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Biomedical subjects

J T Hartmann

Publications and source records attributed to J T Hartmann.

At least 55 records · Page 3Linked to original sources
PubMed2000

The relative risk of second nongerminal malignancies in patients with extragonadal germ cell tumors.

BACKGROUND: Apart from a recognized association between extragonadal mediastinal germ cell tumors (GCT) and the occurrence of hematologic malignancies, the risk of developing second nongerminal solid tumors after the diagnosis or treatment of extragonadal GCT is unknown. METHODS: Six hundred thirty-five consecutive patients with extragonadal GCT treated at 11 centers in the U.S. and Europe during the era of cisplatin-based chemotherapy (1975-1996) were included into a large database. These patients were evaluated for the occurrence of second malignancies. RESULTS: No treatment-related leukemia was observed in 611 patients treated with chemotherapy. In 7 patients, second solid tumors were observed, resulting in a frequency of 1.86% (95% confidence interval [95% CI], 1.79-1.93%) after a median follow-up of 55 months (95% CI, 50-60 months) (annual incidence, 0.30% [95% CI, 0.14-0.59]). Four solid tumors (57%) developed in patients with primary mediastinal and 3 tumors (43%) developed in patients with retroperitoneal GCT. Three patients (43%) had a nonseminomatous and 4 patients (57%) had a seminomatous histology. Six patients had been treated with chemotherapy and one patient with radiotherapy. Six of 7 solid tumors (86%) had developed within 5 years and 7 of 7 solid tumors within 10 years of diagnosis. The median time period to the occurrence of neoplasia was 47 months (range, 9-145 months). Four cutaneous tumors were observed (melanoma, two patients; basal cell carcinoma, one patient; and squamous cell carcinoma, one patient); the other three tumors were angiosarcoma, nonsmall cell lung carcinoma, and colorectal carcinoma. The overall risk for developing a second tumor was not increased compared with an age-matched general population with a standard incidence ratio (SIR) of 1.49 (95% CI, 0.60-3.06). An elevated risk for skin tumors was observed in all extragonadal GCT patients (SIR, 4.00 [95% CI, 1. 09-10.24]), as well as in the subgroup of patients treated with chemotherapy (SIR, 5.33 [95% CI, 1.45-13.65]). CONCLUSIONS: This analysis excludes an increased biologic risk of developing second solid malignancies in patients with extragonadal GCT except for the previously reported association between primary mediastinal nonseminoma and hematologic disorders. The overall risk of developing second malignancies in extragonadal GCT patients appears to be comparable to that in patients with primary testicular carcinoma. The incremental occurrence of skin malignancies in patients treated with chemotherapy should be investigated further.

Adolescent↗
PubMed2000

Hematologic disorders associated with primary mediastinal nonseminomatous germ cell tumors.

BACKGROUND: The association between primary germ cell tumors of the mediastinum (the space between the lung pleura that contains the heart and other chest viscera) and hematologic malignancies has been described by retrospective analysis of patients treated at individual clinical centers. To better characterize the risk of hematologic disorders in patients with extragonadal germ cell tumors and to describe the clinical and biologic features of the disorders, we studied an unselected population in a large, international, multicenter database. METHODS: Six hundred thirty-five patients treated at 11 centers in the United States and Europe from 1975 through 1996 were evaluated retrospectively. RESULTS: A hematologic disorder was observed in 17 patients with germ cell tumors. All cases developed among the 287 patients with primary mediastinal nonseminomatous germ cell tumors, giving an incidence rate in this group of 2.0% (95% confidence interval [CI] = 1.1%-3.1%) per year over a median follow-up time of 3 years. The risk of developing hematologic disorders was statistically significantly increased in patients with primary mediastinal nonseminomatous germ cell tumors in comparison with the age-matched general population (standardized incidence ratio = 250; 95% CI = 140-405). The median time to onset of hematologic neoplasia was 6 months (range, 0-47 months), and the median survival after diagnosis of the hematologic disorder was 5 months (range, 0-16 months) (two-sided P<.0001, comparing survival from the time of diagnosis of the germ cell tumor of patients with and without hematologic disorders). CONCLUSION: In our study, approximately one in 17 patients with primary mediastinal nonseminomatous germ cell tumors was affected by a hematologic disorder, whereas no cases were seen among 334 patients with other extragonadal germ cell tumors. The hematologic disorder had a statistically significant impact on prognosis, with none of the 17 reported patients surviving for more than 2 years.

