Intensive treatment of renal failure in patients with myeloma

Summary. We have reviewed our experience in the management of myeloma patients who present with features of severe renal impairment, to examine the role of intensive treatment of the renal failure, and to assess the role of renal biopsy. Between March 1983 and August 1991, 16 patients, who were subsequently diagnosed as having myeloma, presented to the Department of Renal Medicine for investigation of renal failure; nine with symptoms of uraemia and seven with pneumonia, bone pain, emphysema, or ischaemic heart disease. Renal biopsy was performed on 14 patients. Eleven patients had myeloma cast nephropathy, two of whom had concurrent hypertensive nephropathy, two patients had light chain deposition disease, and one patient had interstitial nephritis. Renal function improved in six patients with aggressive rehydration, but three of them subsequently required dialysis. In all 11 patients required dialysis, two short-term and nine long-term. Seven patients were given conventional melphalan and prednisolone and nine patients received VAMP as induction cytotoxic chemotherapy. Five of the VAMP sub-group received interferon α2b as maintenance therapy. The median renal survival was five months (range 0–36 months) and median overall survival was 20 months (range 1–54 months). We conclude that intensive treatment, including dialysis, in myeloma patients with renal failure may result in survival durations approaching those of unselected myeloma patients, and a significant proportion will enjoy a reasonable quality of life.     

Laparoscopic resection of hepatic colorectal metastases

BackgroundLiver resection for secondary malignancy has become the standard of care in appropriately staged patients, offering 5-year survival rates of >40%. Reports of laparoscopic liver resection have been published with increasing frequency over the last few years. In these small series approximately one-third of all operations have been for malignancy, but survival figures cannot be assessed yet.MethodsA retrospective review of all laparoscopic liver resections performed by four surgeons in Brisbane between 1997 and 2004 was done. Follow-up was by regular patient review and telephone confirmation.ResultsOf 84 laparoscopic liver resections, 33 (39%) were for malignancy; 28 of these were for metastases (22 colorectal). Thirteen patients had left lateral sectionectomy with minimal morbidity; nine right hepatectomies were attempted and six cases of segmental or subsegmental resection were performed. Survival rates in 12 patients followed for 2 years with colorectal secondaries were 75% with 67% disease-free.DiscussionLaparoscopic liver resection is feasible in highly selected cases of malignant disease. Patients need to be appropriately staged and surgeons need a broad experience of open liver surgery and advanced laparoscopic procedures.     

Patients with multiple synchronous colonic cancer hepatic metastases benefit from enrolment in a “liver first” approach protocol

AIM: To assess a protocol for treating patients with multiple synchronous colonic cancer liver metastases, which are unresectable in one stage. METHODS: Patients enrolled in the "liver first" protocol presented with colon-only(not rectal) cancer and multiple synchronous hepatic metastases(type Ⅱ or Ⅲ). All patients showed good performance status(ECOG PS 0-1) and were treated with curative intent. Complete oncologic staging including positron emission tomography-computed tomography was performed in order to rule out extrahepatic disease. If bowel obstruction was imminent, an intraluminal colonic stent was placed endoscopically. Subsequently, all patients received standardised neo-adjuvant chemotherapy, that is, FOLFOX or XELOX regimens combined with an antiangiogenic agent(bevacizumab or cetuximab). Provided that a response to chemotherapy was observed, patients underwent either one or two hepatectomies with or without portal vein embolization followed by the indicated colectomy. Further chemotherapy was administered after each procedure. Re-staging was performed after each chemotherapeutic treatment. Disease progression at any stage resulted in discontinuation of the protocol and conversion to palliative disease management.RESULTS: Prospectively recorded data from 11 consecutive patients(8 men) were analysed for this study. Their mean age at the time of their first assessment was 65.7(SD ± 15.3) years. Six(54.6%) patients presented with type Ⅲ metastatic disease. The minimum and maximum follow-up periods were 7.3 and 39.6 mo, respectively. The mean overall survival of all patients was 16.5(95%CI: 10.0-23.2) mo. A colonic stent had to be placed in 5(45.5%) patients due to the onset of an intraluminal obstruction. Four(36.4%) patients succeeded in completing all planned surgical operations. Their mean overall survival was 27.2(95%CI: 15.1-39.3) mo and the mean disease-free survival was 7.7(95%CI: 3.0-12.5) mo. Patients, who were obliged to shift to palliative treatment due to dis-ease progression, had a mean overall survival of 10.5(95%CI: 8.6-12.4) mo. None of these patients underwent palliative colectomy. No postoperative mortality was recorded.CONCLUSION: The implementation of a structured "liver first" approach protocol for the treatment of patients with extensive, liver-limited colon cancer metastatic disease may be beneficial.     

