Phase II study on cisplatin and ifosfamide in recurrent high grade gliomas

27 patients with recurrent high grade glioma following surgery and radiation therapy were treated with 100 mg/m2 cisplatin and 6 g/m2 ifosfamide per cycle, administered on days 1-3 in 4 week cycles, for a maximum of six cycles. Toxicity was assessed after every cycle. Response was assessed following every second cycle, and a 50% decrease of the largest cross-sectional tumour area on contrast enhanced magnetic resonance imaging or computed tomography scan was considered a partial response (PR). A total of 95 cycles was administered; 26 patients were evaluable for response. In 5 patients (19%), a PR was obtained (median time to progression (TTP): 34 weeks). Stable disease was observed in 6 patients (23%, median TTP: 22 weeks). The most frequent toxicity was haematological: 37% of cycles were complicated by a grade 3 or 4 leucopenia. 1 patients died, probably as a consequence of increased cerebral oedema induced by the cisplatin hydration schedule. Determination of the cisplatin concentration in this patient showed a 10-fold increase in the tumour concentration as compared with that in normal brain tissue, demonstrating the absence of a blood-brain barrier in the tumour. In conclusion, generally this schedule was well tolerated, but it is of moderate activity for recurrent glioma.     

Treatment of advanced or recurrent endometrial carcinoma with single-agent carboplatin

Cisplatin and the combination of cisplatin, doxorubicin, and cyclophosphamide have documented activity in women with advanced or recurrent endometrial adenocarcinoma. However, response duration has been short and toxicity is substantial. To determine if similar activity could be obtained with less morbidity, we prospectively treated 33 patients with 360 mg/m2 carboplatin given intravenously every 28 days. Mean patient age was 69 years (range 40-86); all had a Zubrod functional status of 2 or less. Seventeen patients had advanced primary tumors, and 16 had recurrent disease. Prior treatment included surgical resection in 29 cases, hormonal agents in 7, and radiotherapy in 22. No patient had received prior chemotherapy. Mean treatment was 5.7 cycles. Nine of 27 patients (33%) with measurable disease had objective responses, including three complete and six partial responses. Nonresponders included 10 patients with stable disease and 8 whose disease progressed while on treatment. Median time to response was 3 months. Median progression-free survival for responders and nonresponders was 5 and 4 months, respectively. At analysis, 20 patients had died of disease, 7 were alive with disease, and 6 were clinically free of disease. Disease-free patients include 1 with a complete response and 5 who began treatment without measurable disease. Median follow-up for surviving patients was 18 months (range 4-32). Treatment toxic effects were minimal and largely limited to myelosuppression; 3 patients had grade 3 thrombocytopenia, 1 had grade 3 neutropenia, and 5 had grade 3 anemia. Carboplatin has define activity in endometrial carcinoma and offers a well-tolerated palliative therapeutic alternative.     

Phase II trial of cisplatin and gemcitabine in advanced squamous-cell carcinoma of the head and neck

BACKGROUND: To evaluate the toxicity profile and efficacy of cisplatin combined with gemcitabine in patients with irresectable locally recurrent or metastatic squamous cell carcinoma of the head and neck. PATIENTS AND METHODS: Gemcitabine was given at a dose of 800 mg/m2 on days 1, 8 and 15, plus cisplatin at a dose of 50 mg/m2 on days 1 and 8; every four weeks. RESULTS: Twenty-four patients with a median age of 59 years (range 42-74) were included. All patients were evaluable for toxicity and 22 patients were assessable for response. Eleven cases had advanced recurrent locoregional disease while 13 patients had metastatic disease. One CR (4.7%) and four PR (18%) were observed, for an overall response rate of 22.7% (95% CI: 8%-42%). The main toxicity was hematological: neutropenia grade 3-4 in 28% of the cycles and thrombocytopenia grade 3-4 in 16%. The most significant non-hematological toxicity was asthenia grade 2-3 in 24% of the cycles. CONCLUSIONS: This cisplatin plus gemcitabine combination schedule has a favourable toxicity profile with a discrete activity in patients with locally recurrent or metastatic squamous-cell carcinoma of the head and neck.     

