Skin lesions in malignancy. Case 2. Skin metastases from prostate adenocarcinoma.
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Adenocarcinoma↗
Biomedical subjects
R W Carey
Publications and source records attributed to R W Carey.
Stage III thymoma: pattern of failure after surgery and postoperative radiotherapy and its implication for future study.
PURPOSE: With the conventional approach of surgery and postoperative radiotherapy for patients with Masaoka Stage III thymoma, progress has been slow for an improvement in the long-term survival rate over the past 20 years. The objective of this study was to evaluate the pattern of failure and survival after surgery and postoperative radiotherapy in Stage III thymoma and search for a new direction for better therapy outcome. METHODS AND MATERIALS: Between 1975 and 1993, 111 patients with thymoma were treated at Massachusetts General Hospital. Of these, 32 patients were determined to have Masaoka Stage III thymoma. The initial treatment included surgery for clinically resectable disease in 25 patients and preoperative therapy for unresectable disease in 7 patients. Surgical procedure consisted of thymectomy plus resection of involved tissues. For postoperative radiotherapy (n = 23), radiation dose consisted of 45-50 Gy for close resection margins, 54 Gy for microscopically positive resection margins, and 60 Gy for grossly positive margins administered in 1.8 to 2.0 Gy of daily dose fractions, 5 fractions a week, over a period of 5 to 6.6 weeks. In preoperative radiotherapy, a dose of 40 Gy was administered in 2.0 Gy of daily dose fractions, 5 days a week. For patients with large tumor requiring more than 30% of total lung volume included in the target volume (n = 3), a preoperative radiation dose of 30 Gy was administered and an additional dose of 24-30 Gy was given to the tumor bed region after surgery for positive resection margins. RESULTS: Patients with Stage III thymoma accounted for 29% (32/111 patients) of all patients. The median age was 57 years with a range from 27 to 81 years; gender ratio was 10:22 for male to female. The median follow-up time was 6 years. Histologic subtypes included well-differentiated thymic carcinoma in 19 (59%), high-grade carcinoma in 6 (19%), organoid thymoma in 4 (13%), and cortical thymoma in 3 (9%) according to the Marino and Müller-Hermelink classification. The overall survival rates were 71% and 54% at 5 and 10 years, respectively. Ten of the 25 patients who were subjected to surgery as initial treatment were found to have incomplete resection by histopathologic evaluation. The 5- and 10-year survival rates were 86% and 69% for patients (n = 15) with clear resection margins as compared with 28% and 14% for those (n = 10) with incomplete resection margins even after postoperative therapy, p = 0.002. Survival rates at 5 and 10 years were 100% and 67% for those with unresectable disease treated with preoperative radiation (n = 6) and subsequent surgery (n = 3). Recurrence was noted in 12 of 32 patients and 11 of these died of recurrent thymoma. Recurrences at pleura and tumor bed accounted for 77% of all relapses, and all pleural recurrences were observed among the patients who were treated with surgery initially. CONCLUSION: Incomplete resection leads to poor results even with postoperative radiotherapy or chemoradiotherapy in Stage III thymoma. Pleural recurrence is also observed more often among patients treated with surgery first. These findings suggest that preoperative radiotherapy or chemoradiotherapy may result in an increase in survival by improving the rate of complete resection and reducing local and pleural recurrences.
Adult↗
Phase I study to determine the maximum-tolerated dose of radiation in standard daily and hyperfractionated-accelerated twice-daily radiation schedules with concurrent chemotherapy for limited-stage small-cell lung cancer.