Interaction of thoracic irradiation and chemotherapy on local control and survival in small cell carcinoma of the lung.

The records of all patients with small cell carcinoma of the lung seen in the Division of Therapeutic Radiology at The Medical College of Wisconsin from 1971 through 1977 were reviewed. Of 69 patients (34 with limited disease and 35 with extensive disease), 35 received irradiation only, nine received local plus total-body irradiation, and 25 received irradiation plus chemotherapy. In spite of the prompt response of the tumor, 16 of 35 patients who were only irradiated failed locally. Two patients who received local plus total-body irradiation failed in the chest. Only four of 25 irradiation plus chemotherapy patients failed locally in spite of much lower doses of thoracic irradiation. Limited-disease patients who had local control by irradiation had a slight increase (29 vs 22 weeks) in median survival. Patients receiving irradiation plus chemotherapy (three with limited and 22 with extensive disease) survived for a median of 56 weeks if the local tumor was controlled and for a median of 28 weeks if there was local failure. Regardless of therapy, survival beyond the median is greatly influenced by local tumor control.     

Combined valve replacement and coronary bypass surgery. Results in 127 operations stratified by surgical risk factors

The results of 127 operations with both valve replacement and coronary bypass were compared with all 5,053 operations involving coronary bypass performed from August 1972 through June 1985. Both groups were stratified by the number of risk factors (age over 70 years, bad ventricle, extensive endarterectomy, and reoperation). Compared with all bypass operations, valve replacement had no effect on surgical mortality except in the group at highest risk. Conversely, valve replacement was associated with reduced late survival in all but those at highest risk. Results with tissue valves were better than with mechanical, but statistical significance was lacking. Relief of angina was equal. Ischemic mitral insufficiency continues to be the greatest challenge, with 46 percent five-year survival. We conclude that combined valve replacement and bypass surgery can be performed successfully, even in the patients at higher risk; however, this operation should be performed only by teams with demonstrated success in surgically treating advanced coronary artery disease.     

Intraoperative radiation therapy for pancreatic adenocarcinoma: the Komagome hospital experience

We analyzed 144 patients with pancreatic adenocarcinoma who had received intraoperative radiation therapy (IORT) in combination with external beam radiation therapy (EBRT) within the past 20 years. The patients were divided into 2 groups: group 1 contained 65 patients with locally unresectable tumors who underwent bypass operations and group 2 contained 68 patients with resectable tumors who underwent pancreatic resection. As a pilot study, we performed additional arterial infusion chemotherapy after changing peripancreatic hemodynamics during EBRT in the remaining 11 patients. The 30 patients who received R0 resection had the best survival rates (3-year survival rate of 35.4%), while 3 patients with stage III disease survived more than 5 years. The survival of group 1 patients nearly equaled that of group 2 patients who underwent R1 or R2 resection (median survival, 10.9 vs. 11.1 months, respectively; P = 0.43). The 1-year survival rate for the 11 patients receiving arterial infusion chemotherapy was 45.4%, and 5 patients survived over 1 year without developing hepatic metastasis or regrowth of primary tumors. The survival benefits obtained using this form of radiotherapy are apparently limited. On the other hand, additional arterial infusion chemotherapy employing a new drug delivery system using hemodynamic change does appear promising.     

