Cisplatin-based Combination Chemotherapy Research Articles

Non-surgical treatment of advanced non-small cell lung cancer in Japan.

The cisplatin-based conventional combination chemotherapy has been shown to prolong survival of patients with advanced non-small cell lung cancer (NSCLC), but the treatment effect is only modest and of little clinical significance. Several promising 'new-generation' anti-cancer drugs, such as taxanes, vinorelbine, gemcitabine and irinotecan, have offered both chance and challenge to develop effective chemotherapy against NSCLC. In Japan, large-scale phase III trials of cisplatin-irinotecan combination regimen vs. conventional chemotherapy have been conducted; patient accrual has been completed and the final results will be presented in a couple of years. Other new agents will also be available by the end of 1999, and it will be our important task to evaluate those drugs efficiently. The current standard treatment strategy against unresectable stage III NSCLC is chemo- radiotherapy. However, there remain many questions to be answered through well-designed clinical trials. Those include optimal timing and schedule of the chemoradiotherapy, dose and fractionation of radiation and best chemotherapy regimen. An important randomized trial of concurrent vs. sequential chemoradiotherapy has been conducted in Japan, which has suggested that the concurrent schedule has survival benefit. Many trials of concurrent chemoradiotherapy with the new agents are currently performed or planned, but potential toxicity of the concurrent chemoradiotherapy must be carefully evaluated.

Factors that influence the antiemetic activity of metoclopramide to cisplatin based chemotherapy.

Some clinical parameters play a role in developing effective antiemetic therapy. In the present study, 310 patients entered and 301 were evaluable. They received cisplatin based combination chemotherapy (100 mg/m2), with antiemetic therapy based in metoclopramide, at a standard dose and schedule (2 mg/kg in 5 doses). Patient characteristics such as age, sex, performance status (Karnofsky), site of primary tumor, weight loss >15%, previous chemotherapy, previous radiotherapy, history of vomiting during pregnancy, additional drugs (dexamethasone, alprazolam), in the antiemetic regimen were included in the evaluation. We also studied the manifestation of anxiety and depression and the presence of psychosocial problems related to therapy, evaluated them with specific psychological indexes modified for our study. We evaluated incidence of vomiting, retches, and nausea, with several scales. We distinguished three groups of factors influencing nausea and vomiting. Factors that predicted for increased nausea and vomiting was gender (women), stress and age (younger patients experienced more prolonged duration and higher grades of nausea). The addition of alprazolam (a sedative drug) and dexamethasone, was associated with decreased incidence of nausea and vomiting. The weight loss (increased nausea and decreased vomiting control according to Gralla's scale). Previous chemotherapy decreased the number of patients without nausea and vomiting control according to Gralla's scale. Patients with previous radiotherapy presented an increased grade of nausea. Patients with head and neck cancer presented less nausea with shorter duration, less frequent episodes of vomiting. Patients with ovarian cancer presented increased mean number of retches. In conclusion, despite difficulties in assessing nausea and vomiting among clinical trials, several factors, especially stress, gender, weight loss, additional drugs (corticosteroids and sedatives) may play an important role in modulating the antiemetic response.

Expression of γ-glutamyl transpeptidase in stage III and IV ovarian surface epithelial carcinomas does not alter response to primary cisplatin-based chemotherapy