PURPOSE: An improvement in radiation dose schedule is necessary to increase local tumor control and survival in limited-stage small-cell lung cancer. The goal of this study was to determine the maximum-tolerated dose (MTD) of radiation (RT) in both standard daily and hyperfractionated-accelerated (HA) twice-daily RT schedules in concurrent chemoradiation. METHODS: The study design consisted of a sequential dose escalation in both daily and HA twice-daily RT regimens. RT dose to the initial volume was kept at 40 to 40.5 Gy, while it was gradually increased to the boost volume by adding a 7% to 11 % increment of total dose to subsequent cohorts. The MTD was defined as the radiation dose level at one cohort below that which resulted in more than 33% of patients experiencing grade > or = 4 acute esophagitis and/or grade > or = 3 pulmonary toxicity. The study plan included nine cohorts, five on HA twice-daily and four on daily regimens for the dose escalation. Chemotherapy consisted of three cycles of cisplatin 33 mg/m2/d on days 1 to 3 over 30 minutes, cyclophosphamide 500 mg/m2 on day 1 intravenously (IV) over 1 hour, and etoposide 80 mg/m2/d on days 1 to 3 over 1 hour every 3 weeks (PCE) and two cycles of PE. RT was started at the initiation of the fourth cycle of chemotherapy. RESULTS: Fifty patients were enrolled onto the study. The median age was 60 years (range, 38-79), sex ratio 2.3:1 for male to female, weight loss less than 5% in 73%, and performance score 0 to 1 in 94% and 2 in 6% of patients. In HA twice-daily RT, grade > or = 4 acute esophagitis was noted in two of five (40%), two of seven (29%), four of six (67%), and five of six patients (86%) at 50 (1.25 Gy twice daily), 45, 50, and 55.5 Gy in 1.5 Gy twice daily, 5 d/wk, respectively. Grade > or = 3 pulmonary toxicity was not seen in any of these 24 patients. Therefore, the MTD for HA twice-daily RT was judged to be 45 Gy in 30 fractions over 3 weeks. In daily RT, grade > or = 4 acute esophagitis was noted in zero of four, zero of four, one of five (20%), and two of six patients (33%) at 56, 60, 66, and 70 Gy on a schedule of 2 Gy per fraction per day, five fractions per week. Grade > or = 3 pneumonitis was not observed in any of the 19 patients. Thus, the MTD for daily RT was judged to be at least 70 Gy in 35 fractions over 7 weeks. Grade 4 granulocytopenia and thrombocytopenia were observed in 53% and 6% of patients, respectively, during the first three cycles of PCE. During chemotherapy cycles 4 to 5, grade 4 granulocytopenia and thrombocytopenia were noted in 43% and 29% of patients at 45 Gy in 30 fractions over 3 weeks (MTD) by HA twice-daily RT and 50% and 17% at 70 Gy in 35 fractions over 7 weeks (MTD) by daily RT, respectively. The overall tumor response consisted of complete remission (CR) in 51% (24 of 47), partial remission (PR) in 38% (1 8 of 47), and stable disease in 2% (one of 47). The median survival time of all patients was 24.4 months and 2- and 3-year survival rates were 53% and 28%, respectively. With regard to the different radiation schedules, 2- and 3-year survival rates were 52% and 25% for the HA twice-daily and 54% and 35% for the daily RT cohorts. CONCLUSION: The MTD of HA twice-daily RT was determined to be 45 Gy in 30 fractions over 3 weeks, while it was judged to be at least 70 Gy in 35 fractions over 7 weeks for daily RT. A phase III randomized trial to compare standard daily RT with HA twice-daily RT at their MTD for local tumor control and survival would be a sensible research in searching for a more effective RT dose-schedule than those that are being used currently.
Adult↗
Endoscopic ultrasound staging criteria for esophageal cancer.
BACKGROUND: Malignant esophageal masses can be staged with endoscopic ultrasound (EUS) using the TNM staging classification. Several criteria for differentiating between intraesophageal (T1-2) and extraesophageal (T3-4) masses have been described, but highly accurate staging remains difficult. METHODS: This is a blinded evaluation of four specific EUS criteria in 24 patients with esophageal malignancy who underwent esophageal resection after neoadjuvant chemotherapy. Radial EUS was used to evaluate the first 12 patients and curved linear EUS was used in the second half of the group. Using the histology of the resected specimens, the sensitivity, specificity, and accuracy of the EUS criteria after chemotherapy were determined for predicting intraesophageal or extraesophageal invasion. RESULTS: There was no difference in the accuracy rates with radial or linear EUS. Two ultrasound criteria, muscularis disruption and irregular mass border, were found to have low accuracy rates (44% and 50%). The maximal thickness (overall or extraesophageal) of the esophageal mass was found to be highly accurate (79% and 87%) in predicting intraesophageal or extraesophageal extension. pT3-4 masses had a thickness of 16.0 +/- 2 mm, significantly greater than pT1-2 masses, 8.2 +/- 1 mm (p < .01). Using receiver operator characteristics (ROC) curve analysis, mass thickness was found to be more accurate (91% and 94%) than a subjective assessment of staging (73%) (p < .07). CONCLUSIONS: The EUS measurement of a malignant esophageal mass maximal thickness can accurately predict extraesophageal extension.