Management of hilar cholangiocarcinoma in the North of England： Pathology, treatment, and outcome

AIM: To assess the management and outcome of hilar cholangiocarcinoma (Klatskin tumor) in a single tertiary referral center. METHODS: The notes of all patients with a diagnosis of hilar cholangiocarcinoma referred to our unit for over an 8-year period were identified and retrospectively reviewed. Presentation, management and outcome were assessed. RESULTS: Seventy-five patients were identified. The median age was 64 years (range 34-84 years). Male to female ratio was 1:1. Eighty-nine percent of patients presented with jaundice. Most patients referred were under Bismuth classification 3a, 3b or 4. Seventy patients required biliary drainage, 65 patients required 152 percutaneous drainage procedures, and 25 had other complications. Forty-one patients had 51 endoscopic drainage procedures performed (15 failed). Of these, 36 subsequently required percutaneous drainage. The median number of drainage procedures for all patients was three, 18 patients underwent resection (24%), nine had major complications and three died post-operatively. The 5-year survival rate was 4.2% for all patients, 21% for resected patients and 0% for those who did not undergo resection (P = 0.0021). The median number of admissions after diagnosis in resected patients was two and three in non-resected patients (P<0.05). Twelve patients had external-beam radiotherapy, seven brachytherapy, and eight chemotherapy. There was no significant benefit in terms of survival (P = 0.46) or hospital admissions. CONCLUSION: Resection increases survival but carries the risk of significant morbidity and mortality. Percutaneous biliary drainage is almost always necessary and endoscopic drainage should be avoided if possible.     

Prognostic factors in patients with advanced cholangiocarcinoma： Role of surgery, chemotherapy and body mass index

AIM： To study the factors that may affect survival of cholangiocarcinoma in Lebanon. METHODS： A retrospective review of the medical records of 55 patients diagnosed with cholangio- carcinoma at the American University of Beirut between 1990 and 2005 was conducted. Univariate and multivariate analyses were performed to determine the impact of surgery, chemotherapy, body mass index, bilirubin level and other factors on survival. RJ~SULTS： The median survival of all patients was 8.57 mo （0.03-105.2）. Univariate analysis showed that low bilirubin level （〈 10 mg/dL）, radical surgery and chemotherapy administration were significantly associated with better survival （P = 0.012, 0.038 and 0.038, respectively）, in subgroup analysis on patients who had no surgery, chemotherapy administration prolonged median survival significantly （17.0 mo vs 3.5 mo, P = 0.001）. Multivariate analysis identified only low bilirubin level 〈 10 mg/dL and chemotherapy administration as independent predictors associated with better survival （P 〈 0.05）. CONCLUSION： Our data show that palliative and postoperative chemotherapy as well as a bilirubin level 〈 10 mg/dL are independent predictors of a significant increase in survival in patients with cholangiocarcinoma.     

Aggressive primary gastrointestinal lymphomas: review of 91 patients treated with the LNH-84 regimen. A study of the Groupe d'Etude des Lymphomes Agressifs.

PURPOSE: Patients with aggressive primary gastrointestinal lymphoma undergoing the LNH-84 chemotherapy regimen were analyzed to determine the efficacy of intensive combination chemotherapy, the role of surgical debulking in patients treated with combination chemotherapy, and the toxicity associated with each of these modalities. PATIENTS AND METHODS: Ninety-one patients with primary gastrointestinal lymphoma who participated in the prospective multicenter LNH-84 combination chemotherapy trial (total number of patients in trial, 737) were analyzed. These 91 patients included 69 (76%) with diffuse large cell, nine (10%) with diffuse mixed, and seven (8%) with small noncleaved cell lymphoma. Two patients (2%) had stage IE, 54 patients (59%) stage IIE, and 35 patients (38%) stage IV disease; all patients with stage IE, 22 with stage IIE, and 18 with stage IV disease had bulky (greater than or equal to 10 cm) tumors. Specific sites of gastrointestinal involvement included stomach (47%), small bowel (38%), ileocecum (14%), colon (11%), and rectum (7%). Although surgical resection was attempted in 71 patients (78%), only 28 (31%) had complete tumor excision. All patients received three or four cycles of ACVB (defined in text) induction therapy followed by sequential consolidation as previously described. RESULTS: Responses to treatment in the 91 patients included 71 (78%) complete remissions, six (7%) partial remissions, five (5%) nonresponses, and nine (10%) deaths. With a median follow-up of 3 years, 10 patients (14%) have had relapses; predicted 4-year disease-free survival of complete responders is 85% and predicted 4-year survival of the entire group is 62%. In patients with stage IE or IIE disease, the complete response, survival, and disease-free survival rates were similar in those who underwent complete surgical resection or incomplete or no surgical resection prior to the administration of combination chemotherapy. Prognostic factors predicting for survival in the 91 patients with primary gastrointestinal lymphoma were similar to those in the 646 other patients treated with the LNH-84 regimen. CONCLUSIONS: Patients with aggressive gastrointestinal lymphoma treated with intensive chemotherapy have outcomes and prognostic factors comparable to those of patients with similar-stage aggressive lymphoma without primary gastrointestinal involvement. Surgical resection prior to the administration of combination chemotherapy did not influence the complete response rate, survival rate, or disease-free survival rate in this small group of patients.     