Adolescent↗
PubMed2000

A randomized trial comparing the nephrotoxicity of cisplatin/ifosfamide-based combination chemotherapy with or without amifostine in patients with solid tumors.

This study evaluates the degree of kidney damage during cisplatin/ifosfamide-based combination chemotherapy and its possible prevention by amifostine. Thirty-one patients with solid tumors stratified according to pretreatment were randomized to receive VIP- or TIP-chemotherapy with or without amifostine (910 mg/m2) given as a short infusion prior to cisplatin. Chemotherapy consisted of cisplatin (50 mg/m2), ifosfamide (4 g/m2) and either etoposide (500 mg/m2) (= VIP) or paclitaxel (175 mg/m2) (= TIP) repeated at 3 weekly intervals. For all patients the glomerular filtration rate (GFR) measured by creatinine-clearance, serum creatinine, electrolytes and differential urinary protein/enzyme excretion were determined prior to, during and after each cycle. A total of 62 cycles of chemotherapy were evaluable. In the amifostine-group GFR was fully maintained after application of two cycles of chemotherapy, whereas in the control group a > 30%-reduction of median GFR (108 to 80 ml/min) was observed (p < 0.001). Patients receiving amifostine had a lower degree of high molecular weight proteins excretion indicating less glomerular damage. In both groups significant increases of tubular marker profiles peaking at day 3 after chemotherapy were observed with a nearly complete reversibility of these changes prior to the next chemotherapy cycle. The number of patients with low magnesium serum levels during treatment was 17% after amifostine application versus 69% in control patients. The results seem to indicate that treatment with amifostine can preserve GFR after application of two cisplatin/ifosfamide-based chemotherapy cycles. This may be advantageous if repetitive cycles of chemotherapy or subsequent administration of high dose chemotherapy is planned.

Adolescent↗
PubMed2000

First-line high-dose chemotherapy +/- radiation therapy in patients with metastatic germ-cell cancer and brain metastases.

PURPOSE: To examine the feasibility and efficacy of first-line high-dose chemotherapy (HD-CTX) in patients with advanced metastatic germ-cell tumors (GCT) and brain metastases. PATIENTS AND METHODS: Twenty-two patients with brain metastases at initial diagnosis were identified within a cohort of two hundred thirty-one consecutive patients with advanced metastatic disease, entered on a German multicenter trial between January 1993 and July 1998. All patients received first-line HD-CTX with cisplatin-etoposide-ifosfamide (HD-VIP) followed by autologous stem-cell transplantation. Brain irradiation (BRT) with 30-50 Gy +/- 10 Gy boost was applied in patients with symptomatic CNS disease or as consolidation in case of residual CNS lesions after HD-CTX. RESULTS: A median number of 4 HD-CTX cycles (range 2-5) were applied to the 22 patients. Ten patients received HD-CTX alone and twelve patients were treated with HD-CTX plus BRT. Median duration of WHO grade 4 granulocytopenia and thrombocytopenia was seven and five days after each cycle, respectively. Non-hematologic toxicity consisted mainly of mucositis/enteritis (WHO grade 3-4 32%). Two early deaths occurred in twenty-two patients (one CNS-bleeding/one sepsis). Fourteen of twenty patients achieved a CR/PRm- status. Twenty patients (91%) responded in the brain (55% CR/36% PR). Two-year progression-free and overall survival rates were 72% and 81%, respectively. These survival rates are substantially higher compared to the available data in the literature. CONCLUSIONS: High-dose chemotherapy with autologous stem-cell support +/- BRT appears to be feasible without increased therapy-related mortality in patients with advanced metastatic GCT and brain metastases. The results achieved emphasize the high chemosensitivity of CNS metastases from GCT and suggest a potential role for dose intensification. The dose of BRT in addition to HD-CTX may be tailored to the presence of clinical symptoms and the response of CNS metastases to chemotherapy.

Adult↗
PubMed2000

A phase II study of paclitaxel, weekly, 24-hour continous infusion 5-fluorouracil, folinic acid and cisplatin in patients with advanced gastric cancer.

