pⅢA/N2期非小细胞肺癌患者外科治疗的预后分析

Objective: The aim of the study was to identify prognostic factors in non-small-cell lung cancer (NSCLC) with N2nodal involvement. Methods: A retrospective analysis of disease free survival and 5-year survival for NSCLC patients who underwent primary surgical resection without neoadjuvant chemotherapy were performed. Between January 1998 and May 2004, 133 patients were enrolled. Several factors such as age, sex, skip metastasis, number of N2 lymph node stations, type of resection, histology, adjuvant therapy etc., were recorded and analyzed. SPSS 16.0 software was used. Results: Overall 5-year survival for 133 patients was 32.33%, 5-year survival for single N2 station and multiple N2 stations sub-groups were 39.62% and 27.50% respectively, and 5-year survival for cN0-1 and cN2 sub-groups were 37.78% and 20.93% respectively.COX regression analysis revealed that number of N2 station (P= 0.013, OR: 0.490, 95% Cl: 0.427-0.781) and cN status (P =0.009, OR: 0.607, 95% Cl: 0.372-0.992) were two favorable prognostic factors of survival. Conclusion: Number of N2 station and cN status were two favorable prognostic factors of survival. In restrict enrolled circumstances, after combined therapy made up of surgery and postoperative adjuvant therapy have been performed, satisfied survival could be achieved.     

Angiotensin-1-converting enzyme (ACE) gene polymorphism, plasma ACE levels, and their association with the metabolic syndrome and electrocardiographic coronary artery disease in Pima Indians

Although the primary operative mortality following radical hysterectomy for stage IB and early stage IIA cervical carcinoma is less than 1%, survival is poor in those patients with histological evidence of "risk" features--lymph node metastases, lymphatic vascular tumour permeation and clinically undetected parametrial metastases. In the 7-year period 1983 to 1989, 239 patients with stage IB and early IIA disease had radical hysterectomy and pelvic lymphadenectomy. One hundred and eight patients (45.2%) had various poor prognostic histological features and received adjuvant chemotherapy--70 had cisplatin, vinblastine, bleomycin (PVB), 16 had mitomycin C (MMC) and 22 others received mitomycin C + 5-fluorouracil (5-FU). Although not randomised, the risk factors present in each group were identical. These patients have now been followed up for periods ranging from 8 to 14 years. All recurrences, except one, occurred within 23 months of surgery; in the remaining this occurred 8 years later. This suggests that very close long-term follow-up is needed. Recurrences were markedly higher in the group who refused adjuvant chemotherapy (31.6%). The 10-year survival in patients without risk factors was 97.2%. In those patients with risk factors refusing adjuvant therapy it was 73.7%. The adjuvant chemotherapy group had a better survival of 86.1% (P = 0.001). The 10-year survivals in patients with positive nodes were similar--66.7% in the MMC group and 71.4% in the PVB group. The 10-year survival in patients with squamous cell carcinoma was significantly better (90.3%) in the mitomycin C (and MMC + 5-FU) group compared to the PVB group (80.1%) (P = 0.005). The 10-year survival in patients with adenocarcinoma and adenosquamous carcinoma was significantly better (96.3%) in the PVB group compared to those receiving MMC (and MMC + 5-FU) (57.1%) (P = 0.01). It would, thus, appear that the adjuvant chemotherapy of choice for patients with squamous cell carcinoma would be MMC (and MMC + 5-FU) and for those with adenocarcinoma, the PVB regime.     

Value of postoperative radiotherapy in malignant tumors of the upper urinary tract. Apropos of a series of 26 patients

To evaluate the role of adjuvant radiation therapy in invasive transitional cell carcinoma of the upper urinary tract, we retrospectively reviewed a series of 26 patients who underwent radical surgery plus post-operative prophylactic irradiation for such a tumor. Between 1980 and October 1993, 18 men and eight women (mean age: 65 +/- 9 years) were treated for an invasive transitional cell carcinoma of the upper urinary tract. Tumor location was the renal pelvis in 15 patients (58%). The tumor was pathological stage B in 11 patients (42%) and stage C in 15 patients (58%). Tumor grade was 2 in ten patients, 3 in 15 and unknown in one. Nine patients had node involvement. All patients underwent surgery followed by radiation therapy to a total dose of 45 Gy to the tumor bed (23 patients) and/or regional nodes (18 patients). After a mean follow-up of 45 months, 13 patients (50%) were alive and 11 were disease-free. Local tumor relapse, nodal recurrence, metastasis and second urothelial location were noted in one, four (15%), 14 (54%) and eight patients (30%) respectively. Overall 5-year survival and 5-year disease-free survival were 49% and 30% respectively. Overall 5-year survival rates were 60% for stage B and 19% for stage C disease (P = 0.07), 43% for node-negative versus 15% for node-positive cancer (P = 0.04) and 90% for grade 2 and 0% for grade 3 tumors (P < 0.01). In this study using a radio-surgical approach, local control of disease and survival were similar to those reported previously in surgical series. Prophylactic post-operative radiation therapy is not recommended.     