Malignant peritoneal mesothelioma: treatment with maximal cytoreductive surgery plus intraperitoneal chemotherapy

OBJECTIVE: To report survival results in patients with diffuse malignant peritoneal mesothelioma (MPM) treated with maximal cytoreductive surgery followed by immediate intraperitoneal chemotherapy, and to compare them with the median survival of 12-24 months obtained with the standard treatment based on systemic chemotherapy. PATIENTS AND METHODS: Twenty-six patients underwent this new regional approach and a median follow-up of 55 months was achieved after this treatment. Complete cytoreductive surgery (residual disease < 2 mm) was performed in all but one patient. Intraperitoneal chemotherapy was performed with hyperthermia (4245 degrees C) and oxaliplatin in 22 patients. The last 12 patients additionally received irinotecan. Data were prospectively verified and retrospectively analyzed. RESULTS: One patient died postoperatively (4%), and morbidity attained 54%. The median survival exceeded 100 months and the overall 5-year survival rate was 63%. This small series lacks the statistical power required to conduct a well-grounded study on prognostic factors, particularly as the completeness of the surgery is not analyzable here. However, the low-grade histological types had a better disease-free survival rate that was of borderline significance compared to their high-grade counterparts. CONCLUSION: This new approach combining complete cytoreductive surgery considerably increases the survival of patients with MPM compared with the standard treatment based on systemic chemotherapy.     

Evaluation of aggressively treated patients with unresectable multiple liver metastases from colorectal cancer

PURPOSE: The aim of this study was to assess the value of aggressively treating patients with unresectable liver metastases from colorectal cancer and a poor prognosis. METHODS: From 1988 to 1999, 64 patients with unresectable multiple liver metastases from colorectal cancer who had received hepatic arterial infusion chemotherapy were investigated. All patients did not have synchronous extrahepatic metastases at the time of initiating our treatment. When liver metastases were suitable for resection after hepatic arterial infusion chemotherapy, we excised them and repeated prophylactic hepatic arterial infusion chemotherapy as long as possible. We evaluated the efficacy of hepatic arterial infusion chemotherapy by computed tomography and divided these patients into responders and nonresponders. We performed univariate analysis using the log-rank test to calculate predictive factors. In addition, the Cox proportional hazards model was used to perform multivariate analysis of factors related to survival. RESULTS: The survival rate of all patients was 67.8 percent after 1 year and 10 percent after 5 years. However, the survival rate for 16 patients who received hepatectomy after hepatic arterial infusion chemotherapy was 35.1 percent after five years. Multivariate analysis demonstrated that the response after hepatic arterial infusion chemotherapy was the most indicative prognostic factor. CONCLUSIONS: The prognosis of selected patients who responded to hepatic arterial infusion chemotherapy and received hepatectomy was improved. Applying aggressive treatment as outlined in our strategy may improve the chances of long-term survival.     