Adenocarcinoma↗
Induction therapy for esophageal cancer with paclitaxel and hyperfractionated radiotherapy: a phase I and II study.
OBJECTIVE: Induction chemoradiotherapy followed by surgery may improve survival rates among patients with esophageal carcinoma. We designed a novel intense induction regimen with paclitaxel and high-dose hyperfractionated radiotherapy to maximize complete response rates. METHODS: Forty patients with esophageal cancer were treated in a phase I and II trial of induction chemotherapy (cisplatin, 5-fluorouracil, and paclitaxel) at three dosage levels (75, 125, and 100 mg/m2) and concurrent hyperfractionated radiotherapy (45 Gy to the mediastinum, 58.5 Gy to the tumor). The mean age was 62 years, and 32 patients (80%) had adenocarcinoma. Twenty-eight of 40 (70%) patients had locally advanced tumors (T3, or stage IIB or greater). RESULTS: The average hospitalization for induction treatment was 17 days. Toxicity was substantial, with esophagitis necessitating nutritional support the most common complication. The maximum tolerated dose of paclitaxel was 100 mg/m2. Two patients died during induction treatment. Thirty-six patients (90%) underwent resection. The median length of stay was 10 days, and two patients died after the operation. Fourteen of 36 patients (39%) had a pathologic complete response. Patients who received all prescribed chemotherapy had a higher pathologic complete response rate (50%) than did patients who required dose reduction (17%; p = 0.076). The 2-year survival rate was 61% (95% CI 35% to 86%) with a median follow-up of 11.9 months. CONCLUSIONS: Paclitaxel at a dose of 100 mg/m2 appears to have acceptable toxicity. The high pathologic complete response rate in this regimen is encouraging, but it is associated with substantial toxicity. The toxicity of this regimen is not acceptable and will require substantial reduction in the radiation component. Survival data are too short-term to confirm enhanced survival.
Adenocarcinoma↗
Randomized trial of chemotherapy and radiation therapy with or without warfarin for limited-stage small-cell lung cancer: a Cancer and Leukemia Group B study.
PURPOSE: Studies by the Veterans Administration Cooperative Studies Program and Cancer and Leukemia Group B (CALGB) suggested that the addition of warfarin to chemotherapy might enhance response and/or survival in small-cell lung cancer (SCLC). This randomized study evaluated the effect of warfarin with chemotherapy and radiation therapy in limited-stage SCLC. PATIENTS AND METHODS: Patients were randomized to receive warfarin or no warfarin. All patients received three cycles of doxorubicin, cyclophosphamide, and etoposide (ACE). Cycles 4 and 5 (cisplatin, cyclophosphamide, and etoposide [PCE]) were given concurrently with radiation therapy. Three cycles of ACE were given after chemoradiation therapy, but were discontinued due to a high rate of pulmonary toxicity. RESULTS: There were no significant differences in response rates, survival, failure-free survival, disease-free survival, or patterns of relapse between the warfarin-treated and control groups. In patients treated according to the initial design, an increase in failure-free survival seen with warfarin treatment approached significance (P = .07). Preamendment results, while not significant, did not have superimposable treatment survival curves. A landmark analysis at 8 months showed a median survival time after the landmark for complete responders of 33 months with warfarin treatment compared with < or = 13.75 months for complete or partial responders not treated with warfarin (P = .05). Differences between the complete responders in this preamendment population were not significant (P = .103). CONCLUSION: Warfarin does not appear to improve outcome significantly in limited-stage SCLC. However, the differences in some variables between populations before the protocol amendment correspond to the favorable effects of anticoagulants observed in previous studies.
Adult↗
Potential impact on survival of improved tumor downstaging and resection rate by preoperative twice-daily radiation and concurrent chemotherapy in stage IIIA non-small-cell lung cancer.