OBJECTIVE: γ-Glutamyl transpeptidase activity has been shown to be essential for the nephrotoxicity of cisplatin. The purpose of this study was to determine whether expression of γ-glutamyl transpeptidase in ovarian carcinomas is necessary for the antitumor effect of cisplatin. STUDY DESIGN: Tumor tissue from 18 patients with stage III or IV ovarian serous papillary carcinoma or poorly differentiated adenocarcinoma was analyzed for expression of γ-glutamyl transpeptidase by histochemical or immunohistochemical staining. Response to cisplatin-based combination chemotherapy was evaluated on the basis of clinical response, progression-free interval, and survival. RESULTS: γ-Glutamyl transpeptidase expression in the tumors ranged from 0% to 100% of the tumor cells γ-glutamyl transpeptidase positive. Patient survival ranged from 15 months to 9 years. Twelve of the 18 patients had a complete response to the initial course of cisplatin-based combination chemotherapy. There was no statistically significant correlation between either response or time to relapse and γ-glutamyl transpeptidase expression. However, there was a correlation between high levels of γ-glutamyl transpeptidase in the tumor and acute ototoxicity in patients treated with cisplatin. Expression of high levels of γ-glutamyl transpeptidase in the tumor was also found to be associated with shorter patient survival, suggesting that γ-glutamyl transpeptidase might have a role in resistance to drugs used in second- and third-line therapy. CONCLUSIONS: Expression of γ-glutamyl transpeptidase in ovarian serous papillary or poorly differentiated adenocarcinomas is not necessary for the antitumor activity of cisplatin. A correlation was found between high levels of γ-glutamyl transpeptidase in the tumor and both increased ototoxicity from cisplatin and decreased patient survival. These data suggest that administering an inhibitor of γ-glutamyl transpeptidase activity to block the nephrotoxicity of cisplatin would not interfere with its therapeutic effect. (Am J Obstet Gynecol 1998;179:363-7.)

Treatment of patients with metastatic urothelial carcinoma and impaired renal function with single-agent docetaxel

Objectives. To evaluate the efficacy and toxicity of single-agent docetaxel in patients with metastatic urothelial carcinoma and impaired renal function. Methods. Eleven consecutive patients previously untreated for metastatic disease with renal impairment (median serum creatinine level of 2.6 mg/dL) were treated with intravenous docetaxel 100 mg/m 2 for 1 hour every 21 days. Granulocyte colony-stimulating factor was administered at a dose of 5 μg/kg/day subcutaneously from days 5 to 14. Results. Five of 11 patients achieved a partial response, with time to progression of responding patients ranging from 5 to 22 months or more. The median overall survival rate was 11 months. Renal function improved in 5 of 8 patients with tumor-related renal impairment. Toxicity was primarily hematologic, with 5 patients developing grade 3 or 4 neutropenia; nonhematologic toxicities were manageable. Conclusions. Our preliminary data indicate that single-agent docetaxel therapy may represent an effective therapeutic alternative for patients with advanced urothelial carcinoma and renal insufficiency precluding cisplatin-based combination chemotherapy.

Ovarian Mixed Germ Cell Tumor Composed of Polyembryoma and Immature Teratoma

We report the case of a 41-year-old woman with ovarian mixed germ cell tumor which was composed of polyembryoma and immature teratoma and who had high serum levels of α-fetoprotein (AFP) and human chorionic gonadotropin (hCG). By immunohistochemical methods, AFP was found in yolk sac cells of the embryoid bodies and immature hepatoid tissues, and hCG was found in giant syncytiotrophoblastic cells. She was treated with surgery followed by cisplatin-based combination chemotherapy. She is well, and her serum levels of AFP and hCG have not been elevated for more than 4 years after the treatment.

Role of adjuvant chemotherapy in the treatment of invasive carcinoma of the urinary bladder.

The standard treatment for patients with muscle-invasive carcinoma of the urinary bladder is radical cystectomy. While radical cystectomy cures many patients with this tumor, almost 50% of them will develop metastatic disease. Adjuvant chemotherapy has been proposed for these patients in an attempt to reduce the probability of relapse and to improve survival. To assess whether adjuvant chemotherapy does benefit patients with muscle-invasive bladder cancer, we reviewed all phase II and III studies published in the English literature over the last 20 years. A review of all published reports was facilitated by the use of Medline computer search and by manual search of the Index Medicus. Several comparative, nonrandomized studies have indicated that adjuvant chemotherapy may prolong disease-free survival. Four randomized studies have been conducted and all had a suboptimal patient accrual. Three studies used a cisplatin-containing combination chemotherapy and included primarily patients with non-organ-confined transitional-cell carcinoma (TCC) of the bladder. All three studies indicated that adjuvant chemotherapy improved disease-free survival and two of them also showed improvement in event-free survival and overall survival, respectively. Published series have been unable to establish an undisputed benefit of adjuvant chemotherapy over radical cystectomy alone for muscle-invasive bladder cancer. The interpretation of the available data is compromised by several methodologic and statistical problems. Thus, adjuvant chemotherapy cannot be considered as a standard treatment for all patients with muscle-invasive carcinoma of the bladder. Well-designed prospective randomized studies are needed to clarify the role of adjuvant chemotherapy in this disease. However, outside a protocol setting, there is some evidence that patients with extravesical disease or with lymph node involvement may benefit from adjuvant treatment with cisplatin-based combination chemotherapy. No data support such an approach for patients with muscle-invasive but organ-confined bladder cancer.