Ki-ras mutation and p53 overexpression predict the clinical behavior of colorectal cancer: a Southwest Oncology Group study

We assessed Ki-ras mutations by single-strand conformation polymorphism followed by DNA sequencing, p53 expression by immunohistochemistry, ploidy status, and S-phase fraction in 66 stage II and 163 stage III colon cancer patients enrolled on a randomized trial of surgery followed by observation or adjuvant levamisole or 5-fluorouracil (5FU) plus levamisole (Intergroup Trial 0035) to see whether these factors were independently associated with survival or with differential effects of adjuvant therapy. A Cox proportional hazards survival model was used to describe marker effects and therapy by marker interactions, with adjustment for the clinical covariates affecting survival. A Bonferroni adjustment was used to account for multiple testing. Mutation of the Ki-ras gene was found in 41% of the cancers and was associated with a poor prognosis in stage II but not stage III. In stage II, 7-year survival was 86% versus 58% in those with wild type versus Ki-ras mutations. After adjustment for treatment and clinical variables, the hazard ratio (HR) for death was 4.5; 95% confidence interval (CI), 1.7-12.1 (P = 0.012). p53 overexpression was found in 63% of cancers and was associated with a favorable survival in stage III but not stage II. Seven-year survival in stage III was 56% with p53 overexpression versus 43% with no p53 expression (HR, 2.2; 95% CI, 1.3-3.6; P = 0.012). Aneuploidy was more common in stage III than in stage II (66 versus 47%; P = 0.009) but was not independently related to survival in either group. The proliferative rate was greater in aneuploid than in diploid cancers but was not related to survival. There was no benefit of adjuvant therapy in stage II nor in any of the stage II subgroups defined by mutational status. In stage III, adjuvant therapy with 5FU plus levamisole improved 7-year survival in patients with wild-type Ki-ras (76 versus 44%; HR, 0.4; 95% CI, 0.2-0.8) and in those without p53 overexpression (64 versus 26%; HR, 0.3; 95% CI, 0.1-0.7). Adjuvant therapy did not benefit those with Ki-ras mutations or p53 overexpression. The effects of adjuvant therapy did not differ according to ploidy status or proliferative rate. Ki-ras mutation is a significant risk factor for death in stage II, and the absence of p53 expression is a significant risk factor for death in stage III colon cancer after adjustment for treatment and clinical covariates. Exploratory analyses suggest that patients with stage III colon cancer with wild-type Ki-ras or no p53 expression benefit from adjuvant 5FU plus levamisole, whereas those with Ki-ras mutations or p53 overexpression do not. An independent study will be required to determine whether response to adjuvant therapy in colon cancer depends on mutational status.     

Comparison of tethered star and linear poly(ethylene oxide) for control of biomaterials surface properties

BACKGROUND: Breast carcinoma in males is infrequent, and information regarding the results of modern treatment is limited. Cases of breast carcinoma in males were accrued from multiple hospitals in one region to determine treatment, survival, and prognostic factors. METHODS: A retrospective review was performed of 217 cases of breast carcinoma in males accessioned at tumor registries of 18 health care institutions in eastern Wisconsin between 1953 and 1995. RESULTS: Of the 217 cases, 215 (99.1%) were carcinomas. The majority of carcinomas were of invasive ductal type and presented as masses. Carcinoma in situ accounted for 5.5% of cases. The 5- and 10-year observed survivals for men were 50.6% and 23.7%, respectively. A high rate of post-treatment mortality from comorbid disease was found. Stage, axillary lymph node status, number of lymph nodes with metastases, and tumor hormone receptors were significant indicators of prognosis. Adjuvant systemic chemotherapy and hormone therapy improved the prognosis of patients with axillary lymph node metastases and hormone receptor positive tumors. Earlier stage at presentation and improved 5-year survival were found in cases occurring between 1986-1995 compared with those occurring in earlier years. Use of modified radical mastectomy and systemic adjuvant therapy also increased since 1986. CONCLUSIONS: The clinical, pathologic, and prognostic features of breast carcinoma in men are similar to those reported for women. The poorer prognosis of men is related to older age at diagnosis, more advanced stage of disease at presentation, and high mortality from comorbid disease. Earlier diagnosis, less radical surgery, and use of systemic adjuvant therapy are coincident with an improved prognosis for men.     