PURPOSE: The main objectives of this study were (a) to ascertain the feasibility and toxicity of preoperative twice-daily radiation therapy and concurrent chemotherapy, surgery, and postoperative therapy in stage IIIA (N2) non-small-cell lung cancer (NSCLC), and (b) to evaluate tumor response, resection rate, pathologic tumor downstaging, and survival. METHODS: Eligibility included biopsy-proven N2 lesion (stage IIIA) by mediastinoscopy, Karnofsky performance score > or = 70, and weight loss less than 5% in the 3 months before diagnosis. The treatment program consisted of two courses of preoperative cisplatin, vinblastine, and fluorouracil (5-FU); 42 Gy concurrent radiation at 1.5 Gy per fraction in two fractions per day; surgery on day 57; and one more course of postoperative chemotherapy and 12 to 18 Gy of concurrent twice-daily radiation. RESULTS: Forty-two patients with stage IIIA (N2) NSCLC (27 men and 15 women, age 38 to 77 years) were enrolled onto this prospective study. Forty of 42 patients tolerated the intended dose (42 Gy) of preoperative radiation and 37 of 39 resected patients received prescribed postoperative radiation. The intended dose of chemotherapy was given in 100%, 70%, and 60% of patients for the first, second, and third courses of chemotherapy. Marked dysphagia that required intravenous hydration was noted in 14% of patients (six of 42). Myelotoxicities included grade > or = 3 granulocytopenia in 23% and thrombocytopenia in 6% of 113 chemotherapy courses. Febrile neutropenia that required hospital admission was noted in 9% of 113 chemotherapy courses. Surgical resection was performed in 93% of patients. Treatment-related mortality was noted in 7% of patients. The overall survival rates by the Kaplan-Meier method were 66%, 37%, and 37% at 2,3, and 5 years, respectively, with a median follow-up time of 48 months. Pathologic examination of the surgical specimen showed a downward shift in tumor extent from stage IIIA (N2) to stage II (N1) in 33%, to stage I (NO) in 24% (10 of 42), and to stage 0 (TONO) in 9.5%, for a total of 67%. The degree of tumor downstaging was also translated into a survival benefit: 5-year survival rates from the time of surgery were 79%, 42%, and 18% for postoperative tumor stages 0 and I, II, and III, respectively (P = .04). CONCLUSION: Concurrent chemoradiotherapy using twice-daily radiation is an effective induction regimen that resulted in 67% tumor downstaging, and an encouraging 37% 5-year survival rate. The degree of tumor downstaging may be a useful intermediate end point for survival benefit in stage IIIA (N2) NSCLC.
Adult↗
Ifosfamide/carboplatin/etoposide/paclitaxel in advanced lung cancer: update and preliminary survival analysis.
The primary objective of this study was to define the maximum tolerated dose and toxicity profile of paclitaxel (Taxol; Bristol-Myers Squibb Company, Princeton, NJ), given as a 24-hour infusion, in conjunction with ifosfamide/carboplatin/etoposide (ICE) chemotherapy in patients with advanced lung cancer. Paclitaxel was escalated from 75 to 225 mg/m2 in 25-mg/m2 increments. All patients received granulocyte colony-stimulating factor 5 microg/kg/d from day 4 until the neutrophil count was > or = 10,000/microL. The study population consisted of 41 patients with a median age of 60 years and a median follow-up of 20.7 months. Stage distribution included 5% stage IIIA, 46% stage IIIB, and 49% stage IV. Histology consisted of 61% adenocarcinoma, 12% squamous cell carcinoma, 10% large cell carcinoma, 15% small cell carcinoma, and 2% mixed. The predominant toxicity was hematologic; 63% of patients experienced grade 4 neutropenia and 49% developed grade 4 thrombocytopenia. Fever and neutropenia occurred in 34% of patients. Hematologic toxicity was, in all cases, short-term and reversible and was not dose related. With few exceptions, nonhematologic toxicity was not clinically important. Among 39 patients evaluable for response, 36% achieved a remission (8% complete, 28% partial, 41% had stable disease, and 23% experienced disease progression). Among 33 patients with non-small cell lung cancer, the response rate was 27% (one complete response, eight partial responses, 15 had stable disease, and nine had progressive disease). Among six patients with small cell carcinoma, the response rate was 83% (two complete responses, three partial responses, and one had stable disease). The median survival of all 41 patients was 13.6 months. Survival was almost identical between stage IIIA and stage IV subsets. We conclude that it is possible to safely administer full-dose single-agent paclitaxel with granulocyte colony-stimulating factor support in conjunction with full-dose ifosfamide/carboplatin/etoposide chemotherapy. While response rates observed were not particularly notable, median survival is considerably longer than that usually achieved with combination chemotherapy in advanced lung cancer.
Adult↗
Postsurgical adjuvant chemotherapy of stage II breast carcinoma with or without crossover to a non-cross-resistant regimen: a Cancer and Leukemia Group B study.