To evaluate the toxicity and efficacy of combination chemotherapy with paclitaxel, cisplatin and 24 h continuous infusion of 5-FU/folinic acid in patients (pts) with unresectable, locally advanced or metastatic gastric adenocarcinoma. Forty-five chemotherapy-naive pts (28 male and 17 female) with a median age of 60 years (range 35-74) were enrolled. 5-FU 2 g/m2 was given weekly over 24 h i.v. preceded by folinic acid 500 mg/m2 as a 2 h infusion. Paclitaxel 175 mg/m2 was administered as a 3 h-infusion on days 1 and 22 and cisplatin 50 mg/m2 as 1 h infusion on days 8 and 29. Six weeks of therapy (days 1, 8, 15, 22, 29, 36) followed by 2 weeks rest were considered one cycle. A median of 3 cycles (range 1-4) were administered to 45 pts assessable for response, survival and toxicity. Five pts (11%) obtained a CR and 18 pts (40%) a PR (ORR 51%; 95% CI: 35.8-66.3%). Responses were achieved in the liver, lymph nodes, lungs and at the site of the primary tumour. Nine pts (20%) had stable disease. Thirteen pts (29%) were considered to have failed treatment, 8 pts (18%) due to progressive disease and 5 pts (11%) who did not receive one complete cycle of therapy due to acute non-haematologic toxicity. The median progression-free and overall survival times were 9 months (range 1-36+) and 14 months (range 2-36+), respectively. Neutropenia WHO III(o)/IV(o) occurred in 7 pts (15%) with only 1 pt having grade IV. Additional non-haematologic WHO III(o)/IV(o) toxicities included nausea/vomiting in 5 (11%), alopecia in 22 (49%), and diarrhoea in 1 patient each (2%). Dose reductions or treatment delays were necessary in 8 pts (17%), mainly due to neutropenia. All pts were treated on an outpatient basis. The combination of paclitaxel, cisplatin and continuously infused 5-FU/folinic acid appears to be a highly active regimen for the treatment of pts with advanced gastric cancer. While the overall acceptable toxicity allows its use in the palliative setting, it may also be an attractive option to be tested for neoadjuvant or adjuvant treatment.

Adenocarcinoma↗
PubMed2000

The use of reduced doses of amifostine to ameliorate nephrotoxicity of cisplatin/ifosfamide-based chemotherapy in patients with solid tumors.

This study evaluates the degree of kidney damage during cisplatin/ifosfamide-based combination chemotherapy and its possible prevention by amifostine. Thirty-one patients with solid tumors stratified according to pretreatment were randomized to receive cisplatin/ifosfamide-based chemotherapy with or without amifostine (1000 mg absolute) given as a short infusion prior to cisplatin. Chemotherapy consisted of cisplatin (50 mg/m2), ifosfamide (4 g/m2) and either etoposide (500 mg/m2) (VIP regimen) or paclitaxel (175 mg/m2) (TIP regimen) repeated at 3 weekly intervals. For all patients the glomerular filtration rate (GFR) measured by creatinine clearance, serum creatinine, electrolytes and differential urinary protein excretion were determined prior to, during and after each treatment cycle. A total of 62 cycles of chemotherapy were evaluable. In the amifostine arm the GFR was almost completely maintained after application of two cycles of chemotherapy (121 to 108 ml/min), whereas in the control group a 30% reduction of the GFR (105 to 80 ml/min) was observed. In both groups marked increases of glomerular and tubular marker profiles peaking at day 3 after chemotherapy were found with a nearly complete reversibility of these changes prior to the next chemotherapy cycle. Patients receiving amifostine had a lower degree of hypomagnesemia, as well as a lower urinary excretion of N-acetyl-glucosaminidase and albumin, indicating less tubular damage compared to the control patients. Treatment with 1000 mg amifostine resulted in an almost complete preservation of GFR. This corresponded to a slightly reduced excretion of tubular marker proteins and a lower incidence of hypomagnesemia during chemotherapy in amifostine patients compared to controls. This dose of amifostine may be sufficient for nephroprotection in patients without pre-existing risk factors for renal damage who undergo a restricted number of chemotherapy cycles.

Adult↗
PubMed2000

UFT/leucovorin plus weekly paclitaxel in the treatment of solid tumors.