Combined radiation therapy and cisplatin for locally advanced carcinoma of the urinary bladder

BACKGROUND: This study evaluates feasibility and results of combined treatment of cisplatin and radiation therapy for patients with inoperable invasive bladder carcinoma. METHODS: From January 1988 to October 1991, 69 patients received radiation therapy and concomitant cisplatin. Median age was 71 years. Most tumors were locally advanced and high grade. A macroscopically complete transurethral resection was performed initially in 18 patients. Dose of pelvic radiation ranged from 40 Gy to 45 Gy, and total dose to the bladder ranged from 55 Gy to 60 Gy. Concomitant continuous cisplatin infusion at a dose of 20-25 mg/m2/day for 5 days was delivered during the 2nd and 5th weeks of radiation. RESULTS: As of April 1993, the median follow-up time was 36.4 months (range, 18-70 months). Ninety-one percent of the patients completed radiation therapy as planned, and 78.3% completed two courses of chemotherapy. Despite one treatment-related death due to renal failure, toxicity was generally mild and acceptable. Sixty-three patients were evaluable for response. Forty-eight patients (76.2%) achieved a complete response. Actuarial overall 3-year survival rate was 37.1% for all patients. Among the patients who experienced complete response, the 3-year actuarial local control and disease-free survival rates were 65.4% and 56.3%, respectively. Twenty-six patients (37.7%) are alive and disease-free with bladder preservation. One patient is alive and disease-free after salvage cystectomy. CONCLUSIONS: Concomitant cisplatin and radiation therapy offers high probability of complete response and local control in patients with invasive bladder cancer unsuitable for surgery. These results provide a basis for randomized studies comparing this approach with conventional therapy for patients with operable carcinoma.     

Phase II trial of paclitaxel, ifosfamide, and cisplatin in patients with recurrent head and neck squamous cell carcinoma

PURPOSE: To assess the activity and toxicity profile of combined taxol (paclitaxel), ifosfamide, and platinum (cisplatin) (TIP) in patients with recurrent or metastatic squamous cell carcinoma (SCC) of the head and neck. PATIENTS AND METHODS: Recurrent or metastatic head and neck SCC patients received paclitaxel 175 mg/m2 in a 3-hour infusion on day 1; ifosfamide 1,000 mg/m2 in a 2-hour infusion on days 1 through 3; mesna 600 mg/m2 on days 1 through 3; and cisplatin 60 mg/m2 on day 1, repeated every 3 to 4 weeks. All were premedicated with dexamethasone, diphenhydramine, and cimetidine. Prophylactic hematopoietic growth factors were not permitted. RESULTS: Fifty-two patients were assessable for response and toxicity; 53 for survival (local-regional recurrence alone in 57% and distant metastasis with or without local-regional recurrence in 43%). Overall response rate was 58% (30 of 52) of patients; complete response rate was 17% (nine of 52) of patients, with six complete responses that continued for a median 15.7+ months. Median follow-up of all patients was 17.7 months. Median survival was 8.8 months (95% confidence interval [CI] 8.1 to 17.5 months). Toxicity was relatively well tolerated and caused no deaths. The most frequent moderate-to-severe toxicity (90% of patients) was transient grades 3 to 4 neutropenia; neutropenic fever occurred in 27%. Grade 3 peripheral neuropathy occurred in three patients, none had grade 4. Grade 3 mucositis occurred in only one patient, none had grade 4. CONCLUSION: TIP had major activity in this setting, with a 58% objective response rate, 17% complete response rate, durable complete responses (six of nine persisting), and relatively well-tolerated toxicity, with no toxic deaths. The activity of TIP, a novel taxol-cisplatin-based regimen, in recurrent or metastatic head and neck SCC should be confirmed in a phase III trial.     