Patterns of relapse in patients with small cell lung cancer--the effect of chest irradiation and prophylactic cranial irradiation combined with intensive chemotherapy on long-term survival

The pattern of relapse was analyzed in patients with small cell lung cancer (SCLC). Of 180 patients treated with intensive combination chemotherapy between 1976 and 1987, 75 achieved complete response (CR). Of 47 patients with limited disease (LD), 20 (43%) initially relapsed in the chest and 7 (15%) in the brain. Among 27 patients with extensive disease (ED), the chest was also the most frequent site of relapse (44%) followed by the brain (19%). In LD patients who had received chemotherapy plus chest irradiation, the initial relapse rate and the cumulative relapse rate in the chest at 2 years were only 29% and 35.4%, respectively. These rates were significantly lower compared with the rates of 69% and 76.5% for patients who had received chemotherapy alone (p less than 0.05). Survival was improved to some extent by the addition of chest irradiation, but not significantly, however, the long-term survival rate favored those receiving chest irradiation. Prophylactic cranial irradiation (PCI) reduced the frequency of brain relapse and significantly improved the survival of SCLC patients achieving CR. The median survival time and 5-year survival rate of patients who received PCI were 23.1 months and 26.7%, which these figures were only 14.0 months and 8.3% for those who had not respectively. Analysis using Cox's proportional hazard model showed that PCI was the greatest prognostic factor favoring the SCLC patients achieving CR. These results indicate that chest irradiation and PCI in conjunction with intensive combination chemotherapy are effective for cases of SCLC with CR.     

Deleted in Colorectal Cancer Protein Expression as a Possible Predictor of Response to Adjuvant Chemotherapy in Colorectal Cancer Patients

PURPOSE: The deleted in colorectal cancer (DCC) gene predicts a poor outcome for patients with colorectal carcinoma. This study was designed to investigate whether the expression of the DCC protein also can predict response to adjuvant chemotherapy.METHODS: The expression of DCC was evaluated immunohistochemically in 74 paraffin-embedded tumor samples from patients with Stage II (n = 41) and Stage III (n = 33) colorectal carcinomas. Follow-up time was at least 60 (median, 64) months. Follow-up was at least five years for all patients who are alive. End points of the study were recurrence of disease and death. Forty-eight patients received adjuvant therapy of 5-fluorouracil + levamisole; 28 were not treated.RESULTS: Fifty percent of tumors were deleted in colorectal cancer-positive (DCC+). Proportion of survival and disease-free survival were higher in the DCC+ patients (83 percent) than in deleted in colorectal cancer-negative (DCC–; 54 percent). In the DCC+ group, adjuvant treatment was a strong positive predictive factor for survival and disease-free survival. All DCC+ patients who received adjuvant chemotherapy (CHEMO+) are alive with no evidence of disease, whereas without chemotherapy (CHEMO–) only 54 percent are alive (P = 0.0001). When stratification was performed by stage, patients in Stage II who were DCC+/CHEMO+ had survival and disease-free survival of 100 percent, whereas in DCC+/CHEMO– survival rate was 75 percent and disease-free survival rate 62 percent (P = 0.042). Patients in Stage III who were DCC+/ CHEMO+ had survival and disease-free survival of 100 percent, whereas in DCC+/CHEMO– both dropped to zero (P = 0.0002). On the other hand, in the DCC– tumors, there was no statistical significant relationship between chemotherapy and survival or disease-free survival (DCC–/CHEMO– had 57 percent survival; DCC–/CHEMO+ had 52 percent survival).CONCLUSIONS: DCC is a prognostic factor for colorectal cancer. Positive expression of DCC identifies a subgroup of patients who respond favorably to adjuvant chemotherapy, which resulted in our cases, in 100 percent survival and disease-free survival rates. Without treatment, the survival rate of DCC+ patients dropped significantly. We suggest that DCC immunostaining should be performed routinely. All DCC+ patients should receive adjuvant chemotherapy. For DCC– tumors, a larger cohort of patients should be studied before definitive conclusions can be drawn; however, clinical trials of new drug combinations should focus on DCC– patients.Reprints are not available.Supported in part by a grant from the Medical Research Fund of the Rabin Medical Center.Presented in part at the 4th World Congress on Advances in Oncology and 2nd International Symposium on Molecular Medicine, Vouliagmeni, Athens, Greece, October 7 to 9, 1999.     