The palliation of symptoms and improvement of quality of life are important aspects of therapy in patients with incurable metastatic cancer. This article describes the preliminary results of a phase I study of uracil and tegafur, an orally available fluorouracil (5-FU) derivative combined with oral leucovorin plus weekly intravenous paclitaxel. While the daily oral dose of UFT is fixed at 300 mg/m2 plus 90 mg leucovorin on days 1 to 28, paclitaxel is escalated in 10 mg/m2 steps starting with 50 mg/m2 weekly as a 1-hour infusion. To date, 26 patients with a median age of 57 years have been entered into the protocol and have received a median 2.2 cycles of therapy. Dose level 4 (paclitaxel 80 mg/m2) has been recently completed. Major dose-limiting toxicities were fatigue syndrome (two patients) and diarrhea (five patients). Preliminary responses have been observed in three of 14 currently evaluable patients. This protocol is taking the development of protracted 5-FU administration--given orally as UFT--in combination with paclitaxel one step further, using paclitaxel in a dose-dense, weekly schedule. It is hoped that an active regimen for the outpatient treatment of solid tumors will be developed.

Administration, Oral↗
PubMed1999

Treatment of patients with cisplatin-refractory testicular germ-cell cancer. German Testicular Cancer Study Group (GTCSG).

With the use of cisplatin-based combination chemotherapy, metastatic testicular germ-cell tumors can be cured in 70% to 80% of patients. The combination of cisplatin, etoposide and bleomycine (PEB) is considered standard therapy. Patients refractory to cisplatin-based chemotherapy have a markedly poor prognosis. Several chemotherapeutic agents have been evaluated in intensively pre-treated or cisplatin-refractory patients. Neither the anthracyclines nor vinorelbine, topotecan or biological agents such as suramin and retinoic acid have demonstrated clinical activity. Paclitaxel has been evaluated at different doses and schedules and yielded a response rate of 21% (range 11-30%), with single patients achieving complete remissions. This has led to the inclusion of paclitaxel in salvage regimens in combination with cisplatin and/or ifosfamide. Two studies have evaluated gemcitabine in refractory germ-cell tumors and demonstrated a response rate of 17% (95% CI 7-28%) in 52 intensively pre-treated patients, two-thirds of whom had relapsed after previous high-dose chemotherapy plus autologous stem-cell transplantation. The non-hematological toxicity of weekly gemcitabine at doses of 1,000 to 1,250 mg/m2 was tolerable, and hematological side effects included thrombocytopenia in approximately 20% of patients. Ongoing studies in refractory germ-cell tumors performed by the German Testicular Cancer Study Group are evaluating bendamustine, an alkylating agent with activity in breast and small-cell lung cancer, and oxaliplatin, a platinum derivative with incomplete cross-resistance to cisplatin. Future trials combining new active agents may examine alternating treatment strategies in patients with poor-prognostic disease or as salvage treatment.

Antimetabolites, Antineoplastic↗
PubMed1999

Therapy-related malignancies following treatment of germ cell cancer.

Given the young age at which testicular cancer is treated and the excellent prognosis for patients suffering from this disease, therapy-related malignancies represent a significant problem. Therapy-related solid tumors are associated mainly with the use of radiation therapy. The risk for developing a therapy-related solid tumor is approximately 2- to 3-fold increased compared with the general population. Therapy-related leukemias are associated predominantly with chemotherapy, particularly with the use of topoisomerase-II inhibitors and alkylating agents. In general, the cumulative incidence of therapy-related leukemia is low. It is approximately 0.5% and 2% at 5 years of median follow-up for patients receiving etoposide at cumulative doses < or = 2 g/m2 and > 2 g/m2, respectively. High cumulative doses of etoposide given over a short period of time appear to be less leukemogenic than a similar dose of etoposide given over a longer period of time. There might, additionally, be a synergistic effect of cisplatin and etoposide on the induction of therapy-related leukemia. For patients who receive high-dose chemotherapy with autologous stem-cell support, the risk of therapy-related myelodysplastic syndrome and leukemia appears to be substantially lower compared with that reported in non-Hodgkin's lymphoma patients undergoing high-dose chemotherapy. The transplantation procedure itself does not appear to add to the therapy-related leukemia risk. The risk-benefit analysis in patients with testicular cancer clearly favors the use of current treatment regimens including high-dose chemotherapy. However, even the acceptably low number of therapy-related leukemias should encourage the search for equally effective but less toxic therapies.

Antineoplastic Agents↗
PubMed1999

Platinum organ toxicity and possible prevention in patients with testicular cancer.