Treatment of breast cancer after 70 years of age. Report of 1143 cases

STUDY AIM: Breast cancer is the most frequent type of cancer in women, increasing in frequency with the elderly. In Europe, a third of new breast cancers occur in women over 70 years of age. The aim of this retrospective study was to analyse the tumoural lesions and therapeutic results in a female population over 70, treated in the same medical centre over a 15-year period. PATIENTS AND METHODS: From 1978 to 1992, 1,143 female patients aged 70 or over were treated for a unilateral breast cancer without metastases and followed-up during a mean 6-year period. The initial treatment was surgical in 1,012 patients: radical mastectomy in 95% of the cases with axillary node dissection in 97.6%. Adjuvant radiotherapy was performed in 289 patients and adjuvant treatment with Tamoxifen in 411 patients. The results were compared with those obtained in 2,947 patients aged 50 to 69, treated during the same period in the same medical centre. RESULTS: The 5-year survival rate in women 70 and over was 80% vs 85.5% in women aged 50 to 69 (P < 0.000001). The same rate of loco-regional recurrences and metastases occurred in both populations. In the patients who initially underwent surgery, after multivariate analysis according to the Cox model, the prognosis factors (similar to those observed in the group of younger women) were: the number of involved nodes (P = 0.000001), the clinical size of the tumour (P = 0.00001), the histological grade (P = 0.01), and the estrogen receptors (P = 0.02). CONCLUSIONS: In this series, the treatment was focused on surgery complemented with adjuvant radiotherapy according to node invasion and adjuvant hormonotherapy according mostly to hormonal receptors. However, the complete treatment could not be applied to all cases: only 50% of patients with node involvement were irradiated. The 5-year survival rate lower than that of younger patients may be attributed to incomplete adjuvant treatment. Specific controlled trials taking into account quality of life had to be undertaken in elderly patients in order to adjust the treatment in relation with the patients' age and physiological condition.     

Effect of UFT on treatment of urological cancer--effect of UFT on treatment of invasive bladder cancer and advanced prostate cancer. Ibaraki Urological Cancer Chemotherapy Study Group

A prospective randomized joint study was conducted to evaluate the usefulness of UFT 1) as a postoperative adjuvant therapy in patients with invasive bladder cancer who had undergone curative combination therapy with operation and/or chemotherapy and/or radiation therapy, 2) as an endocrine chemotherapy in patients with newly diagnosed stage C/D prostate cancer, for a period of 3 years from January, 1992. For bladder cancer, of 36 patients with invasive bladder cancer, clinically cured by combination therapy, 20 patients were treated with UFT as an adjuvant chemotherapy over 12 months, and they were compared to 16 patients with no adjuvant therapy. After excluding 10 inappropriate patients, 12 patients in the UFT treatment group and 14 patients with no adjuvant treatment group were observed. For prostate cancer, of 29 patients with clinically stage C/D prostate cancer, 13 were treated with endocrine therapy in combination with UFT, and 16 patients were treated with endocrine therapy alone. After excluding 7 inappropriate patients, 10 patients with endocrine chemotherapy and 12 patients with hormonal therapy were observed. The non-recurrence rate, survival rate and side effects of UFT were evaluated. In the study of bladder cancer, neither a significant difference of non-recurrent rate nor of survival rate was seen between the two groups. In the study of prostate cancer, neither a significant difference of non-recurrent rate nor of survival rate was seen between the two groups. These findings suggest UFT is less useful as an adjuvant therapy for the invasive bladder cancer and as an endocrine chemotherapy for newly diagnosed advanced prostate cancer.     