Cisplatin-based chemotherapy in advanced seminoma: the Institut Gustave Roussy experience.

The aim of this study was to report the results of cisplatin-based combination chemotherapy for patients with pure seminomatous tumours. 72 patients with advanced seminoma were treated with various cisplatin-based chemotherapy regimens. 61 (85%) patients achieved a sustained durable response. 11 relapses were observed with a median time to failure of 6 months. Overall, 60 (83%) of the 72 patients remain alive and free of disease after a median follow-up of 64 months. Initial clinical (age, site of primary, prior radiotherapy, extent of disease) and biological (serum human chorionic gonadotrophin levels, serum lactic dehydrogenase levels, p53 immunostaining) features which could be of predictive value for survival, were analysed in a univariate analysis. No variable retained statistical significance. High cure rates are expected after chemotherapy with standard cisplatin-based combinations in advanced seminoma. Renewed efforts are required to identify markers of chemosensitivity.

Clinical Experiences of Germ Cell Tumor in Cryptorchid Testis

The increased risk of malignancy occurring in the cryptorchid testis is well established. In order to investigate the management and outcome of germ cell tumor in cryptorchid testis, we retrospectively rewiewed the records of 11 patients with cryptorchid tumor treated at our hospital between January 1973 and December 1996. Mean patient age at diagnosis was 47.6 years (range, 22-80). Of these patients, 3 were found in the inguinal area and 8 in the abdomen. Six occurred in the right cryptorchid testis and 5 in the left. Four patients presented with stage I disease, 4 with stage II, and 3 with stage III. Median follow-up period was 48.0 months (range 1-163). All 3 inguinal cryptorchid tumors and 6 of 8 abdominal cryptorchid tumors were seminoma. The remaining 2 abdominal cryptorchid tumors were nonseminomatous germ cell tumor. Of the 3 patients with inguinal cryptorchid seminomas, 2 with stage I disease were treated with prophylactic radiotherapy to nodal areas and 1 with stage III disease was treated with chemotherapy. Eight patients with abdominal cryptorchid tumors were treated with multidisciplinary approaches, including radiotherapy, cisplatinbased combination chemotherapy, and surgery. The overall survival rate for patients with inguinal and abdominal cryptorchid tumor was 81.8%. Two patients with stage III disease died during treatment and the remaining 9 patients are still alive without evidence of disease

Advanced non-small cell lung cancer chemotherapy: a randomized trial of two active regimens (MVP and PE)

The treatment of advanced or metastatic NSCLC remains a controversial issue and cisplatin-based combination chemotherapy is by far the most common treatment. Two of these cisplatin-based standard combinations, MVP and PE, were compared in this study in order to evaluate their response rates and survival times. Eighty-five previously untreated NSCLC patients were randomly selected to receive either MVP or PE and 72 of these patients were eligible for evaluation for response rate and survival. Response rates for MVP were: CR 11%, PR 35%, SD 19% and PD 35% and for PE: CR 0%, PR 26%. SD 22% and PD 52%. The median survival time was 9.7 months for MVP and 6.9 months for PE. Both schedules were well tolerated. The administration of MVP in advanced NSCLC resulted in superior response rates and survival times over those produced by PE.