The fate of patients with locally advanced bladder cancer treated conservatively with neoadjuvant chemotherapy, extensive transurethral resection and radiotherapy: 10-year experience

PURPOSE: We assess the results of bladder preservation for infiltrating bladder cancer. The potential for neoadjuvant chemotherapy followed by extensive transurethral resection and radiotherapy was evaluated in 40 patients with T2-T4a G2-G3 bladder carcinoma. MATERIALS AND METHODS: From 1983 to 1995, 40 patients with bladder cancer underwent bladder sparing treatment, consisting of neoadjuvant chemotherapy, extensive transurethral resection and radiotherapy. Most patients had T3G3 cancer. A deep transurethral resection biopsy was performed before and after chemotherapy, and an extensive transurethral resection was repeated at the end of radiotherapy. Of the patients 30 received cisplatin and methotrexate and 10 also received vinblastine. Total dose of radiotherapy was 60 to 65 Gy. Recurrent superficial tumors were treated transurethrally. Radical cystectomy was considered for persistent or recurrent invasive disease. RESULTS: Complete response occurred in 19 patients (47.5%) after chemotherapy, and in 8 patients after transurethral resection and radiotherapy (67.5%). Within 10 years 8 responding patients (30%) had local recurrences and 3 underwent cystectomy. Of the patients 14 (35%) are alive, including 13 with no evidence of disease (mean survival 65 months), 5 died of unrelated disease and 21 (52.5%) died of distant metastases (mean survival 28 months). Of the 21 patients 14 had residual tumor after radiotherapy, 3 presented with distant metastases after vesical infiltrating recurrence and 4 had distant metastases in the absence of locoregional recurrence. In 22 patients (55%) the bladder was salvaged. Patients with complete response to chemotherapy had a low risk for recurrent infiltrating tumors and metastases. CONCLUSIONS: Complete tumor control was maintained at 5 years in more than 50% of the patients treated conservatively. Bladder salvage is feasible in select patients.     

Cisplatin plus oral etoposide in the treatment of patients with advanced small cell lung cancer. Japan Clinical Oncology Group

BACKGROUND: Etoposide is a highly schedule-dependent drug. We investigated combination chemotherapy of oral etoposide and intravenous cisplatin for small cell lung cancer (SCLC). METHODS: Fifty-seven patients with SCLC with extensive disease (ED) or limited disease (LD) with pleural effusion registered in the 21 institutions of the Japan Clinical Oncology Group were treated with oral etoposide 40 mg/m2/d for 21 days and cisplatin 80 mg/m2 on day 1 of every 28-period day. The entry period was between February 1992 and August 1995. The actual percentages of patients treated with etoposide were 93.6, 89.5, 92.3 and 96.9% in the first, second, third and fourth cycles, respectively. RESULTS: Nine patients (15.8%) achieved a complete response resulting in an overall response rate of 82.5% (95% confidence interval, 70.1-91.3%). Leukopenia and thrombocytopenia of grade 3 or 4 were observed in 36 (49.1%) and 8 (14.0%) patients, respectively. Anemia of grade 3 or 4 occurred in 28 (49.1%) patients. Nausea, vomiting, anorexia and alopecia were common adverse events. One patient died of hemoptysis due to grade 4 thrombocytopenia. The mean survival time was 47.0 weeks. CONCLUSIONS: This dose and schedule of administration of etoposide in combination with cisplatin are considered to be clinically active. However, prolonged gastrointestinal toxicity of oral etoposide was a problem in comparison with the standard etoposide platinum regimen given by intravenous administration.     

Studies on the phototoxic effects of oral antidiabetics and diuretics

Combined chemoradiotherapy (CT/RT) treatments appear to yield better results for advanced tumours of the head and neck than do conventional therapies. In the present study, CT/RT was used preoperatively in unresectable tumors of the oral cavity and oropharynx. Forty patients were entered prospectively into a phase II study. Treatment consisted of three cycles of chemotherapy with cisplatin and 5-day infusion of fluorouracil (FU), and the addition of simultaneous radiotherapy (30 Gy) from the second to third cycles. Patients with resectable residual disease or complete clinical response underwent surgery. All patients later received a second phase of irradiation (30 Gy) and two cycles of chemotherapy only in responders. During the first phase of treatment, 22 (55%) patients presented mucositis grades III-IV. Mean weight loss was 7%. Twelve patients were admitted for parenteral nutrition. Thirty-six (90%) patients obtained clinical response, which was complete in 15 (37%). Thirty-two of the 40 underwent surgery. The percentage of pathologic complete responses (PCR) was 35% (14 patients). With a median follow-up of 21 months, the median survival of patients was 23 months, and 19 (47%) of them are disease-free. A high PCR rate was attained with this treatment regimen. Toxicity was significant, but tolerable with adequate support measures.     