Base of tongue carcinoma: patterns of failure and predictors of recurrence after surgery alone

Between January 1971 and December 1986, 55 patients with squamous cell carcinoma of the tongue base underwent complete surgical resection with curative intent. No preoperative or postoperative adjuvant therapy was administered. The study group consisted of 41 men and 14 women (median age 61 years). All patients were followed until death (39 patients) or for a median of 9.4 years. Local control at 5 years was 74%. No predictors of local recurrence were discovered. Control in the dissected neck at 5 years was 68%. Control of cancer above the clavicles at 5 years was 48%. Distant metastases developed in 14% of the patients by 5 years. Cause-specific survival at 5 years was 65%. A Cox multivariate regression analysis revealed that pathologic N stage was the only significant independent predictor of recurrence in the dissected neck, recurrence above the clavicles, and cause-specific survival. The 5-year overall survival was 55%. Surgical mortality was 4%.     

Effects of systemic and regional chemotherapy after hepatic resection for colorectal metastases

BACKGROUND: Although the survival benefit of hepatic resection for colorectal metastasis has been established, some controversy remains regarding the significance of adjuvant chemotherapy after hepatic resection. METHODS: One hundred thirty-two consecutive patients who had liver resection for colorectal metastasis at our hospital between 1980 and 1997 were studied. After curative hepatic resection, 37 patients underwent systemic chemotherapy, administered orally or intravenously, and 38 patients underwent regional chemotherapy, given intra-arterially or intraportally. Forty patients had no adjuvant chemotherapy. The chemotherapeutic agents used for oral administration were uracil and Tegafur or Tegafur alone. Mitomycin C (MMC) or 5-FU was used for IV chemotherapy. Combinations of 5-FU/leucovorin or MMC/5-FU (doxorubicin) were used for regional chemotherapy. Univariate and multivariate analyses were applied to test the significance of adjuvant chemotherapy for patient survival or disease-free survival. RESULTS: Overall 5-year survival was 42.2% (95% CL: 31.2%, 53.2%). Among the possible prognostic factors studied, univariate analysis showed a significant difference in survival based on the number of tumors and lymph node metastases in the hepatic hilum. There was a significant difference in disease-free survival based on adjuvant chemotherapy and lymph node metastasis. The multivariate analysis for patient survival selected four prognostic factors (P < .05), including adjuvant chemotherapy, lymph node metastasis, disease-free interval, and tumor size. The multivariate analysis for disease-free survival selected adjuvant chemotherapy, lymph node metastasis, and disease-free interval as significant factors. The most common recurrence site was remnant liver, regardless of adjuvant chemotherapy. CONCLUSIONS: Adjuvant chemotherapy significantly improved survival and disease-free survival after hepatic resection for colorectal metastases. It did not decrease recurrence rate in the remnant liver.     

Antitumor activity of 1 M tegafur-0.4 M 5-chloro-2,4-dihydroxypyridine-1 M potassium oxonate (S-1) against human colon carcinoma orthotopically implanted into nude rats

The purpose of this study was to establish a nude rat orthotopic (organ-specific) human colorectal cancer model as an in vivo secondary screen for general evaluation of new anticancer agents against colorectal cancer and to evaluate practically the antitumor activity of 1 M tegafur-0.4 M 5-chloro-2,4-dihydroxypyridine-1 M potassium oxonate (S-1), a new p.o. fluoropyrimidine, in comparison to 1 M tegafur-4 M uracil [(UFT) effective on colorectal tumor in clinical]. After implantation of KM12C, a human colorectal cancer cell line, into the subserosal layer of the colon as a single-cell suspension, extensive local tumor growth and invasion to both the mucosal and the serosal sides were observed in all rats. Metastatic foci were also formed in both lymph nodes and lungs following local tumor growth in all of them. Using this method, an equitoxic dose of S-1 (15 mg/kg/day) and UFT (30 mg/kg/day) was administered p.o. for 14 consecutive days from 7 days after tumor cell implantation. S-1 showed a higher tumor growth inhibition than UFT did [S-1, 57% (significantly different from the tumor weight of the untreated group at P < 0.05) and UFT, 18% (P > 0.05)]. When both drugs were administered to nude rats bearing KM12C injected into the cecal wall for 28 consecutive days at equitoxic doses, the mean survival in the S-1 group was 16 days longer than that in the untreated group (P < 0.01) but that in the UFT group was only 8 days longer (P > 0.05). After the administration of an equitoxic dose of both drugs, S-1 gave the higher levels than UFT in various pharmacokinetic parameters as follows: area under the curve 0-24 h of 5-fluorouracil in plasma (3.5-fold), area under the curve 0-24 h of 5-fluorouracil incorporated into RNA in the tumor (1.3-fold), and thymidylate synthase inhibition rate (percentage) in the tumor (about 20%). Collectively, these findings suggested that this orthotopic human colorectal tumor model in nude rats is useful to evaluate the clinical therapeutic efficacy of drugs or therapies for colorectal cancer, and that S-1 had a higher therapeutic effect on human colorectal tumor than UFT did.     