Advances in the management of metastatic testicular cancer are attributed mainly to the introduction of cisplatin into combination chemotherapy. In parallel with the development of effective chemotherapy resulting in long-term survival for the majority of patients, possible adverse effects of treatment have been systematically investigated. Besides acute side effects of cisplatin, such as gastro-intestinal toxic effects and moderate myelosuppression, reduction in glomerular filtration rate occurs in 20% to 30% of patients despite prophylactic intensive hydration and forced diuresis. Such changes in glomerular function are essentially irreversible. Persistent effects on tubular renal function occur less commonly, but hypomagnesemia due to hypermagnesiuria is often seen. Neurotoxicity, mainly sensory peripheral neuropathy, is common during treatment but disappears in the majority of patients after its completion. However, persistent paresthesias are found in 20% to 60% of patients. A typical audiometric abnormality affecting up to 50% of patients is bilateral loss of hearing at 4 to 8 kHz. A correlation between the cumulative cisplatin dose applied and the frequency of neuro- and nephrotoxicity has been demonstrated in some studies. The administration schedule additionally appears to influence the extent of toxicity, whereby single-day infusion schedules are associated with pronounced neural and renal toxicity, possibly due to higher peak plasma levels of cisplatin. Other long-term abnormalities after treatment with cisplatin-based combination regimens are a weak predisposition to secondary malignancies, infertility and chronic vascular toxicity. Several strategies have been developed to reduce such side effects. Ongoing trials are investigating the role of the aminothiol amifostine as a nephro- and neuroprotectant.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1999

Late toxicity following curative treatment of testicular cancer.

Cisplatin appears to be the major cause for long-term toxicity in patients treated for testicular cancer. Long-term side effects consist mainly of nephrotoxicity, ototoxicity, and neurotoxicity as well as gonadal damage. Following standard-dose chemotherapy approximately 20% to 30% of patients will be affected by long-term side effects, although not all these side effects will cause an impaired quality of life. Several strategies have been or currently are being evaluated to reduce acute and long-term complications including the introduction of equally effective, but less toxic regimens, or the use of cytoprotective agents such as amifostine. Secondary acute myeloid leukemia and secondary myelodysplastic syndrome probably represent the worst possible long-term complications of cancer therapy in those patients who originally were cured of their primary testicular cancer. Therapy-related solid tumors are mainly associated with the use of radiation therapy and the risk for developing a therapy-related solid tumor is increased approximately two to three times compared to the general population. In contrast, therapy-related leukemias are predominantly associated with chemotherapy, particularly with the use of topoisomerase-II inhibitors and alkylating agents. In general, the cumulative incidence of therapy-related leukemia following treatment of germ cell cancer is low. It is approximately 0.5% and 2% at 5 years of median follow-up for patients receiving etoposide at cumulative doses< or = 2 g/m(2) and >2 g/m(2), respectively. The risk-benefit analysis in patients with testicular cancer clearly favors the use of current treatment regimens including high-dose chemotherapy. However, even the acceptably low number of therapy-related long-term complications should encourage the search for equally effective but less toxic therapies. This review will highlight important available data about therapy-related toxicity and particularly, therapy-related malignancies following cisplatin-etoposide-based chemotherapy.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1999

Future prospects in the chemotherapy of metastatic nonseminomatous testicular germ-cell cancer.