Concomitant infusion cisplatin and hyperfractionated radiotherapy for locally advanced nasopharyngeal and paranasal sinus tumors

PURPOSE: This is a prospective study to improve the therapeutic ratio in the treatment of patients with locally advanced nasopharyngeal and paranasal sinus tumors by using split-course concomitant infusion cisplatin chemotherapy and hyperfractionated radiotherapy. METHODS AND MATERIALS: From 1983 to 1993, 21 patients with locally advanced nasopharyngeal and paranasal sinus tumors (T3 and T4, or recurrent tumors involving the facial bones and/or the base of the skull) were treated with a regimen of split-course hyperfractioned radiotherapy (1.2 Gy/fraction/bid) and concomitant infusion cisplatin (5-10 mg/m2/24 h). The therapy was given in three separate 2-week sessions with 1 to 2 week breaks between sessions. Seventeen of 21 patients were treated with curative intent with cumulative radiation doses ranging from 64.8 to 70.8 Gy. Four patients were treated with palliative intent to a total dose of less than 60 Gy or to a limited field due to previous irradiation. RESULTS: Sixteen of 17 patients (94%) treated curatively achieved a complete response. Of the 16 patients who achieved complete response, 7 patients (50%) were alive at the time of analysis (36 to 126 months). One patient was alive at 4 years with no evidence of disease, and died in 10 years at the age of 80 of unknown cause. Two patients died of local recurrence at 21 and 45 months and one patient died of a cerebrovascular accident at 12 months with disease status unknown. Five patients died of distant metastases. The one patient who had a partial response died in 25 months with local disease and metastases to the bone and lung. Four patients that were previously irradiated received a reduced total dose or treated to a limited irradiation field. All had near complete responses, but died within a year of treatment, with the exception of one patient who died at 23 months. Acute reactions included intense erythema of the mucosa in all patients. Five of 21 (23%) developed punctate mucositis and 3 of 21 (14%) developed confluent mucositis. Hematologically, one patient developed neutropenia (1800 WBC/mm3) and one developed thrombocytopenia (38,000/mm3). A rising creatinine was observed in three patients (2.0, 1.7, 1.7) all of whom were treated with the higher 10 mg/m2/day dose of infusional cisplatin. In all three of these cases, the creatinine slowly returned to normal over a 6-month period. Hormonal evaluations were performed in three patients and all were within normal ranges. There was no evidence of neck fibrosis or trismus. One patient with gross recurrent disease of the orbit developed blindness of the involved eye due to corneal opacification. The orbital area had been reirradiated in this patient. CONCLUSIONS: Concomitant infusion cisplatinum with hyperfractionated radiation improved tumor control, but did not increase normal tissue injury. Acute reactions were minimized by splitting the treatment with a 1- to 2-week break after each 2 weeks of radiation treatment. Late complications were not increased by using a hyperfractionated radiation regimen. The local failure rate was only 18% (3 of 17 patients), but the distant failure rate was 35% (6 patients). Further investigation is needed to prove if adjuvant chemotherapy after concomitant chemoradiation improves survival by decreasing the distant failure in such advanced cases.     