PURPOSE: To compare two cyclophosphamide, methotrexate, fluorouracil, vincristine, and prednisone (CMFVP) regimens with a doxorubicin-based regimen--vinblastine, doxorubicin, thiotepa, and Halotestin (Upjohn, Kalamazoo, MI) (VATH)--in patients with stage II node-positive breast carcinoma. METHODS: Nine hundred forty-five women were treated with a 6-week induction course of CMFVP. They were then randomized to receive one of two consolidation CMFVP regimens: 6-week courses or 2-week courses. Following completion of CMFVP consolidation, patients were again randomized to either continue the CMFVP regimen or to receive six escalating doses of VATH. RESULTS: Among all patients, with a median follow-up time of 11.5 years, there is no statistically significant difference in disease-free survival (DFS) between the two consolidation CMFVP regimens. VATH intensification treatment is statistically significantly superior to CMFVP in terms of DFS (P = .0040). For patients with one to three involved nodes, there is currently no significant difference between VATH and CMFVP; however, among those with four or more positive lymph nodes, there is a significant difference in favor of VATH (P = .0037). There is also improved overall survival with VATH (P = .043; median, > 14 years v 10 years). This difference is also statistically significant in patients with four or more involved lymph nodes, among postmenopausal patients, and among postmenopausal estrogen receptor-positive patients. CONCLUSION: Chemotherapy with crossover to escalating doses of VATH following CMFVP was well tolerated and effective. Inauguration of VATH as a treatment intensification at the eighth month produced a major increase in relapse-free and overall survival. The observation that sensitivity to VATH is retained so long after mastectomy raises questions about the proper duration of adjuvant chemotherapy and lends support to further investigation of cross-over designs in future trials to postoperative adjuvant chemotherapy regimens.
Adult↗
Non-Hodgkin's lymphoma presenting with biliary tract obstruction. A discussion of seven patients and a review of the literature.
BACKGROUND: Biliary tract obstruction is a rare manifestation of non-Hodgkin's lymphoma (NHL). Because of the small numbers of patients studied, management of this condition has been inconsistent. Most patients have been treated with biliary diversion, and doxorubicin frequently has been withheld from initial therapy. METHODS: Seven patients with NHL presenting with malignant biliary tract obstruction were identified at the Massachusetts General Hospital. Relevant clinical characteristics, laboratory values, treatment, and outcome are reported for all patients. Thirty-eight additional patients were identified through a MEDLINE search; and the management and results of the patients reported here are discussed with reference to those patients. RESULTS: Biliary tract obstruction was the presenting symptom in 0.8% of the patients with NHL. Bilirubin values at presentation ranged from 5.0-23.2 mg/dl. One patient had localized pancreatic lymphoma. Four of the seven patients had advanced-stage disease. The tumor was intermediate or high grade in five patients. Four patients underwent placement of a biliary stent or drainage catheter. Six patients received combination chemotherapy without doxorubicin in the initial cycle. Hyperbilirubinemia resolved in all patients within 3 months, regardless of use of a stent. Six patients responded to chemotherapy and one patient had progressive disease. Two of the six responders died, one with relapsed lymphoma. CONCLUSIONS: NHL presenting with biliary tract obstruction can be effectively treated with chemotherapy, with or without a procedure for biliary diversion. The use of doxorubicin in the presence of hyperbilirubinemia secondary to biliary tract obstruction remains controversial, and its omission from the initial cycles of chemotherapy for NHL may not influence outcome.
Adult↗
A phase I study of ifosfamide/carboplatin/etoposide/paclitaxel in advanced lung cancer.
A phase I study was conducted to define the maximally tolerated dose and toxicity profile of the ifosfamide/carboplatin/etoposide/paclitaxel (Taxol; Bristol-Myers Squibb Company, Princeton, NJ) (ICE-T) regimen in advanced lung cancer. This chemotherapy program uses paclitaxel given as a 24-hour continuous infusion in conjunction with full-dose ICE chemotherapy with growth factor support. The dosage of paclitaxel was escalated from 75 to 225 mg/m2. Thirty-four patients have been accrued to date onto this study. Because hematologic dose-limiting toxicity was defined in terms of neutropenia and/or thrombocytopenia exceeding 7 days' duration, no patient demonstrated what was defined by the protocol as dose-limiting toxicity. Nonetheless, substantial hematologic toxicity was observed. Overall, 26% had fever and neutropenia, 56% had grade 4 neutropenia, and 26% had grade 4 thrombocytopenia. In all cases, hematologic toxicity was short term and reversible. While grade 3 and 4 myelosuppression was frequently observed, it was not dose related (in terms of paclitaxel dosage). Nonhematologic toxicity also was not dose related and, with only a few exceptions, was not clinically significant. Among 27 patients evaluable for response, 41% achieved an objective response, including 15% with a complete response. All of five patients with small cell lung cancer responded (including two with a complete response). Among 22 patients with non-small cell lung cancer, 27% achieved an objective response (also including two with a complete response). The results of this study suggest that with growth factor support, it is possible to safely administer full-dose, single-agent paclitaxel in conjunction with full-dose ICE chemotherapy. We will soon be initiating a phase II study of the ICE-T regimen using paclitaxel at 225 mg/m2 as a 24-hour continuous infusion in advanced lung cancer. We will also conduct a phase I study of ICE-T, with paclitaxel administered as a 3-hour continuous infusion.