The current aims of chemotherapy in metastatic testicular cancer are to reduce treatment-related toxicity in patients with "good-prognosis" metastatic disease without compromising the efficacy and to improve treatment results in "poor-prognosis" patients according to the IGCCCG classification by the use of more dose-intensive regimens. Three cycles of PEB chemotherapy, consisting of cisplatin, etoposide, and bleomycin, remain the standard treatment for good-prognosis patients despite a number of randomized studies trying to avoid the toxicity of bleomycin or to abandon cisplatin-associated side effects by substitution with the less toxic analogue carboplatin. In patients with intermediate- and poor-prognosis criteria, four cycles of PEB given at 3-weekly intervals are considered routine treatment. The role of high-dose chemotherapy with peripheral blood stem-cell (PBSC) transplantation (HDCT) is currently being investigated for patients who initially present with poor-prognosis metastatic disease and for patients with relapse after previous chemotherapy. Favorable results with long-term survival rates of approximately 75% have been achieved with up-front sequential HDCT in a phase I-II trial of the German Testicular Cancer Study Group (GTCSG) in such patients. A randomized phase III trial comparing conventional dose chemotherapy (4x PEB) with HDCT (2x PEB + 2x HD-CEC) was initiated as a United States intergroup trial in 1996. In patients with relapsed disease, conventional salvage chemotherapy results in only an approximately 20% long-term survival rate. Particularly, primary mediastinal disease and chemotherapy refractoriness represent variables associated with a very poor outcome. HDCT is also employed in relapsed patients to improve the long-term outcome. Long-term toxicity of treatment has become an important issue due to the large group of patients with metastatic disease now being cured with modern treatment strategies. The cumulative dose of cisplatin applied has been identified as a major risk factor for the development of many types of late toxicity. Despite the major advances made in the last 20 years, evaluation of the role of HDCT in both first-line and salvage treatment, investigation of new cytotoxic agents in refractory patients, and assessment of the long-term toxicities are major tasks that remain to be addressed in controlled clinical trials.

Antineoplastic Agents↗
PubMed1999

Long-term effects on sexual function and fertility after treatment of testicular cancer.

This retrospective study evaluates the types and incidences of sexual disturbances and fertility distress in patients cured from testicular cancer and examines whether there is an effect resulting from different treatment modalities. A self-reported questionnaire was sent to 124 randomly selected patients who were treated at Hanover University Medical School between 1970 and 1993. Ninety-eight patients were included in the study, representing a response rate of 78%. All patients had been in complete remission (CR) for at least 24 months. The median age at diagnosis was 28 years (range 17-44). The median follow-up at the time of study was 12.0 years (range 2.8-25.6). Twenty patients (20%) had been treated for seminomatous and 78 patients (80%) for non-seminomatous germ cell tumours. Treatment included surveillance (7%), primary retroperitoneal lymph node dissection (RPLND) (13%), chemotherapy (CT) (33%), CT + secondary resection of residual retroperitoneal tumour mass (SRRTM) (43%) and infradiaphragmatic radiotherapy (4%). Patients receiving two treatment modalities (CT+SRRTM) reported more frequent an unfulfilled wish for children. Inability of ejaculation was clearly associated with RPLND and SRRTM. Subjective aspects of sexuality, like loss of sexual drive and reduced erectile potential, occurred only in a minority of patients after treatment. No abnormalities were observed concerning the course of pregnancies of partners. In conclusion, sexual dysfunction and infertility are common long-lasting sequelae in testicular cancer survivors affecting approximately 20% of patients. The relative risk for infertility appeared to be elevated for patients treated with the combination of CT+SRRTM. Twenty-one of 40 patients were able to fulfil their wish for children, and no congenital abnormalities were observed in these children.

Adolescent↗
PubMed1999

Phase II study of oral trofosfamide as palliative therapy in pretreated patients with metastatic soft-tissue sarcoma.

This phase II study investigated the activity of continuously administered oral trofosfamide in chemotherapy-pretreated patients with metastatic soft-tissue sarcoma (STS). Trosfosfamide is an oxazaphosphorine with ifosfamide as the predominant metabolite. Eighteen patients with a median age of 60 years were treated with trofosfamide given as continuous oral treatment. Starting dose was 300 mg/day for 7 days and subsequently 150 mg/day. All patients had previously received at least one chemotherapy regimen including doxorubicin and ifosfamide. Three patients achieved partial responses (18%) and nine a disease stabilization (53%) for an overall response rate of 18% (95% CI: 0.5-35%). Median progression-free interval was 4 months (0-17 months) and median overall survival was 10 months (4-39+) months. Toxicity was generally mild. Only one WHO grade III nausea, but no other non-hematologic WHO grade III/IV toxicity occurred. Leukopenia WHO grade III/IV was observed in four patients (22%). No thrombocytopenia <50,000/microl and no neutropenic infection was seen. Continuously administered oral trofosfamide is a well-tolerated palliative treatment in anthracycline/oxazaphosphorin-pretreated patients with advanced STS achieving responses and/or disease stabilization in up to 70% of patients.

Administration, Oral↗
PubMed1999

Mitomycin C continuous infusion as salvage chemotherapy in pretreated patients with advanced gastric cancer.