A new look in the management of unresectable primary hepatocellular carcinoma.

From January 1992 to October 1992, nine patients with unresectable primary hepatocellular carcinoma were treated either by liver resection combined with transarterial on-target chemotherapy (n = 4) or by transarterial on-target chemotherapy alone (n = 5). All nine patients were seen with diffuse spread of their disease and were considered as refractory to surgical treatment. The patients who had liver resection combined with alcohol transtumoral injection of the residual tumor in the liver remnant and transarterial lipiodol on-target chemotherapy, responded well and were seen postoperatively with a significant decrease in size of their residual tumor, which was found histologically to have advanced necrotic changes. Similarly, the remaining patients, who had only alcohol injection and frequent administration of on-target chemotherapy, were seen with necrosis of their tumor and with decrease in its size. The fetoprotein serum levels were decreased in all patients. None of the patients showed systemic effects from the use of chemotherapy, nor did they demonstrate any hepatotoxic side effects.     

Idarubicin and cyclophosphamide--an active oral chemotherapy regimen for advanced breast cancer

Between October 1993 and September 1994, 33 women with metastatic breast cancer aged between 29 and 74 years with a median age of 58 were entered into a study of oral chemotherapy from three UK centres. Patients by definition had metastatic disease and were fit and well with performance status 0 or 1 in 23 cases, 2 in seven cases and 3 in two cases (one missing). Five patients had received prior adjuvant CMF chemotherapy, nine first line non-anthracycline containing chemotherapy for relapse, eight patients second line non-anthracycline containing chemotherapy and all patients had had hormone therapy either as adjuvant or for relapsed disease. Adjuvant radiotherapy had been given to 17 and palliative radiotherapy to 12 patients. In nine patients there was one site of disease at start of therapy, in 10 two sites, in 11 three sites and in three patients four or more sites. The regimen comprised oral idarubicin 15 mg/m2 on day 1, 10 mg/m2 on days 2 and 3 and oral cyclophosphamide 250 mg/m2 (maximum 400 mg) on days 1, 2 and 3. Treatment was continued until disease progression or toxicity. RESULTS: Overall 25% of 32 evaluable patients responded objectively including one complete response; 50% of patients had stable disease and 25% of patients progression. Among patients who had had no prior chemotherapy the objective response rate was 37.5%; 45% of patients had symptomatic improvement. The most common severe toxicity was granulocytopenia WHO grade 3 or more in 69.7% of patients. Thrombocytopenia grade 3 or 4 was seen in four patients. Six patients had documented infections and all but four patients had alopecia. All patients complained of mild or moderate fatigue. Nausea and vomiting occurred in 75% of patients but only four individuals had grade 3 toxicity. Two patients stopped therapy after myocardial infarction and one after impaired cardiac function was noted. The median time to progression was 2.7 months (1-11.5 months) and median survival time 8.8 months (1-13+ months). CONCLUSION: The combination chemotherapy is active in heavily treated patients with manageable toxicity but there are problems in heavily pre-treated patients. There was good compliance in taking medication and at the doses chosen the drugs appear to be suitable for younger fitter patients.     

Clinical experience of pseudomyxoma peritonei in Taiwan with emphasis on the treatment and survival