Adult↗
Evolution of treatment strategies for adenocarcinoma of the esophagus and gastroesophageal junction.
Between 1980 and 1988, 91 patients with adenocarcinoma of the esophagus were treated by surgical resection and selective postoperative therapy. Operative mortality was 2%. Pathologic stage was I in 4, II in 26, and III in 61. Actuarial 2- and 5-year survival was 24% and 8%. From 1987 to 1989, 16 patients with adenocarcinoma of the esophagus were treated with two cycles of 5-fluorouracil and cisplatin followed by surgical resection. There was 1 complete response (6%), 5 partial responses (31%), and 10 with no response (63%). Twelve patients had resection. Pathologic stage was I in 1, II in 4, and III in 8. There was one chemotherapy-related death and one surgical death. Actuarial 4-year survival is 42%. From 1990 to 1993, 22 patients with adenocarcinoma of the esophagus were treated with two cycles of etoposide, doxorubicin, and cisplatin followed by surgical resection. There was 1 complete response (5%), 11 partial responses (50%), and 10 with no response (45%). Eighteen patients had resection. Pathologic stage was 0 in 1, II in 8, and III in 9. There were no treatment-related deaths. The actuarial 2-year survival is 58%. Conclusions are necessarily limited because the patients were not treated in a randomized fashion. These preliminary results with preoperative chemotherapy appear improved (p = 0.04 and p = 0.004, respectively) as compared with results from 1980 to 1988 without preoperative chemotherapy.
Adenocarcinoma↗
Recombinant human erythropoietin therapy for anemic cancer patients on combination chemotherapy.
BACKGROUND: Patients with advanced cancer frequently experience clinically significant anemia, which is often exacerbated by myelosuppressive chemotherapy. Consistent with the anemia of chronic disease, studies have documented serum erythropoietin levels that are inappropriately low for the degree of anemia in cancer patients. Myelosuppressive chemotherapy impairs erythropoiesis, which may not fully recover between treatment cycles. Recombinant human erythropoietin (rHuEPO) has been used safely and effectively to treat anemia in AIDS patients receiving zidovudine (AZT) and in patients with chronic renal failure. PURPOSE: This study was designed to evaluate the clinical role of rHuEPO in reducing symptomatic anemia in patients with advanced cancer who were receiving myelosuppressive chemotherapy (excluding cisplatin). METHODS: We studied 153 anemic cancer patients receiving cyclic combination chemotherapy in a prospective multicenter, double-blind, placebo-controlled trial. The patients were randomly assigned to receive either rHuEPO (150 U/kg) or placebo subcutaneously three times a week for a maximum of 12 weeks or until the hematocrit level increased to 38%-40%. If the hematocrit reached this target level before 12 weeks, the rHuEPO dose could be reduced to maintain the hematocrit at that level for the duration of the study. Response to rHuEPO therapy was assessed by measuring changes in hematocrit level, transfusion requirements, and quality of life. Quality-of-life assessment was based on patients' responses to questionnaires before and after the courses of therapy. RESULTS: The increase in hematocrit in the rHuEPO-treated group compared with hematocrit in the placebo-treated group was statistically significant (P = .0001) as measured by percentage point of change from baseline to final evaluation, by an increase in hematocrit level of six percentage points or more unrelated to transfusion, and by a rise in hematocrit level to 38% or more unrelated to transfusion. There was a trend toward the reduction in mean units of blood transfused per patient during months 2 and 3 of therapy combined in rHuEPO-treated patients compared with placebo-treated patients (0.91 U versus 1.65 U; P = .056). In addition, rHuEPO-treated patients experienced a statistically significant improvement in energy level and ability to perform daily activities (P < or = .05). The two treatment groups showed no statistically significant differences in toxic effects except for increased incidence of diaphoresis (P < .05) and diarrhea (P = .05) in the rHuEPO-treated group. CONCLUSIONS: We conclude that rHuEPO is safe and effective for reversing anemia related to advanced cancer or to chemotherapy for cancer.
