 1993, 142 patients (135 men, 7 women; age: 65 +/- 6.6 years) were randomly assigned to treatment groups and given either intra-arterial injections of 131I-labeled Lipiodol (60 mCi; 2.2 GBq) (n = 73) or chemoembolization (70 mg cisplatin) (n = 69). Subsequent injections were given at 2, 5, 8, 12, and 18 months. Tumor response was assessed on the basis of tumor size and serum alpha-fetoprotein levels. Patient tolerance was assessed clinically and angiographically. Survival rate was the main end-point. A total of 129 patients (65 in the 131I-labeled Lipiodol group and 64 in the chemoembolization group) were available for analysis; 13 were excluded, mainly because of portal vein thrombosis. The two groups were comparable. Actuarial survival curves were not significantly different between the two groups. Overall survival rates at 6 months, 1, 2, 3, and 4 years were 69%, 38%, 22%, 14%, and 10%, and 66%, 42%, 22%, 3%, and 0% in the 131I-labeled Lipiodol and chemoembolization groups, respectively. Reduction in tumor size was similar for the two groups, with complete response in 1 and 0 patients and partial response in 15 and 16 patients in the 131I-labeled Lipiodol and chemoembolization groups, respectively. Tolerance was significantly better in the 131I-labeled Lipiodol group both clinically (3 severe side effects vs. 29 in the chemoembolization group; P < .001) and angiographically (1 arterial thrombosis vs. 10 in the chemoembolization group; P < .01). In terms of patient survival and tumor response, radioactive 131I-labeled Lipiodol and chemoembolization were equally effective in the treatment of HCC, but tolerance to 131I-labeled Lipiodol was significantly better.
Subject(s)
Carcinoma, Hepatocellular/therapy , Embolization, Therapeutic , Iodized Oil/therapeutic use , Liver Neoplasms/therapy , Aged , Cisplatin/administration & dosage , Cisplatin/therapeutic use , Embolization, Therapeutic/adverse effects , Emulsions , Female , Follow-Up Studies , Humans , Injections, Intra-Arterial , Iodine Radioisotopes , Iodized Oil/administration & dosage , Iodized Oil/adverse effects , Male , Middle Aged , Prospective Studies , Sodium Chloride/administration & dosage , Sodium Chloride/therapeutic use , Survival Analysis , Treatment OutcomeABSTRACT
The authors report the case of a cirrhotic patient with a multinodular hepatocellular carcinoma. Two nodules were located in the right liver lobe and a minute nodule was in the left lobe. Because of poor liver function, two injections of iodine-131-labeled Lipiodol were delivered in the right hepatic artery to protect the left lobe. The efficacy was obvious in the treated areas, but the minute lesion enlarged dramatically and was responsible for the patient's death.
Subject(s)
Carcinoma, Hepatocellular/therapy , Chemoembolization, Therapeutic/methods , Contrast Media , Iodine Radioisotopes/administration & dosage , Iodized Oil/administration & dosage , Liver Neoplasms/therapy , Aged , Carcinoma, Hepatocellular/diagnostic imaging , Contrast Media/administration & dosage , Contrast Media/therapeutic use , Hepatic Artery , Humans , Injections, Intra-Arterial , Iodine Radioisotopes/therapeutic use , Iodized Oil/therapeutic use , Liver Neoplasms/diagnostic imaging , Male , Radionuclide Imaging , Tomography, X-Ray ComputedABSTRACT
UNLABELLED: Portal vein thrombosis is a poor prognostic factor in patients with hepatocellular carcinoma (HCC) and a contraindication for chemoembolization. Intra-arterial injection of 131I-iodized oil which does not modify arterial flow, is feasible in this condition. The aim of this prospective randomized controlled trial was to compare the efficacy of treatment with radiolabeled oil (treated group) versus medical support (control group) in patients with stage I or II HCC (classification of Okuda) with portal vein thrombosis. METHODS: Twenty-seven HCC patients (26 males, 1 female), aged 53-79 yr, with portal vein thrombosis were randomly assigned to Lipiocis group (n = 14) or Control group (n = 13). Additional injections of radiolabeled oil were given 2, 5, 8 and 12 mo after initial therapy. Medical support treatment consisted of: tamoxifen (n = 5), 5 FU intravenously (n = 1), NSAIDs or corticosteroids (n = 5). Efficacy was evaluated according to survival rate (Kaplan-Meier method; log rank test), AFP serum values (measured at 2, 5, 8 and 12 mo) and angiography. RESULTS: The two groups were comparable (Child's classification, Okuda's classification, liver function tests, location of the thrombus). Tolerance was excellent in the Treated group. The actuarial survival curves were significantly different (p < 0.01) between the two groups, the survival rates (Cl 95%) at 3, 6 and 9 mo being 71% (48%-95%), 48% (12%-55%), 7% (1%-31%) for the Treated group; and 10% (1%-33%), 0% and 0% for the Control group. CONCLUSION: Intra-arterial hepatic injection of 131I-labeled iodized oil is a safe and effective palliative treatment of HCC with portal vein thrombosis.