Cisplatin-based combination chemotherapy for elderly patients with non-small-cell lung cancer

To compare the response rates, toxicities and survival durations of elderly patients (70 years of age or more) with those of younger patients (less than 70 years of age) with non-small-cell lung cancer (NSCLC) treated with cisplatin-based chemotherapy. We analyzed retrospectively the data of 203 assessable patients entered on a prospective randomized trial of cisplatin-based combination chemotherapy. Chemotherapy consisted of three dosage regimens: (1) vindesine and cisplatin (VP); (2) mitomycin, vindesine and cisplatin (MVP); or (3) etoposide and cisplatin alternating with vindesine and mitomycin (EP/VM). A greater proportion of elderly patients had localized disease and more squamous cell carcinoma than non-elderly patients. The overall response rates were 44% in the elderly group and 28% in the non-elderly group. In the EP/VM arm, the response rate was significantly better in the elderly group than in the non-elderly group. The frequency of grade 4 leukocytopenia in the MVP and EP/VM arms in the elderly group was significantly greater than in the non-elderly group (P < 0.05). No differences were found in nonhematological toxicities between the two groups. There was no difference in overall survival between the groups. Elderly patients treated with mitomycin-containing regimens have higher hematologic toxicities than younger patients. The results of this study are consistent with the previously reported pharmacologic data on mitomycin suggesting altered pharmacokinetics in elderly patients. The improved response rate in the elderly patients was probably because more elderly patients had earlier disease, squamous cell carcinoma and better performance status. Cisplatin-based chemotherapy was tolerable for most elderly NSCLC patients with good performance status.

Hexamethylmelamine as a Single Second-Line Agent in Ovarian Cancer: Follow-up Report and Review of the Literature

From December 1982 to December 1986, 52 patients with recurrent ovarian cancer were treated with single-agent HMM. Chemotherapy was given for a period of 1 year unless progression of disease or toxicity was noted. Survival was determined from the time of diagnosis to the date of death or September 30, 1992. The regimen was well tolerated with only one case of severe gastrointestinal toxicity. Nine patients were found to be clinically free of disease following completion of HMM treatment; they had initially responded to cisplatin-based therapy (i.e., potentially cisplatin-sensitive) and subsequently recurred. Four were found to have gross disease at the time of reassessment laparotomy. Three of these 9 patients are alive 81–92 months since diagnosis, having maintained disease-free intervals of up to 6 years. The median survival for the 9 patients without evidence of disease at the end of therapy was 75 months versus 9 months for the nonresponders. No patient who had progressive disease on first-line cisplatin-based combination chemotherapy (i.e., primary cisplatin-resistant) responded to second-line single-agent oral hexamethylmelamine. With a follow-up close to 10 years, our data show that hexamethylmelamine, with reasonable toxicity, can provide an extended, disease-free interval to a selected group of patients.

Mediastinal non-seminomatous germ cell tumours (MNSGCT) treated with cisplatin-based combination chemotherapy

Primary mediastinal non-seminomatous germ cell tumours (MNSGCT) constitute a rare malignancy. This study was performed to review our experience with cisplatin-based chemotherapy in patients with MNSGCT. Patients with MNSGCT treated with cisplatin-based combination chemotherapy between 1978-1995 in three university hospitals in Spain were retrospectively studied. There were 25 males and two females with a median age of 26 years (range 4-71). Fifteen patients had disease confined to the mediastinum and 12 had metastatic disease. All patients were treated with cisplatin chemotherapy regimens (PVB: 7, BEP: 6, and other regimens 12) and considered for residual mass surgery (RMS) when indicated. Eleven patients (40.7%) were rendered disease-free with initial treatment: four with chemotherapy alone, one with surgery plus adjuvant chemotherapy and six with chemotherapy plus RMS. Three of these patients relapsed at two, six and seven months. The remaining 16 had unfavourable responses (five partial response, three no change, seven progressive disease and one toxic death). Eleven patients received salvage treatment but none of them achieved a durable response. After a median follow-up of 77 months (range 1-168), 10 patients remain alive. Actuarial survival at five years is 31.7%. No patients in this series developed a haematological malignancy. Chromosomal analysis showed that 2 out of 10 patients (20%) had a 47XXY karyotype. Only patients who achieved disease-free status are likely to be cured. Therefore, new up-front strategies are needed for the treatment of MNSGCT.