Distributed clinical neurophysiology

We have performed a clinical phase I trial of a combination treatment with paclitaxel given as 3-hour infusion and cisplatin to determine the maximum tolerated dose and the dose-limiting toxicity in patients with recurrent or metastatic squamous cell carcinoma of the head and neck. Treatment was repeated every 21 days. Doses administered ranged from 135 mg/m2 paclitaxel/75 mg/m2 cisplatin to 250 mg/m2 paclitaxel/100 mg/m2 cisplatin. Twenty-four patients have been entered into this study. The maximum tolerated dose was determined to be 225-250 mg/m2 paclitaxel/100 mg/m2 cisplatin. The dose-limiting toxicity of this regimen was myelosuppression (granulocytopenia). Neurosensory and neuromotor toxicity was moderate. However, analyses of threshold electrotonus studies indicated subclinical neurotoxicity in most patients. One patient receiving 200 mg/m2 paclitaxel/100 mg/m2 cisplatin developed grade 3 motor-neurotoxicity. Orthostatic hypotension was observed in 8 patients receiving doses of 200 mg/m2 paclitaxel/100 mg/m2 cisplatin or higher. Objective responses were observed at paclitaxel 175 mg/m2/ cisplatin 100 mg/m2 (n = 5; complete response in 1 patient), paclitaxel 200 mg/ m2/cisplatin 100 mg/m2 (n = 3; partial response in 3 patients) and at paclitaxel 225 mg/m2/cisplatin 100 mg/m2 (n = 8; partial response in 1 patient). Eleven additional patients had stable disease. We conclude that paclitaxel administered as a 3-hour infusion followed by cisplatin is an active regimen in advanced head and neck cancer and that orthostatic hypotension may be a potentially significant clinical toxicity.     

Phase II trial of paclitaxel and cisplatin in women with advanced breast cancer: an active regimen with limiting neurotoxicity

PURPOSE: A phase II study of paclitaxel and cisplatin in patients with advanced breast cancer was performed to determine the objective response rate and make further observations about the toxicity of this regimen. PATIENTS AND METHODS: Patients were required to have histologically proven adenocarcinoma of the breast with no more than one chemotherapeutic treatment for advanced disease. Treatment consisted of paclitaxel 200 mg/m2 administered as a 24-hour intravenous (i.v.) infusion followed by cisplatin 75 mg/m2 i.v. Patients received granulocyte colony-stimulating factor (G-CSF) 5 micrograms/kg subcutaneously on day 3 until WBC recovery. Cycles were repeated every 21 days. Patients continued to receive therapy until disease progression or unacceptable toxicity. RESULTS: Forty-four patients entered the trial. Forty-two patients were assessable for response. Nineteen patients (43%) had no prior chemotherapy and 41 had no chemotherapy for metastatic disease. The median number of cycles administered per patient was five (range, one to seven). There were five complete responses (CRs) (11.9%) and 17 partial responses (PRs) (40.5%), with an overall response rate of 52.4% (95% confidence interval [CI], 36.4% to 68.0%). Nine patients had stage III disease. The response rate for this group was 66.7% (95% CI, 33.0% to 92.5%), with three CRs and three PRs. Among 35 patients with stage IV disease, there were two CRs and 14 PRs, with an overall response rate of 48.5% (95% CI, 30.8% to 66.5%). Overall, the median response duration was 10.6 months. Thirty patients (68%) developed transient grade 4 neutropenia. Cumulative neuropathy was the major dose-limiting toxicity. After five cycles of chemotherapy, 96% of patients had at least grade 1 neurotoxicity and 52% had at least grade 2 neurotoxicity. One patient had a toxic death after cycle 1 of therapy. CONCLUSION: The combination of paclitaxel and cisplatin as first-line chemotherapy for women with advanced breast cancer is an active regimen. However, the cumulative neurotoxicity was significant and dose-limiting in the majority of patients.     

Graves'' ophthalmopathy and tobacco smoking

BACKGROUND: Despite standard treatment, surgery and/or radiotherapy, most patients with muscle invasive bladder carcinoma die early of distant metastasis. CMV chemotherapy has demonstrated a high response rate with moderate toxicity in advanced bladder carcinoma. In an attempt to eradicate undetectable metastatic disease and to avoid cystectomies, 36 patients were given up-front CMV. MATERIALS AND METHODS: The patients were 34 males and 2 females with a median age of 62 years (45-75); performance status 0-1 (WHO) in 34 patients; histology: 34 transitional carcinomas and 2 anaplastic carcinomas (grade II: 8, grade III: 28). Clinical staging was T2-3a: 19 patients, T3b: 14 patients and T4: 3 patients. Nineteen patients had complete trans-urethral resections (TUR) at diagnosis. The multimodal protocol started with 3 CMV courses (cisplatin 100 mg/m2 i.v. d 1, methotrexate 30 mg/m2 i.v. d 1, 8 and vinblastine 4 mg/m2 i.v. d 1, 8 every 3 weeks). Patients who yielded clinical complete responses (cCR) by cystoscopy, TUR biopsies and imaging techniques were given 3 additional courses. Cystectomy was performed in non-cCR patients and as salvage treatment. RESULTS: Following 3 CMV cycles, 29 patients (81%) responded (20 cCR and 9 cPR) and 7 (19%) did not (NR). Currently, with a median follow-up of 23.5 months (13-59), 13 have died and 23 are alive, 12 of whom retain their bladders. The projected overall survival is 51% at 4.5 years. Grade 3-4 hematological toxicity was presented in 8% of the cycles. No toxic deaths were observed. CONCLUSION: The CMV regimen, after TUR, produces a high response rate with tolerable toxicity. Bladders could be preserved in half of the CR patients.     