Adult↗
Obturator neuropathy after laparoscopic pelvic lymphadenectomy.
A case of obturator nerve injury with delayed manifestation following laparoscopic pelvic lymphadenectomy is presented. While the incidence of obturator nerve injury does not appear to differ between open surgical and laparoscopic approaches, the laparoscopic approach demands unequivocal visualization of the nerve when utilizing electrocautery because of the risk of nerve injury from thermal conduction through apposed tissues.
Humans↗
Long-term follow-up of neoadjuvant chemotherapy with 5-fluorouracil and cisplatin with surgical resection and possible postoperative radiotherapy and/or chemotherapy in squamous cell carcinoma of the esophagus.
Seventy patients with local squamous cell carcinoma of the esophagus were treated between 1981 and 1990 with preoperative chemotherapy, surgical resection, and possible postoperative radiation therapy and/or chemotherapy. Chemotherapy included two cycles of 5-fluorouracil (1000 mg/m2) by continuous intravenous infusion on days 1-4 and cisplatin (100 mg/m2) on day 4. Complete clinical response (CCR) was achieved in 28 (41%) patients, partial clinical response (PCR) in 17 (25%), and no response in 23 (34%). Fifty-five (81%) patients were resected, 6 (9%) were explored, and 7 (10%) were unable to have surgery. Microscopic analysis of 55 resected patients showed 50 (91%) with active tumor, 1 (2%) with necrotic tumor, and 4 (7%) with a pathological complete response to chemotherapy. Twenty-six of the 55 resected patients (47%) had no gross evidence of disease at the time of surgical inspection. Median overall survival was 21.86 months (range 2-107 months) for all patients and 26.71 months (range 2-107 months) for resected patients. Actuarial 5-year survival rate was 31% for all patients and 39% for resected patients. Prolonged survival correlates with complete clinical response to chemotherapy, low pathological stage of disease, and successful resection of the lesion.
Adult↗
Effects of treatment with 5-azacytidine on the in vivo and in vitro hematopoiesis in patients with myelodysplastic syndromes.
The myelodysplastic syndrome (MDS) comprises a group of clonal hematopoietic disorders derived from an abnormality affecting a multipotent hematopoietic stem cell. Despite trials testing numerous agents in patients with MDS, no single drug has yet emerged as the accepted standard of treatment. Observation and supportive care with blood products and antibiotics, when necessary, continue to be the mainstays of therapy. We administered 5-azacytidine, a cell-cycle specific ring analog of the pyrimidine nucleoside cytosine, as a continuous intravenous infusion, 75 mg/m2 per day for 7 days every 4 weeks. Patients had refractory anemia with excess blasts (RAEB) or refractory anemia with excess blasts in transformation (RAEB-T). Responses were seen in 21 (49%) of 43 evaluable patients: five (12%) in complete remission (CR, complete normalization of bone marrow and peripheral blood counts); 11 (25%) in partial remission (PR, > or = 50% restoration of the deficit from normal of all three peripheral blood cell lines, elimination of transfusion requirements, and a decrease in percentage bone marrow blasts by > or = 50% from prestudy values); five (12%) improved (> or = 50% restoration in the deficit from normal of one or more peripheral blood cell lines and/or a > or = 50% decrease in transfusion requirements). A trilineage improvement (CR and PR) occurred in 37% of the patients. The median survival for all patients was 13.3 months and the median duration of remission for those with CR and PR was 14.7 months. Mild to moderate nausea and/or vomiting was the most common side effect (63%). Myelosuppression, either bone marrow hypoplasia or drug related cytopenias requiring a reduction in the dose of azacitidine, occurred in only 33% of the patients. Prior to treatment, bone marrow erythroid progenitor cells were assayed in vitro. Colonies derived from erythroid burst-forming units (BFU-e) were undetectable in one patient and reduced in two. The number of colonies derived from erythroid colony-forming units (CFU-e)) were also reduced in two of the three patients. In the two patients with detectable colony growth prior to treatment, colony number decreased by day 8 of the first cycle, followed by a subsequent increase. Continued treatment with azacitidine led to normalization of the number of CFU-e derived colonies as well as an increase in the number of BFU-e derived colonies. This improvement in erythroid colony number correlated with the spontaneous rise in hemoglobin levels and red cell transfusion independence.(ABSTRACT TRUNCATED AT 400 WORDS)
Aged↗
Phase II trial of ifosfamide/mesna and mitoxantrone in previously treated patients with non-Hodgkin's lymphoma: cancer and leukemia group B study 8753.