Subject(s)
Carcinoma, Hepatocellular/radiotherapy , Iodine Radioisotopes/therapeutic use , Iodized Oil/therapeutic use , Liver Neoplasms/radiotherapy , Neoplastic Cells, Circulating , Palliative Care/methods , Portal Vein , Adrenal Cortex Hormones/therapeutic use , Aged , Anti-Inflammatory Agents, Non-Steroidal/therapeutic use , Carcinoma, Hepatocellular/drug therapy , Carcinoma, Hepatocellular/mortality , Female , Fluorouracil/therapeutic use , Hepatic Artery , Humans , Injections, Intra-Arterial , Iodine Radioisotopes/administration & dosage , Iodized Oil/administration & dosage , Liver Neoplasms/drug therapy , Liver Neoplasms/mortality , Male , Middle Aged , Prospective Studies , Survival Rate , Tamoxifen/therapeutic useSubject(s)
Diarrhea/chemically induced , Plant Extracts/adverse effects , Aged , Chronic Disease , Female , HumansABSTRACT
This study assesses the usefulness of intra-arterial injection of iodized oil (Lipiodol) as a tool for evaluating the therapeutic choice in a series of 72 consecutive patients with hepatocellular carcinoma (HCC). In 52 of these patients a scintigraphic study of the biodistribution of iodized oil was done, using 131I-iodized oil injection. A single tumor was detected in only 17 cases; 18 patients had a tumor involving only 1 lobe; in 7 cases CT scan disclosed a minute nodule in the opposite lobe of the main tumor. Eighteen patients had a portal thrombosis; in 12 of these cases CT scan showed iodized oil in the tumor emboli. The degree of intratumoral retention of iodized oil depended on the size of tumors and on the presence of arterioportal shunts. Our study demonstrates that only a few patients (4%) with HCC might benefit from curative surgery. The therapeutic benefit of methods using iodized oil injection might be estimated by means of its biodistribution variables (CT and/or scintigraphic data).
Subject(s)
Carcinoma, Hepatocellular/diagnostic imaging , Iodine Radioisotopes , Iodized Oil , Liver Neoplasms/diagnostic imaging , Adult , Aged , Carcinoma, Hepatocellular/surgery , Female , Hepatectomy , Humans , Liver Neoplasms/surgery , Male , Middle Aged , Palliative Care , Portal Vein/diagnostic imaging , Prospective Studies , Radionuclide Imaging , Thrombosis/diagnostic imaging , Tomography, X-Ray ComputedABSTRACT
BACKGROUND: This study evaluated the effects of an association of ethiodized oil (Lipiodol Ultra Fluide, Laboratoires Guerbet, Aulnay-sous-Bois, France), with or without gelatin sponge, with doxorubicin (Adriamycin, Adria Laboratories, Columbus, OH) on the biodistribution and kinetics of doxorubicin during intraarterial injection. METHODS: Eighteen patients with hepatocellular carcinoma on cirrhotic liver received a therapeutic injection into the hepatic artery of 50 mg of doxorubicin alone (Group 1; n = 4), or emulsified in 10 ml of ethiodized oil and 2.5 ml of ioxaglate (Hexabrix, Laboratoires Guerbet) with (Group 2; n = 7) or without (Group 3; n = 7) gelatin sponge embolization. Before treatment, the absence of intrahepatic shunts was verified by an injection of technetium-labeled albumin macroaggregates. The biodistribution of doxorubicin was studied on two fronts: (1) pharmacokinetic--by measurement of the doxorubicin blood level during the 48 hours after injection; and (2) scintigraphic (2 mg of doxorubicin were labeled with 2 mCi of iodine 131)--by examination of the scintigrams and calculation of the following parameters: tumours liver/nontumorous liver binding ratio (T/NT ratio), liver/liver+lungs+abdomen binding ratio, and doxorubicin half-life in tumorous tissue. RESULTS: Pharmacokinetics results showed the following: the peak plasma concentration was significantly higher in Group 1 as compared with Groups 2 or 3 (Group 1: 2.1 +/- 0.9 mg/ml; Group 2: 0.9 +/- 0.3 mg/ml; Group 3: 0.5 +/- 0.2 mg/ml); the area under curve calculated from time zero to 1 hour was lower in Groups 2 and 3 compared with Group 1. Examination of the scintigrams showed the following: diffuse activity throughout the organism (Group 1), diffuse activity with strong hepatic and tumorous binding (Group 2), and mostly hepatic and tumoral binding (Group 3). The liver/liver+lungs+abdomen binding ratio was 28% +/- 1% in Group 1, 36% +/- 5% in Group 2, and 63% +/- 7% in Group 3. The T/NT ratios were 1.0 +/- 0 (Group 1), 1.5 +/- 0.1 (Group 2), and 4.7 +/- 0.5 (Group 3). The doxorubicin half-lives in tumourous tissue were 0.7 +/- 0.1 days (Group 1), 1.8 +/- 0.2 days (Group 2), and 2.6 days (n = 1; Group 3). CONCLUSIONS: This study shows (1) that the association of ethiodized oil with doxorubicin lowers the peak concentration of doxorubicin and increases the intratumoral concentration and half-life of doxorubicin, and (2) that these kinetic ameliorations are even more pronounced after embolization. Therefore, from a kinetic standpoint, the doxorubicin-ethiodized oil-gelatin sponge association is the best.