UNLABELLED: Our purpose was to evaluate the safety and therapeutic activity of continuously infused mitomycin C in patients with recurring or progressive metastatic gastric cancer following first-line chemotherapy. Patients were treated with mitomycin C 20 mg/m2 i.v. over a time period of 120 h followed by a 3-week rest period. All patients received prednisone 50 mg p.o. prophylactically for 5 days to prevent hemolytic uremic syndrome and pulmonary side effects. Twenty-two consecutively enrolled patients were assessable for toxicity and 20 for response evaluation completing at least one full course of chemotherapy (two patients evaluable but not measurable). PATIENT CHARACTERISTICS: median age: 63 years (39-76); Sex (M/ F): 13/9; median Karnofsky status: 70% (50-100%); resection of primary tumor n = 12 (55%); sites of metastases: liver n = 17 (77%), locally advanced n = 10 (45%), peritoneum n = 13 (59%), lungs n=5 (23%), bone n=3 (14%) and lymph nodes n=14 (64%). Previous chemotherapy regimens: bolus 5-FU/folinic acid n=6 (27%), ELF n=4 (18%), EAP n=3 (14%) and continuous 5-FU/folinic acid/cisplatin/paclitaxel n=9 (41%). In 20 evaluable patients one complete and five partial remissions were observed; overall response rate 30.0% [95% confidence interval (CI): 9.1-50.9%] with a median response duration of 2.1 months (range: 2-6). The median survival was 3.6 months (95% CI: 2.1-6.0) resulting in a 6-month survival rate of 30% since start of mitomycin C. WHO grade III/IV mucositis, diarrhea and fever/infection occurred in 9% of patients each. Cumulative thrombo- and leukocytopenia (WHO grade II/IV) were observed in four and two patients, respectively. Treatment had to be stopped early in two patients. No severe renal dysfunction, pulmonary toxicity or evidence of hemolytic uremic syndrome was observed. Fatigue during the 120 h infusion of mitomycin C was common (11 of 22 patients). We conclude that continuous infusion of mitomycin C is feasible on an outpatient basis, revealing an acceptable toxicity. Mitomycin C demonstrates single-agent activity in pretreated gastric cancer, but has only limited efficacy following cisplatin/paclitaxel-based first-line chemotherapy.

Adult↗
PubMed1999

First-line high-dose chemotherapy compared with standard-dose PEB/VIP chemotherapy in patients with advanced germ cell tumors: A multivariate and matched-pair analysis.

PURPOSE: To compare first-line high-dose chemotherapy (HD-CT) with autologous blood stem-cell transplantation to standard-dose chemotherapy (SD-CT) in male patients with advanced germ cell tumors (GCTs), a matched-pair analysis was performed within a homogenous group of patients classified as having either Indiana advanced disease or a poor prognosis according to International Germ Cell Cancer Consensus Group (IGCCCG) criteria. PATIENTS AND METHODS: A multivariate analysis was performed that included 147 consecutive patients who had received sequential high-dose cisplatin, etoposide, and ifosfamide (VIP) therapy (HD-CT) in a German multicenter trial between 1993 and 1997 and 309 patients who had been treated with standard-dose cisplatin, etoposide, and bleomycin (PEB) or VIP chemotherapy (SD-CT) within two randomized trials at Indiana University between 1984 and 1992. RESULTS: Multivariate analysis demonstrated HD-CT to be significantly superior to SD-CT when adjustments were made for prognostic factors (P =.021). Primary tumor site (mediastinal v retroperitoneal/gonadal, P =.035) and presence of visceral metastases (P =.0004) were shown to be significant prognostic factors for overall survival. On the basis of these factors, as well as on tumor marker levels (good, intermediate, or poor, according to IGCCCG criteria), 146 of 147 HD-CT patients were fully matched to an SD-CT patient. Median follow-up was 21 months (range, 0 to 70 months) for the HD-CT patients and 22 months (range, 0 to 90 months) for the SD-CT patients. Two-year progression-free survival (75% v 59%) and overall survival (82% v 71%) were significantly prolonged in HD-CT patients (P =.0056 and P =.0184, respectively). CONCLUSION: The results indicate that first-line HD-CT in patients with poor-prognosis GCT may result in a significant improvement of progression-free and overall survival as compared with SD-CT. Salvage HD-CT seems not to compensate this survival advantage.

Antineoplastic Combined Chemotherapy Protocols↗