BACKGROUND/AIMS: Pseudomyxoma peritonei is a rare neoplasm with intra-abdominal gelatinous, jelly-like fluid accumulation. To assess the clinical characteristics, treatment modalities, and predictors of survival of pseudomyxoma peritonei in Chinese patients, we conducted this study. METHODOLOGY: Over a 27-year period, 15 patients with the diagnosis of pseudomyxoma peritonei were enrolled. Their demographic, clinical, treatment and survival data were collected. RESULTS: Seven patients were female and eight were male. The median age at diagnosis was 48 years old for 7 females and 66 years old for 8 males. Exploratory laparotomy and debulking surgery were performed for 11 patients (73%); 6 of these 11 patients received adjuvant chemotherapy. Among 4 patients without surgical treatment, 1 received chemotherapy and 3 had supportive treatment only. The 5-year survival for all patients and patients with surgical treatment were 39% and 62%, respectively. Patients with surgical intervention had longer survival (median, 125 months) than those without surgical treatment (median, 8 months) (P = 0.0106). However, adjuvant chemotherapy did not further prolong the survival time (P = 0.744). CONCLUSIONS: Surgical intervention rather than adjuvant chemotherapy appears to provide a longer survival for patients with pseudomyxoma peritonei.     

Autologous marrow transplantation for patients with chronic myelogenous leukemia (CML) in blast crisis

Eleven patients with chronic myelogenous leukemia (CML) in blast crisis were treated with chemotherapy, followed by infusion of autologous bone marrow that had been collected during the chronic phase of the disease and cryopreserved at ?198°C. The mean age of the nine females and two males in this study was 34 years with an average duration of the chronic phase of the disease of 5.5 years. Seven out of the 11 patients had a splenectomy prior to intensive chemotherapy. The median survival of the first four patients who received 6-thioguanine, cytosine arabinoside, daunorubicin (TAD) chemotherapy was 2.6 weeks and no patient reachieved the chronic phase of CML. The second group of seven patients received more intensive chemotherapy (MAdHAT), which included melphalan 30 mg/m² days 1, 2, and 3; Adriamycin 50 mg/m² intravenously (iv) day 1, hydroxyurea 1500 mg/m² by mouth for 5–7 days, cytosine arabinoside 100 mg/m² continuous infusion for 5–7 days, and VM-26 100 mg/m² iv on day 3. Six out of these seven patients reachieved chronic phase CML after bone marrow reinfusion. The median survival was 29.9 weeks for all patients and 33 weeks for the six patients who reachieved chronic phase CML. All patients subsequently died of recurrent blast crisis. There was no correlation between the time of bone marrow storage and the duration of subsequent chronic phase CML. These studies have shown that autologous bone marrow transplantation after high-dose chemotherapy can result in bone marrow engraftment with reestablishment of chronic phase CML, and prolongation of survival.     

Interferon-alpha before allogeneic bone marrow transplantation in chronic myelogenous leukemia does not affect outcome adversely, provided it is discontinued at least 90 days before the procedure

The influence of interferon-alpha (IFN) pretreatment on the outcome after allogeneic bone marrow transplantation (BMT) in chronic myelogenous leukemia (CML) is controversial. One goal of the German randomized CML Studies I and II, which compare IFN +/- chemotherapy versus chemotherapy alone, was the analysis of whether treatment with IFN as compared to chemotherapy had an influence on the outcome after BMT. One hundred ninety-seven (23%) of 856 Ph/bcr-abl-positive CML patients were transplanted. One hundred fifty-two patients transplanted in first chronic phase were analyzed: 86 had received IFN, 46 hydroxyurea, and 20 busulfan. Forty-eight patients (32%) had received transplants from unrelated donors. Median observation time after BMT was 4.7 (0.7 to 13.5) years. IFN and chemotherapy cohorts were compared with regard to transplantation risks, duration of treatments, interval from discontinuation of pretransplant treatment to BMT, conditioning therapy, graft-versus-host disease prophylaxis and risk profiles at diagnosis and transplantation, and IFN cohorts also with regard to performance and resistance to IFN. Outcome of patients receiving related or unrelated transplants pretreated with IFN, hydroxyurea, or busulfan was not significantly different. Five-year survival after transplantation was 58% for all patients (57% for IFN, 60% for hydroxyurea and busulfan patients). The outcome within the IFN group was not different by duration of prior IFN therapy more or less than 5 months, 1 year, or 2 years. In contrast, a different impact was observed in IFN-pretreated patients depending on the time of discontinuation of IFN before transplantation. Five-year survival was 46% for the 50 patients who received IFN within the last 90 days before BMT and 71% for the 36 patients who did not (P =.0057). Total IFN dosage had no impact on survival after BMT. We conclude that outcome after BMT is not compromised by pretreatment with IFN if it is discontinued at least 3 months before transplantation. Clear candidates for early transplantation should not be pretreated with IFN.     