A prospective randomized evaluation of a compound of tegafur and uracil as an adjuvant chemotherapy for hepatocellular carcinoma treated with transcatheter arterial chemoembolization

A prospective randomized trial was conducted to evaluate the efficacy of long-term oral administration of low-dose tegafur combined with uracil as an adjuvant chemotherapy, following transcatheter arterial embolization (TAE) in 40 patients with hepatocellular carcinoma (HCC). Forty eligible patients were randomized into two groups: 20 with TAE plus UFT (a compound of tegafur 200 mg and uracil 448 mg per day) and 20 with TAE alone. A good necrosis rate or decrease in size of more than 70% of the original tumor mass was attained in 10 by TAE plus UFT arm and in 12 by TAE arm alone. As for the "responded" patients, there was no significant difference in the time from tumor response to tumor regrowth between the two groups. The appearance rate of ascites and/or encephalopathy in patients with chemotherapy was slightly higher than that in control patients. The median survival time was 22.7 months for TAE plus UFT arm and 28.2 months for TAE arm alone. There was no significant difference in the cumulative survival curves. In conclusion, these results indicated no substantial benefit for this chemotherapy regimen, as an adjuvant therapy for patients with HCC during repeated TAE.     

Evaluation of optimal measuring site and index by QDR4500A for postmenopausal bone loss]

Adjuvant therapy and microsurgery have allowed advances in surgical extirpation of lower extremity neoplasms. This retrospective study was designed to evaluate the microvascular transfer for lower extremity reconstruction in patients receiving pre- or post-operative irradiation and chemotherapy alone and in combination. Over a 5-year period, 24 free tissue transfers were performed in 22 patients undergoing surgical resection with adjuvant therapy for lower extremity neoplasms. There were 13 male and 9 female patients with an average age of 51 years. The latissimus dorsi muscle was most commonly transferred (N = 15). Eighteen tumors received pre- and three received postoperative radiotherapy. Two tumors received a combination of radiotherapy and brachytherapy. Pre- and/or postoperative chemotherapy was used in 14 patients. Twelve of these patients had both chemo- and radiation therapy. A total of six complications occurred, with no flap loss. Complications were evenly distributed among adjuvant regimens. All patients who underwent attempted limb salvage were able to ambulate postoperatively, except for 1 patients who had local recurrence. In conclusion, adjuvant therapy did not increase the complication rate for free tissue transfer in the lower extremity. Adjuvant therapy did not require alterations in the free tissue transfer and, similarly, free tissue transfer did not alter adjuvant therapy. We believe that free tissue transfer in complicated wounds allows for better wound healing with adjuvant therapy rather than local or primary wound closure alone.     

Resection margins, extrapleural nodal status, and cell type determine postoperative long-term survival in trimodality therapy of malignant pleural mesothelioma: results in 183 patients

OBJECTIVES: Our aim was to identify prognostic variables for long-term postoperative survival in trimodality management of malignant pleural mesothelioma. METHODS: From 1980 to 1997, 183 patients underwent extrapleural pneumonectomy followed by adjuvant chemotherapy and radiotherapy. RESULTS: Forty-three women and 140 men (age range 31-76 years) had a median follow-up of 13 months. The perioperative mortality rate was 3.8% (7 deaths) and the morbidity, 50%. Survival in the 176 remaining patients was 38% at 2 years and 15% at 5 years (median 19 months). Univariate analysis identified 3 prognostic variables associated with improved survival: epithelial cell type (52% 2-year survival, 21% 5-year survival, 26-month median survival; P =.0001), negative resection margins (44% at 2 years, 25% at 5 years, median 23 months; P =.02), and extrapleural nodes without metastases (42% at 2 years, 17% at 5 years, median 21 months; P =.004). Using the Cox proportional hazards, the relative risk of death was calculated for nonepithelial cell type (OR 3.0, CI 2.0-4.5; P <.0001), positive resection margins (OR 1.7, CI 1.2-2.6; P =.0082), and metastatic extrapleural nodes (OR 2.0, CI 1.3-3.2; P =.0026). Thirty-one patients with 3 positive variables had the best survival (68% 2-year survival, 46% 5-year survival, median 51 months; P =.013). A previously published staging system using these variables stratified survival (P <.05). CONCLUSIONS: (1) Multimodality therapy including extrapleural pneumonectomy is feasible in selected patients with malignant pleural mesotheliomas, (2) pre-resectional evaluation of extrapleural nodes may select patients for radical therapy, (3) microscopic resection margins affect long-term survival, highlighting the need for further investigation of locoregional control, and (4) patients with epithelial, margin-negative, extrapleural node-negative resection had extended survival.     