Postchemotherapy resections of residual masses from metastatic non-seminomatous testicular germ cell tumors

To analyse the frequencies of histological findings, predictive factors for the presence of undifferentiated tumor and variables influencing the survival of patients with non-seminomatous germ cell tumors who underwent secondary resection of residual masses after cisplatin-based combination chemotherapy. 134 patients with a median age of 26 years (15-47) undergoing at least one surgical intervention at Hannover University Medical School were included. One hundred nine patients had received first-line chemotherapy and 25 underwent surgery after second-line chemotherapy. After first-line chemotherapy the distribution of histological findings was 52% necrosis, 27% differentiated teratoma and 21% undifferentiated tumor for 82 patients with marker negative PR (PRm-). Incompletely resected mass and failure to achieved complete tumor marker normalisation were significantly associated with the finding of undifferentiated tumor. Five-year progression-free survival rates according to histological findings were 78%, 67% and 66% for necrosis, differentiated teratoma and undifferentiated tumor. Patients with undifferentiated tumor in the resected specimen routinely received postoperative additional chemotherapy. Factors associated with a worse overall survival were progressive disease within three months, persistent AFP elevation prior to surgery, prechemotherapy elevated LDH levels or mediastinal lymph node involvement at primary diagnosis. In 8 of 27 patients (30%) undergoing multiple resections at different sites a dissimilar histology was found. In the 25 patients operated after salvage chemotherapy undifferentiated tumor was found in 80%. A five-year survival of 44% compared to 80% after first-line chemotherapy was achieved. Resection of residual tumors after first-line chemotherapy remains essential in the treatment of metastatic testicular cancer. Undifferentiated tumor may still be found in 20% of patients despite achieving PRm-after first-line chemotherapy. Necrosis is found in only 50% of marker normalized patients after first-line and approximately 30% after second-line chemotherapy. Future studies have to prove whether the combination of clinical prognostic factors and the use of PET-scanning will allow to spare subsets of patients from secondary resection.

Treatment of brain metastases in patients with testicular cancer.

Despite improved cure rates for patients with metastatic testicular cancer with cisplatin-based combination chemotherapy, patients who develop brain metastases are generally considered to possess a poor prognosis. This report summarizes the long-term results in 44 patients with brain metastases from testicular cancer treated between 1978 and 1995 at Hannover University Medical School. Histologically, 42 patients (95%) had a nonseminomatous germ cell cancer and two patients (5%) a seminoma. Thirty-nine patients (89%) had lung metastases and 37 (84%) fulfilled the criteria for advanced disease according to the Indiana University classification even without considering the brain metastases. Eighteen patients (41%) presented with brain metastases at primary diagnosis (group 1), four (9%) developed brain metastases at relapse after a previous favorable response to combination chemotherapy (group 2), and 22 (50%) developed brain metastases during or directly after cisplatin-based chemotherapy. Chemotherapy consisted of cisplatin-based combination treatment and radiotherapy was given as whole-brain irradiation of 30 to 40 Gy and in single cases combined with a boost of 10 Gy to single lesions. Overall, 10 patients achieved long-term survival (23%; 95% confidence interval [CI], 10.1% to 35.4%). The prognosis was significantly better for patients in groups 1 and 2, with six of 18 (33%) and three of four (75%) patients alive, compared with only one of 22 (5%) in group 3 (P < .01). Patients treated with either chemotherapy or radiotherapy alone did not achieve long-term survival, while nine of 28 (32%) who received treatment with both modalities with or without surgery achieved sustained long-term survival. During univariate analysis, patients with the diagnosis of brain metastases at first presentation (P < .01), patients with a single brain lesion (P < .02), and patients who received combined chemotherapy and radiotherapy (P < .03) had a significantly improved outcome. Long-term survival can be achieved in approximately 25% of patients with brain metastases from testicular cancer by combined treatment with brain irradiation and aggressive cisplatin-based chemotherapy. Patients who develop brain metastases during systemic treatment should receive only palliative radiation therapy, since sustained survival will not be reached.

Weekly gemcitabine with monthly cisplatin: effective chemotherapy for advanced non-small-cell lung cancer.