Systemic cytotoxic and biological therapies of colorectal liver metastases: expert consensus statement

Systemic therapy for colorectal cancer liver metastases (CRLM) has undergone significant development in the past 15 years. Therapy regimens consisting of combinations of cytotoxic chemotherapeutic agents have demonstrated greater efficacy and contributed to a significant survival improvement. As the majority of patients who undergo resection for liver-only CRLM are at risk of disease recurrence and cancer-related death, combining resection with systemic therapy appears sensible. However, trial-based evidence is sparse to support this concept. Peri-operative FOLFOX has demonstrated a progression-free survival benefit in a single Phase III trial; the safety of chemotherapy and subsequent operations was acceptable and only a few patients showed initial progression. Chemotherapy-associated liver injury (CALI), including sinusoidal obstruction syndrome and steatohepatitis, has been observed after cytotoxic therapy, and should have implications for chemotherapy plans prior to hepatectomy. In general, pre-operative chemotherapy should not extend beyond 3 months. For patients with unresectable liver-only CRLM, a response to chemotherapy could establish resectability and should be considered an initial treatment goal. In patients with unresectable CRLM, oxaliplatin- or irinotecan-containing combinations represent the standard options, although single-agent choices may be appropriate for individual patients. The addition of bevacizumab carries the potential for a greater response and possibly for reduced CALI risks. In tumours without K-ras mutations, anti-epidermal growth factor receptor (EGFR) agents are also reasonable choices for a greater response and improved survival outcomes. It is crucial that all systemic CRLM treatment decisions include proper definitions of treatment goals and endpoints, and are derived based on appropriate multidisciplinary considerations for other potentially applicable local or regional modalities.     

Stage IV thymic carcinoma: a study of 20 patients

BACKGROUND: This study was performed to investigate the clinical factors, tumor characteristics, treatment approach, and prognosis of patients with Stage IV thymic carcinoma (WHO type C). METHODS: The records of 20 patients with histologically confirmed thymic carcinoma treated between 1988 and 2002 at the Division of Oncology at Taipei Veterans General Hospital were reviewed. RESULTS: Therapy consisted of surgical debulking, adjuvant radiotherapy, and chemotherapy in six patients (30%), surgical debulking with adjuvant chemotherapy in two patients (10%), surgical debulking with adjuvant radiotherapy in one patient (5%), radiotherapy with adjuvant chemotherapy in eight patients (40%), and chemotherapy alone in three patients (15%). After a median follow-up of 22 months (range, 5-72 months), three patients (15%) were alive. Eighteen patients (90%) experienced disease recurrence after a median of 9 months (range, 2-41 months); 12 (66%) of these patients initially had stage IVa disease, and 6 (33%) had stage IV b disease. Five patients had an undifferentiated type of histology. The median time to progression was 5 months. However, none of these patients was able to receive salvage therapy due to their poor performance status. For those patients with a lymphoepithelioma-like histology, the median survival was 36 months; there was tumor recurrence in five patients and they all received salvage chemotherapy. The median survival time for these five patients was 51 months. For patients with squamous cell type, the median time to progression was 10 months. Five patients received salvage chemotherapy and the median survival was 28 months. There was a significant difference (P < 0.0001) in the median survival between those who received chemotherapy (18 months) after tumor relapse and those who did not (1 month). CONCLUSIONS: Our results indicate that multidisciplinary treatment, including surgery, radiotherapy, and chemotherapy, is beneficial in treating primary thymic carcinoma. Chemotherapy plays an important role in both primary and relapsed stage IV thymic carcinoma in terms of prolonging the disease-free survival and median survival of patients with lymphoepithelioma-like or squamous cell histology types. For patients with an undifferentiated histology, multidisciplinary treatment or chemotherapy might not be helpful in either primary or relapsed stage IV thymic carcinoma.