Chemotherapy for cervical carcinoma: factors determining response and implications for clinical trial design

PURPOSE: To identify characteristics that predict response to chemotherapy in patients with advanced or recurrent squamous cell carcinoma of the cervix. PATIENTS AND METHODS: Between January 1986 and May 1996, 190 chemotherapy-naive patients with advanced or recurrent squamous cell carcinoma of the cervix not amenable to curative radiation therapy or surgery were treated on 14 different chemotherapy protocols at M.D. Anderson Cancer Center. Patient's charts were retrospectively reviewed for patient demographics, tumor and treatment characteristics, and patterns of response and survival. RESULTS: Of 190 patients, 22 had advanced or persistent disease and 168 had recurrent disease. Patients were treated with platinum-based (n=95) and non-platinum-based (n=95) regimens. The overall response rate was 20.0% (4.2% complete response; 15.8% partial response), with a median response duration of 4.8 months. Race, socioeconomic class, tumor stage and grade, mode of primary treatment, time from primary diagnosis to disease recurrence, initial performance status, and use of platinum-based therapy were not significant predictors of response. Age at time of chemotherapy (P=.001) and site of recurrence (P=.044) were significant determinants by multivariate analysis. Patients who were older were more likely to respond to therapy, and the response rate for patients in whom disease recurred outside the irradiated field was 25.2%, compared with a 5.3% response rate for patients with recurrent disease limited to a previously irradiated field. CONCLUSION: The site of disease recurrence and patient age should be taken into account when designing chemotherapy trials and also when considering chemotherapy in the patient with recurrent cervix cancer.     

The promoting effect of tumour necrosis factor alpha in radiation-induced cell transformation

The aim of this study was to evaluate the efficacy and safety of gemcitabine, a pyrimidine antimetabolite, in the treatment of advanced transitional cell carcinoma of the urinary tract. 35 patients with unresectable or metastatic transitional cell carcinoma of the urinary tract previously treated with a platinum-based regimen were studied. Gemcitabine was administered at a dosage of 1200 mg/m2 as a 30-min intravenous infusion on days 1, 8 and 15, repeated every 28 days. 31 patients were evaluable for efficacy. 4 patients achieved a complete response (12.9%), 3 a partial response (9.6%) and 13 (42%) were stable for at least 4 weeks (overall response 22.5%; 95% confidence interval 8-37%). The median response duration was 11.8 months (range 3.6-17.7 + months) and median survival for all patients entered was 5 months (range 2-21 + months). 2 patients with complete response are still alive with no evidence of disease after 14 and 21 months. Gemcitabine also provided subjective symptomatic relief from pain, cystitis, dysuria, haematuria and peripheral oedema. Patients experienced little WHO grade 3-4 toxicity, with anaemia in 8 patients (23%), thrombocytopenia in 5 (14.2%), leucopenia in 4 (11.4%) and neutropenia in 7 (20%). WHO grade 3-4 hepatic toxicity occurred in 4 patients (11.4%) and transient elevations of transaminase was noted in 3 (8.6%). No patient had WHO grade 3-4 elevation of serum creatinine level. There was no WHO grade 4 symptomatic toxicity and no alopecia was noted. Transient influenza symptoms with gemcitabine occurred in 18 patients (51.4%) with 13 patients (37.1%) experiencing fever (2.9% WHO grade 3). In conclusion, gemcitabine is an new active agent for the treatment of transitional cell carcinoma of the urinary bladder with a mild toxicity profile; it warrants further investigation in combination with cisplatin in chemotherapy naive patients.     