The aim of this study was to examine the efficacy of a regimen of initial gemcitabine followed by cisplatin in patients with advanced non-small-cell lung cancer (NSCLC). Fifty-three patients (36 men and 17 women; age range, 35 to 74 years) were enrolled. Patients had bidimensionally measurable disease. Gemcitabine (phase-specific agent) was administered on days 1, 8, and 15 at a dose of 1,000 mg/m2. Cisplatin (cycle-specific agent) was administered on day 15 (100 mg/m2). Chemotherapy was administered in 28-day cycles. Of 53 patients enrolled, 50 were assessable for response. The overall response rate was 52%. There were two complete responses (4%) and 24 partial responses (48%). The median survival duration was 13 months and the 1-year survival rate was 61%. The regimen was generally well tolerated. World Health Organization (WHO) grade 3 and 4 neutropenia occurred in 38.8% and 19.2% of patients, respectively. Grade 3 and 4 thrombocytopenia occurred in 13.3% and 7.7% of patients, respectively. Most patients experienced mild nausea and vomiting. Few patients had hair loss and oral toxicity was mild. Relatively few patients required dose modifications for any of the three weekly doses of chemotherapy. For the first two cycles of chemotherapy, the dose-intensity per infusion was 947 mg/m2 for gemcitabine and 85 mg/m2 for cisplatin. This regimen of gemcitabine and cisplatin was effective, with high response and survival rates and few dosage modifications during its administration. Prospective randomized studies with other cisplatin-based combination chemotherapy regimens are indicated.

Limitation of Conventional Cisplatin-Based Combination Chemotherapy for Disseminated Germ Cell Tumor: Implication for Introduction of Aggressive Treatment as an Initial Chemotherapy.

To assess the limitation of standard cisplatin-based combination chemotherapy for metastatic germ cell tumor, clinical records of 37 patients with metastatic testicular cancer and extragonadal germ cell tumor treated with primary chemotherapy were reviewed. Thirteen patients of 37 had limitation of the treatment. We categorized the mode of treatment limitation into 5 criteria according to the response of tumor marker levels and radiographic findings, and recurrence. Tumor volume was strongly associated with the limitation of the treatment. Indiana University Staging System, not Royal Marsden Hospital's classification clearly discriminated the patient with limitation of standard cisplatin-based combination chemotherapy. High dose chemotherapy was effective for patients to whom the initial chemotherapy with standard cisplatin-based regimen was effective. It did not offer any benefit to patients with refractory tumor. We conclude that it is important to introduce more aggressive chemotherapy regimens as an initial chemotherapy to patients with large volume tumor.

Cisplatin, vincristine, methotrexate, peplomycin, etoposide (COMPE) therapy for disseminated germ cell testicular tumors.

The advent of cisplatin rendered disseminated testicular germ cell tumor an often curable malignant disease. Patients with a heavy metastatic burden, however, remain poor risks; furthermore, many patients experience nausea or other adverse events. This paper reports a trial of a cisplatin-based (COMPE) combination chemotherapy regimen based on synchronization theory. Twenty patients with disseminated germ cell testicular tumors were treated with COMPE; any residual tumor mass was surgically resected. Seventeen patients (85%) achieved complete remission by chemotherapy. The actuarial overall and cause-specific 3-year survival rates were 89% and 94%, respectively. In the subset of 16 "good-risk" patients, all remain alive after a median follow-up of 43 months. Complications were quite tolerable, with nephrotoxicity in particular being extremely mild. COMPE is an effective chemotherapy regimen in patients with disseminated germ cell testicular tumors. Complications arising from this therapy are mild.

Residual mass following chemotherapy of seminoma

The residual mass so frequently found after chemotherapy of advanced seminoma may consist entirely of benign tissue or may contain residual disease amenable to adjuvant therapy. A detailed retrospective analysis was performed on 45 patients treated with cisplatin based chemotherapy for advanced seminoma between 1978 and 1994. The probability of a residual mass after chemotherapy was higher if the pre-treatment mass diameter was > 5 cm (78% versus 15%, P = 0.0009). Of 33 patients with residual masses following cisplatin chemotherapy, 4 were explored surgically showing fibrosis only, 15 were treated by adjuvant radiotherapy and 14 were managed by observation alone. Recurrence occurred in 2 of 14 patients managed by observation and in 2 of 15 managed by radiotherapy. There was no evidence that risk of recurrence was related to diameter of residual mass. Residual masses persisted following cisplatin based combination chemotherapy for seminoma in 73% of cases. In our study, recurrence was rare and there was no evidence that this was influenced by either the size of the residual mass or the use of adjuvant therapy.