Ifosfamide (2.0 g/m2 intravenously/day x 3) with mesna (400 mg/m2 intravenously q 4 h daily x 3) was combined with mitoxantrone (14 mg/m2 intravenously x 1) and given on a 3 week schedule to patients with previously treated non-Hodgkin's lymphoma. In 45 eligible/evaluable patients, a 47% response rate (95% confidence interval: 32%, 62%) was achieved of which 25% were complete responses and 22% were partial responses. Median duration of remission was 10 months with 42% of patients in remission at 18 months. Hematologic toxicity (granulocytopenia) was the dose-limiting toxicity with severe or life-threatening granulocytopenia in 98% of patients at full protocol doses. Nausea/vomiting was seen in 73% of patients but was usually mild/moderate. Three patients had significant hematuria secondary to ifosfamide. Two patients had severe changes in the left ventricular ejection fraction (LVEF) secondary to mitoxantrone; and one patient had acute neurologic dysfunction secondary to ifosfamide. Ifosfamide/mesna can be safely combined with mitoxantrone at full doses in previously treated patients with non-Hodgkin's lymphoma. This combination should be considered for other trials in lymphoma.
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Neoadjuvant chemotherapy and radiotherapy followed by surgery in stage IIIA non-small-cell carcinoma of the lung: report of a Cancer and Leukemia Group B phase II study.
PURPOSE: This phase II trial was designed to evaluate the feasibility, toxicity, response rates, and survival for neoadjuvant chemotherapy and radiotherapy (RT) followed by surgical resection in newly diagnosed patients with surgically staged IIIA non-small-cell lung carcinoma (NSCLC). PATIENTS AND METHODS: Previously untreated patients with NSCLC underwent bronchoscopy, chest and abdominal computed tomography (CT), bone scan, and surgical staging of the mediastinum. Neoadjuvant treatment consisted of concurrent chemotherapy and RT. Patients then underwent surgical resection, which was followed in turn by additional chemotherapy and RT. Chemotherapy included cisplatin 100 mg/m2 on days 1 and 29, vinblastine 3 mg/m2 on days 1 and 3 and 29 and 31, and fluorouracil (5-FU) 30 mg/kg/d by infusion on days 1 to 3 and 29 to 31 (FVP). RT began on day 1 and included 3,000 cGy in 15 fractions. Surgery took place on day 55, and one more cycle of chemotherapy and an additional 3,000 cGy of RT began on day 85. RESULTS: Forty-one eligible patients (median follow-up, 53 months) were studied. N2 disease was present in 80%, whereas 20% had T3N0 or T3N1 lesions. Response to neoadjuvant chemotherapy and RT included no complete responses (CR), 21 (51%) partial responses (PR) or regressions, 19 (46%) stable disease (SD), and one (2%) progressive disease (PD). Thirty-one patients underwent surgery, and 25 were resected. In four of the 25 resection specimens, no viable tumor was present, whereas in three of the six unresectable patients, extensive biopsy results demonstrated only necrotic tumor. The maximum response achieved using all protocol treatment was 27 (66%) CRs, seven (17%) PRs or regression, six (15%) SDs, and one (2%) PD. Toxicity was substantial and primarily hematologic. There were six (15%) treatment-related deaths, which included three perioperative deaths and three chemotherapy-related toxicity deaths. The Kaplan-Meier curve indicated a 1-year survival of 58% and a median survival of 15.5 months. Nine patients (22%) remain disease-free. CONCLUSIONS: There was a reasonably high rate of PR associated with concurrent neoadjuvant chemotherapy and RT, and a high percentage of patients who ultimately were rendered completely disease-free. However, treatment-related morbidity and mortality was common. Median survival seemed to be only modestly improved beyond that achieved with less intensive means of treatment. However, a group has emerged of patients who enjoy prolonged disease-free survival and possible cure.
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