Management of recurrent meningeal hemangiopericytoma

BACKGROUND: Meningeal hemangiopericytoma is an uncommon neoplasm with a high propensity for recurrence. The purpose of this study was to analyze the efficacy of different treatment options in patients with recurrent disease. METHODS: The records of all patients with recurrent meningeal hemangiopericytoma treated at the study institution between 1976 and 1996 were reviewed. RESULTS: Thirty-four consecutive patients were studied. The mainstay of treatment was brain surgery in 21 patients (62%); the median time to recurrence from surgery was 12 months. Ten patients (29%) had 20 recurrent central nervous system (CNS) lesions treated by stereotactic radiosurgery. Of these, 3 previously nonirradiated patients (all with lesion size < 25 mm) achieved a complete response, which persisted at a median of 3 years. In 14 lesions (70%) a partial response (PR) occurred with a median duration of 12 months, whereas 3 lesions (15%) remained stable. Two patients with inoperable CNS lesions received external beam radiation therapy and both had PRs lasting 14 and 24 months, respectively. Nine patients (26%) received radiation therapy for metastatic disease. Of these, seven patients remained stable with good symptomatic relief, and two patients experienced tumor progression. Chemotherapy with doxorubicin-containing regimens was administered in 7 patients (21%); there was only 1 PR that lasted 8 months. The median survival from first recurrence was 4.6 years. CONCLUSIONS: Surgical management is important for the successful treatment of patients with recurrent meningeal hemangiopericytoma. Radiosurgery plays a definite role in the treatment of smaller recurrent CNS lesions. Radiation therapy is helpful in the management of inoperable tumors. More effective chemotherapeutic agents are needed.     

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

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

Randomized study of zorubicin versus zorubicin-cisplatin in undifferentiated carcinoma of the nasopharynx (UCNT)

BACKGROUND: The most active chemotherapy regimens in UCNT were those combining anthracyclines (doxorubicin or epirubicin) and cisplatin. Our previous pilot study on 37 patients treated with the zorubicin-cisplatin combination with a RR of 67% and literature data about other anthracyclines such as epirubicin achieving a response rate of over 50% were the basis of this randomized study comparing efficacy and toxicity of the combination vs. zorubicin as monotherapy. PATIENTS AND METHODS: A total of 80 patients entered the study. The diagnosis of UCNT was confirmed by two independent pathologists. All patients had their primary tumors in the nasopharynx. The patients were randomized in two groups: group A (zorubicin 325 mg/m2, day 1), and group B (zorubicin 250 mg/m2, day 1 and cisplatin 30 mg/m2, days 2-5). The inter-cycle interval was four weeks. The two groups were well balanced according to sex, age, stage Ho and TNM stage. RESULTS: Group A: 40 patients included, 34/40 evaluable for activity. Activity on evaluable patient basis: CR 4/34 (11.75%), PR 4/34, SD 14/34, PD 12/34, response rate 8/34 (23.5%); response rate on intent to treat basis 8/40 (20%). Toxicity: granulocytopenia grade 3-4 6/40, thrombocytopenia grade 3-4 2/40, no febrile neutropenias, nausea/vomiting any grade 3/40, cardiac toxicity any grade (rhythm) 3/40 other toxicities minor or absent. Group B: 40 patients included, 36/40 evaluable for activity. Activity on evaluable patient basis: CR 10/36 (27.78%), PR 17/36, SD 3/36, PD 6/36, response rate 27/36 (75%); response rate on intent to treat basis 27/40 (67.5%). Toxicity: granulocytopenia grade 3-4 10/40, thrombocytopenia grade 3-4 8/40, two febrile neutropenias, nausea/vomiting any grade 13/40, other toxicities mild or absent. Of the group of patients achieving a CR, four relapsed following 7, 11, 22 and 23 months, one was lost to follow-up, one died after six months from fulminant hepatitis B and eight are in complete remission lasting for 30+ to 66+ months. Following CR achievement none received any consolidation radiotherapy, and the projected five years of freedom from relapse for complete responders is about 60%. CONCLUSION: Zorubicin is an effective drug in UCNT and its combination with cisplatin has a significant activity and an acceptable toxicity.     