Dose-intensive weekly chemotherapy for treatment of relapsed small-cell lung cancer.

This study was undertaken to determine the activity and toxicity of dose-intensive weekly chemotherapy (cisplatin, vincristine, doxorubicin, and etoposide [CODE] regimen) for previous treated, recurrent small-cell lung cancer (SCLC). The 17 patients with relapsed SCLC entered onto the study were to receive intensive weekly chemotherapy with the CODE regimen. All 17 patients had been heavily pretreated with some form of cisplatin-based combination chemotherapy. Six patients had received previous chemotherapy with CODE and one patient with cisplatin and etoposide (PE) as induction therapy. Nine patients had been treated with concurrent or sequential PE plus thoracic irradiation (TRT). The median time off chemotherapy was 6.7 months (range, 3.3 to 72). Patients were treated with 9 weeks of the CODE regimen. Response, survival, and toxicity data were noted. All 17 patients were assessable for response, survival, and toxicity. Fifteen of 17 patients (88.2%) had an objective response, with five complete responses (CRs; 29%) and 10 partial responses (PRs; 58.8%). The median durations of response and survival were 156 days and 245 days, respectively. Myelosuppression was significant, with 76% of patients developing grade 4 leukopenia. No treatment-related death was observed. The CODE regimen is highly active in the treatment of relapsed SCLC with an encouraging survival outcome.

A randomized trial of cisplatin, etoposide and bleomycin (PEB) versus carboplatin, etoposide and bleomycin (CEB) for patients with ‘good-risk’ metastatic non-seminomatious germ cell tumors

Cisplatin-based combination chemotherapy will cure 70% to 80% of patients with metastatic non-seminomatous germ cell tumors but is associated with the possibility of severe neuro-, oto- and nephro-toxicities. Carboplatin, a cisplatin analogue, is an active drug in testicular cancer with a more favourable spectrum of side effects. In a randomized trial, the German Testicular Cancer Study Group compared a combination regimen of carboplatin, etoposide and bleomycin (CEB) to standard cisplatin, etoposide and bleomycin (PEB) chemotherapy for patients with 'minimal-' and moderate-disease' non-seminomatous germ cell tumors, according to the Indiana University classification. PEB was given for three cycles at standard doses (given days 1-5), and the CEB regimen consisted of carboplatin (target AUC of 5 mg/ml x min) on day 1, etoposide 120 mg/m2 on days 1 to 3 and bleomycin 30 mg on days 1, 8 and 15. Four cycles of CEB were given, with the omission of bleomycin in the fourth cycle. Thus, the cumulative doses of etoposide and bleomycin applied in the two treatment arms were comparable. Fifty-four patients were entered on the trial, 29 were treated with PEB and 25 with CEB chemotherapy. Patients were stratified according to disease extent (minimal versus moderate) and the degree of tumor marker elevation. Thirty-two patients (59%) belonged to the group with minimal disease and low markers. No significant difference in response to chemotherapy was seen between the two arms, with CR rates of 81% for the PEB arm and 76% for CEB treatment. However, more patients treated with CEB (32% versus 13%) have relapsed after therapy, and 4 patients (16%) have died of disease progression after CEP in contrast to 1 (3%) after PEB therapy. The first interim analysis of negative events (relapse, vital tumor at secondary resection, death from disease and therapy-associated death) showed a significantly higher rate after CEB than after PEB therapy, and the trial was terminated early. After a median follow-up of 33 months for all patients, the calculation of negative events is still significantly in favour of PEB-treated patient, particularly since three late relapses > 2 years have been observed in the CEB arm (P = 0.03). This randomized trial demonstrates that even with the use of adequate doses of etoposide and full-dose bleomycin, carboplatin cannot altogether replace cisplatin in patients with testicular cancer. Treatment with the PEB regimen remains the standard approach in patients with 'good-risk' non-seminomatous germ cell tumors.