Sensitization of olfactory guanylyl cyclase to a specific imprinted odorant in coho salmon

PURPOSE: Local recurrence is a significant problem following primary surgery for advanced vulva carcinoma. The objectives of this study were to evaluate the impact of adjuvant vulvar radiation on local control in high risk patients and the impact of local recurrence on overall survival. METHODS AND MATERIALS: From 1980-1994, 62 patients with invasive vulva carcinoma and either positive or close (less 8 mm) margins of excision were retrospectively studied. Thirty-one patients were treated with adjuvant radiation therapy to the vulva and 31 patients were observed after surgery. Kaplan-Meier estimates and the Cox proportional hazard regression model were used to evaluate the effect of adjuvant radiation therapy on local recurrence and overall survival. Independent prognostic factors for local recurrence and survival were also assessed. RESULTS: Local recurrence occurred in 58% of observed patients and 16% in patients treated with adjuvant radiation therapy. Adjuvant radiation therapy significantly reduced local recurrence rates in both the close margin and positive margin groups (p = 0.036, p = 0.0048). On both univariate and multivariate analysis adjuvant radiation and margins of excision were significant prognostic predictors for local control. Significant determinants of actuarial survival included International Federation of Gynecologists and Obstetricians (FIGO) stage, percentage of pathologically positive inguinal nodes and margins of excision. The positive margin observed group had a significantly poorer actuarial 5 year survival than the other groups (p = 0.0016) and adjuvant radiation significantly improved survival for this group. The 2 year actuarial survival after developing local recurrence was 25%. Local recurrence was a significant predictor for death from vulva carcinoma (risk ratio 3.54). CONCLUSION: Local recurrence is a common occurrence in high risk patients. In this study adjuvant radiation therapy significantly reduced local recurrence rates and may improve overall survival in certain subgroups. As salvage rates after developing local recurrence are poor adjuvant vulvar radiation should be considered for patients at risk after primary surgery.     

Adjuvant 5-fluorouracil and leucovorin with or without interferon alfa-2a in colon carcinoma: National Surgical Adjuvant Breast and Bowel Project protocol C-05

BACKGROUND: National Surgical Adjuvant Breast and Bowel Project (NSABP) protocol C-03 showed a benefit from leucovorin (LV)-modulated 5-fluorouracil (5-FU) adjuvant therapy (5-FU + LV) in patients with Dukes' stage B or C carcinoma of the colon. Preclinical and clinical phase I/II data suggested that interferon alfa-2a (IFN) enhanced the efficacy of 5-FU therapy. Accordingly, in NSABP protocol C-05, the addition of recombinant IFN to 5-FU + LV adjuvant therapy was evaluated. METHODS: Data are presented for 2176 patients with Dukes' stage B or C cancer entered onto protocol C-05 during the period from October 1991 through February 1994. Individuals with an Eastern Cooperative Oncology Group performance status of 0-2 (ranges from fully active to ambulatory and capable of self-care but unable to work), a life expectancy of at least 10 years, and curative resection were stratified by sex, disease stage, and number of involved lymph nodes and were randomly assigned to receive either 5-FU + LV or 5-FU + LV + IFN; the mean time on the study as of June 30, 1997, was 54 months. All statistical tests were two-sided. RESULTS: There was no statistically significant difference in either disease-free survival (5-FU + LV, 69%; 5-FU + LV + IFN, 70%) or overall survival (5-FU + LV, 80%; 5-FU + LV + IFN, 81%) at 4 years of follow-up. Toxic effects of grade 3 or higher were observed in 61.8% of subjects in the group treated with 5-FU + LV and in 72.1% of subjects in the group treated with 5-FU + LV + IFN; fewer patients in the latter group completed protocol-mandated 5-FU + LV therapy than in the former group (77.1% versus 88.5%). CONCLUSION: The addition of IFN to 5-FU + LV adjuvant therapy confers no statistically significant benefit, but it does increase toxicity.     