A phase II study of gemcitabine in platinum pre-treated patients with advanced epithelial ovarian cancer

BACKGROUND: Most patients with advanced ovarian cancer will relapse following platinum-based combination chemotherapy and be considered for second-line treatment. Gemcitabine, a nucleoside analogue, is active against a range of solid tumors. This phase II study investigated the activity of single-agent gemcitabine in patients with recurrent ovarian cancer. PATIENTS AND METHODS: Thirty-eight patients with FIGO stage III (34%) or IV (64%) ovarian cancer who were previously treated with platinum-containing regimens were enrolled. Patients received 1200 mg/m2 gemcitabine on days 1, 8 and 15 of a 28-day cycle. RESULTS: Patients completed an average of 3.6 cycles. Two complete and three partial responses were seen in 36 evaluable patients, for an overall response rate of 13.9% (95% CI: 4.7%-29.5%). The median survival time was 6.7 months. Toxicities were generally mild. The most common were grade 3-4 neutropenia and grade 3 leukopenia reported in 23.7% and 10.5% of patients, respectively. One patient had grade 4 pulmonary toxicity. CONCLUSION: Single-agent gemcitabine is active and well tolerated in patients with recurrent ovarian cancer.     

Late complications after open carpal tunnel decompression

BACKGROUND: The NCIC Clinical Trial Group has an ongoing interest in assessing investigational agents in minimally pretreated patients with malignant glioma. Topotecan is one of the first topoisomerase I inhibitors to enter clinical trials and has shown early evidence of activity in several solid tumors. We have conducted a phase II trial of topotecan in patients with malignant glioma. METHODS: Adults with malignant glioma and recurrent contrast enhancing measurable disease (> or = 2 x 2 cm) were eligible. Topotecan 1.5 mg/m2 i.v. was given daily x five days every three weeks. Response and toxic effects were assessed at the end of each cycle. RESULTS: Thirty-one patients were entered onto the study: fifteen had glioblastoma, 16 anaplastic astrocytoma, all had prior radiation, 15 prior chemotherapy, and all were assessable for response and toxicity. Two patients (6%) responded: one had a complete radiographic response, but died with neutropenic sepsis, and the second had a prolonged partial response (> 97 weeks). Twenty-one patients (68%) had stable disease for five to 86 + weeks (median 19) and eight (26%) had progressive disease after one cycle. Toxicity was primarily hematologic; 18 (58%) had grade 4 neutropenia (< 0.5 x 10(9)/1), usually brief, and three (10%) grade 4 thrombocytopenia (< 25 x 10(9)/1). Twelve of 109 cycles (11%) were given at reduced dose. CONCLUSIONS: Topotecan in this dose and schedule has only modest activity in recurrent glioblastoma and anaplastic astrocytoma.     

Tropisetron in the prevention of acute and delayed nausea and vomiting over six courses of emetogenic chemotherapy

Tropisetron (Navoban") suppresses nausea and vomiting induced by cancer chemotherapy by antagonizing central and peripheral 5-HT3 receptors. In this open-label study, tropisetron was evaluated in 873 patients who were either refractory to antiemetic treatment during previous chemotherapy or at high risk of emesis as a result of current chemotherapy. The most commonly used agents alone or in combination were cyclophosphamide (35%), fluorouracil (30%), carboplatin (24%) and cisplatin (21%). The primary tumors were breast cancer (27%), lung cancer (16%), gynecological cancers (12%) and lymphoma (9%). Tropisetron was administered as a 15 min infusion prior to chemotherapy and an additional oral 5 mg dose was taken by 80% of the patients on subsequent days. During course 1, complete response to tropisetron was obtained in 64% of patients on day 1, 54% on day 2, 63% on day 3, 71% on day 4 and 77% on day 5. Very similar response rates were found for the six chemotherapy courses. There were few failures after complete and partial response, at maximum 3 and 15%, respectively. Moreover, 24-38% of those with partial response and 7-29% of those with failure could achieve a complete response during the following cycle. The treatment was well tolerated, the most frequently reported adverse events being constipation (3.7%) and headache (2.6%).