Adjuvant cyclophosphamide, doxorubicin, vincristine, and prednisone chemotherapy after radiation therapy in stage I low-grade and intermediate-grade non-Hodgkin lymphoma. Results of a prospective randomized study

BACKGROUND: In a prospective randomized manner, this study evaluated the effect of adjuvant chemotherapy (cyclophosphamide, doxorubicin, vincristine, and prednisone; CHOP) in patients with Stage I non-Hodgkin lymphoma (NHL) who have achieved a complete response (CR) after radiation therapy (RT). METHODS: Forty-four patients with clinical or pathologic Stage I intermediate-grade or low-grade NHL were randomized to receive regional RT alone (median dose, 40 Gy) or regional RT followed by six cycles of CHOP chemotherapy. There were no differences in clinical and pathologic characteristics between the two treatment groups. RESULTS: The median follow-up was 7 years (range, 2-10 years). The actuarial relapse-free survival (RFS) rate for the RT plus CHOP group at 7 years was 83% compared with 47% (P < 0.03) for the RT-alone group. The overall survival (OS) for the two groups was 88% and 66%, respectively (P = 0.2). In patients with intermediate-grade NHL, the 7-year actuarial RFS for RT and CHOP was 86% compared with 20% for RT alone (P = 0.004). The corresponding actuarial survival rates were 92% and 47%, respectively (P = 0.08). In patients with low-grade histologic findings, the addition of adjuvant CHOP did not improve RFS (P = 0.6) or OS. All relapses in this study were at sites remote from the initially involved areas, and in 5 of 11 patients (45%), there were recurrences 5 years or longer after initial treatment. CONCLUSIONS: This study showed that adjuvant CHOP chemotherapy significantly improves RFS in patients with Stage I intermediate-grade NHL who achieve a CR after regional-field RT. The chemotherapeutic regimen favorably affected their probability of survival.     

A randomized trial of long term adjuvant tamoxifen plus postoperative radiation therapy versus radiation therapy alone for patients with early stage breast carcinoma treated with breast-conserving surgery. Stockholm Breast Cancer Study Group

BACKGROUND: The use of adjuvant tamoxifen to treat postmenopausal breast carcinoma patients as an adjunct to primary surgery is well established. The current study reports the long term results for a low risk stratum in a randomized trial of adjuvant tamoxifen. The main focus of this analysis was to determine whether tamoxifen would result in a reduced local failure rate for lymph node negative, postmenopausal patients treated with breast-conserving surgery and postoperative radiotherapy. METHODS: The study population included 432 lymph node negative, postmenopausal patients with invasive breast carcinoma (classified as T1-T2) who underwent breast-conserving surgery followed by radiotherapy in Stockholm during the period 1976-1990. The patients constituted a separate stratum of the Stockholm Adjuvant Tamoxifen Trial, which included a total of 2729 patients. Of 432 patients, 213 received 40 mg of tamoxifen daily for either 2 or 5 years. The median follow-up time was 8 years (range, 5-19 years). RESULTS: At 10 years, the overall survival was 90% for the tamoxifen group and 88% for the control group. The event free survival at 10 years was 80% for the tamoxifen group and 70% for the control group (P=0.03). Tamoxifen reduced the overall rate of ipsilateral (hazard ratio=0.4, 95% confidence interval [CI]=0.2-0.9, P=0.02) and contralateral breast tumor recurrences (hazard ratio=0.4, 95% CI=0.1-1.1, P=0.06). Trends toward a reduced number of distant metastases (hazard ratio=0.6, 95% CI=0.3-1.2, P=0.1) and deaths due to breast carcinoma (hazard ratio=0.5, 95% CI=0.2-1.2, P=0.1) also were observed. CONCLUSIONS. The addition of tamoxifen to radiotherapy for postmenopausal, lymph node negative breast carcinoma patients treated with breast-conserving surgery resulted in a reduced rate of ipsilateral and contralateral breast tumor recurrences. The avoidance of salvage mastectomies, reexcisions, and new contralateral malignancies justifies the use of tamoxifen even in the treatment of patients with a 10-year survival rate of 90%.     

Randomised trial of interferon alpha-2a as adjuvant therapy in resected primary melanoma thicker than 1.5 mm without clinically detectable node metastases. French Cooperative Group on Melanoma

BACKGROUND: Owing to the limited efficacy of therapy on melanoma at the stage of distant metastases, a well-tolerated adjuvant therapy is needed for patients with high-risk primary melanoma. Our hypothesis was that an adjuvant treatment with low doses of interferon alpha could be effective in patients with localised melanoma. METHODS: After resection of a primary cutaneous melanoma thicker than 1.5 mm, patients without clinically detectable node metastases were randomly assigned to receive either 3x10(6) IU interferon alpha-2a, three-times weekly for 18 months, or no treatment. The primary endpoint was the relapse-free interval. FINDINGS: 499 patients were enrolled, of whom 489 were eligible. When used as part of a sequential procedure, interferon alpha-2a was of significant benefit for relapse-free interval (p=0.038). A long-term analysis, after a median follow-up of 5 years, showed a significant extension of relapse-free interval (p=0.035) and a clear trend towards an increase in overall survival (p=0.059) in interferon alpha-2a-treated patients compared with controls. There were 100 relapses and 59 deaths among the 244 interferon alpha-2a-treated patients compared with 119 relapses and 76 deaths among the 245 controls. The estimated 3-year-relapse rates were 32% in the interferon alpha-2a group and 44% in controls; the 3-year death rates were 15% and 21%, respectively. Only 10% of patients experienced WHO grade 3 or 4 adverse events. Treatment was compatible with normal daily life. INTERPRETATION: Adjuvant therapy of high-risk melanoma with low doses of interferon alpha-2a for 18 months is safe and is beneficial when started before clinically detectable node metastases develop.     

Combination chemotherapy with 5-FU and CDDP or CDDP analog for head and neck cancer

Combination chemotherapy with CDDP and 5-FU is one of the effective regimens for head and neck cancer. We studied the difference in the effects and adverse effects between two kinds of schedules of CDDP administration for CDDP-5-FU combination chemotherapy. For 13 patients, CDDP was administered on 5 consecutive days from day 1 to day 5 at a daily dose of 16 mg/m2 (Regimen A). For 14 patients CDDP was administered 80 mg on day 1 (Regimen B). 5-FU was administered 700 mg/m2/ day as a continuous drip infusion for 120 hours from day 1 to day 5. For regimen A, the response rate was 77%; for regimen B, it was 64%. The pattern of adverse effects showed a difference. Regimen B was more toxic for renal function than regimen A. But regimen A showed toxicity for bone marrow function. Acute phase nausea and vomit appeared more frequently in regimen B. The difference in the adverse effect pattern, which depends on the schedule of CDDP administration, seems important in order to apply this regimen for head and neck cancer patients safely. The schedule of CDDP administration should be changes depending on the renal and bone marrow function of patients. In order to evaluate the efficacy of UFT as adjuvant chemotherapy, UFT was administered p.o. to patients with maxillary sinus carcinoma for more than one year after definitive treatment with surgery or radiotherapy. Fifteen patients with UFT adjuvant chemotherapy showed significantly better survival rates than patients without adjuvant chemotherapy. We also studied adjuvant chemotherapy with CBDCA and FT for patients with advanced head and neck cancer. Administration with UFT (600 mg/day) from day 1 to day 14 with CBDCA 350 mg/m2 at day 7 was repeated more than twice. This regimen showed low toxicity and better survival for nasopharyngeal cancer patients. More clinical trials with this regimen for adjuvant chemotherapy are needed.     

Adjuvant combination chemotherapy (AMF) following radical resection of carcinoma of the pancreas and papilla of Vater--results of a controlled, prospective, randomised multicentre study

Between 1984 and 1987, 61 radically resected patients with carcinoma of the pancreas (n = 47) or the papilla of Vater (n = 14) were randomised either into postoperative adjuvant combination chemotherapy (AMF); 5-fluorouracil 500 mg/m2, doxorubicin 40 mg/m2, mitomycin C 6 mg/m2 (n = 30) once every 3 weeks for six cycles, or into a control group (no adjuvant chemotherapy) (n = 31). The median survival in the treatment group was 23 months compared with 11 months (P = 0.02, median test) in the control group, dependent on a survival benefit in the treatment group during the initial 2 years (P = 0.04 generalised Wilcoxon). The long-term prognosis was the same with an identical survival after 2 years (P = 0.10, power = 0.83). The observed 1, 2, 3 and 5-year survivals in the treatment group were 70, 43, 27 and 4% compared with 45, 32, 30 and 8 in the control group. 1 patient succumbed to sepsis probably attributable to chemotherapy. Cardiotoxicity and nephrotoxicity were recorded in 2 patients. These results suggest that adjuvant chemotherapy does postpone the incidence of recurrence in the first 2 years following radical surgery but increased cure rate was not observed.