Chemotherapy For Germ Cell Tumors Research Articles

Long-term complications of chemotherapy for germ cell tumours.

Testicular cancer is the most common solid tumour among young males aged 15-35 years. Cisplatin-based combination chemotherapy has changed the outlook of this disease. Disseminated testicular cancer, once uniformly fatal, now has a cure rate of more than 80% with combination chemotherapy. Systematic randomised trials have shown that cisplatin, etoposide and bleomycin (PEB) combination chemotherapy remains the mainstay of treatment. While there is a high cure rate with chemotherapy in patients with this disease, some long-term complications from chemotherapy have now been recognised, including secondary leukaemia, therapy-related solid tumours, nephrotoxicity, neurotoxicity, pulmonary toxicity, vascular toxicity and infertility. Etoposide, a DNA topoisomerase II inhibitor, is a significant risk factor for developing leukaemia; the risk appears to be correlated with the total dose given. Patients receiving cisplatin-based combination chemotherapy for testicular cancer also appear to have a higher relative risk for developing second non-germ cell malignancies; the greatest risks for therapy-related solid tumours were seen with a combination of radiation therapy plus chemotherapy. Long-term vascular toxicities associated with chemotherapy include Raynaud's phenomenon, acute myocardial infarction and cerebrovascular events. Bleomycin is thought to be the most important drug in the pathogenesis of Raynaud's phenomenon, while cisplatin is the most likely agent involved in myocardial infarction. Peripheral neuropathy is the most common form of neurotoxicity observed with cisplatin-based chemotherapy. Risk factors for the development of neural damage include a high cumulative dose of cisplatin, the use of vinblastine and the concomitant development of Raynaud's phenomenon. Cisplatin is also well known to cause significant nephrotoxicity. Approximately 25% of patients present with azoospermia after undergoing combination chemotherapy with a follow up of 2-5 years. Physician awareness of complications associated with chemotherapy is vital to maximise efficacy, minimise toxicity, and preserve quality of life after treatment. Sperm cryopreservation should be considered for patients who desire children. Close monitoring during therapy allows for the early diagnosis of complications, and close follow up of patients after the completion of therapy is necessary to monitor for relapse and development of long-term complications such as myelodysplastic syndrome and leukaemia. Despite these complications, given the potential for cure rates in this young group of patients, the benefits far outweigh the risks.

Risk-Adapted Chemotherapy of Germ Cell Tumors with Carboplatin, Etoposide and Bleomycin for Low-Risk and Cisplatin, Etoposide and Ifosfamide for High-Risk Patients

The prognosis of germ cell tumors treated with chemotherapy depends on the presence of nonseminomatous tumor, clinical parameters based on the tumor volume and site, as well as on the level of the tumor markers AFP, βHCG and LDH. We report here on the results of a risk-adapted approach to the chemotherapy of germ cell tumors. Patients with low-risk tumors, defined as seminomatous disease and/or nonseminomatous disease with a tumor mass <10 cm, less than 20 lung metastases, no liver, bone, or CNS metastases, and levels of AFP <1,000 IU/ml and βHCG <10,000 IU/l, were to receive 4 cycles of carboplatin 400 mg/m² i.v. day 1, etoposide 120 mg/m² i.v. days 1–3 and bleomycin 30 IU i.v. days 1, 8 and 15 during the first 3 cycles (CEB₉₀). Patients with high-risk disease were to receive 4 cycles of ifosfamide 1,500 mg/m² continuous infusion on days 1–4 together with mesna 1,200 mg/m² days 1–5, cisplatin 20 mg/m² i.v. days 1–5 and etoposide 100 mg/m² i.v. days 1–5 (VIP). Of the 60 patients treated with this risk-adapted approach, 51 had low-risk and 9 had high-risk disease. Forty-five of 51 patiens treated with CEB₉₀ achieved complete remission (CR), 4 achieved partial remission with marker negativity. Four patients with CR relapsed between 4 to 8 months after the start of chemotherapy. Of the 6 patients failing CEB₉₀, 3 were treated successfully with surgery or further chemotherapy. With a median follow-up of 52 months, the estimated cause-specific 3-year survival is 93% (95% confidence interval, CI, 80–98%). Seven of 9 high-risk patients treated with VIP achieved a CR and 1 patient relapsed. All 3 patients failing VIP had successful salvage therapy. With a medium follow-up of 63 months all patients remain alive and free of disease. Forty-six patients receiving CEB₉₀ were retrospectively classified to be in the good prognosis group according to the international germ cell consensus classification. Their estimated 3-year survival was 95% (CI 81–99%). We thus confirm that CEB₉₀ is a well-tolerated outpatient regimen with good results in good prognosis germ cell tumors. Bleomycin at a cumulative dose of 270 U might contribute substantially to the inferior effect of carboplatin as compared to cisplatin. However, in view of the results of randomized studies favoring cisplatin over carboplatin, it is not recommended to use this regimen outside a clinical trial.

The growing teratoma syndrome: results of therapy and long-term follow-up of 33 patients

Growing teratoma syndrome (GTS) is defined as an increase in tumour size during or after chemotherapy for germ cell tumour (GCT), and only mature teratoma at histological analysis of the resected tumour specimen. Between 1985 and 1997, 30 male patients fulfilling GTS criteria were included in the present study. 3 female patients were also included but analysed separately. A mature teratoma component was found in 86% of the primary GCT. 3 male patients (10%) had a complication at diagnosis of GTS. One male patient (4%) having undergone complete resection ( n=24) had a recurrent GTS, compared with all but 1 patient (83%) in whom resection was partial ( n=6) ( P<0.001). 2 (8%) and 3 (50%) male patients treated with complete and partial resection subsequently developed a malignant NSGCT respectively ( P=0.01). 2 female patients treated with partial resection presented a recurrent GTS. One of them died of this recurrent GTS. GTS is an entity in its own right with respect to complications and the natural history of the disease. Complete surgical resection is the treatment of choice for GTS.

Malignant germ cell tumors of the ovary: Pregnancy considerations

Objective: To study the pregnancy association and malignant germ cell tumors of the ovary with regard to its effects on tumor prognosis. Study Design:: Seventy-five patients with malignant germ cell tumors of the ovary treated at the King Faisal Specialist Hospital-Research Center (KFSH–RC) Riyadh, Kingdom of Saudi Arabia between January 1976 and December 1992, were reviewed. Data was retrieved from the medical records and the database of ovarian tumor pathology. Patients with tumor/pregnancy association were identified and correlation with obstetrical outcome and tumor prognosis analyzed. Patients who conceived after treatment were identified and their reproductive outcome described. Results: Malignant germ cell tumor was associated with pregnancy in a group of ten patients. Possible tumor effects upon pregnancy in this group included operative delivery by caesarean section ( n=3), mid-trimester termination ( n=2), spontaneous abortion ( n=1). Four patients had normal vaginal birth with no apparent tumor effects upon pregnancy. Pregnancy did not seem to influence the tumor prognosis of pure dysgerminoma ( n=6), however, two patients with non-dysgerminomatous germ cell tumor (one endodermal sinus tumor and one immature teratoma) died of rapidly progressive disease during the second trimester. Two patients with advanced (stage IIIC) disease concurrent with pregnancy (one pure dysgerminoma and one mixed germ cell tumor), had normal fetal outcomes and achieved long-term survival. Amongst the 22 patients who planned to conceive after conservative surgery, with or without post-operative adjuvant chemotherapy, 12 conceived (12/22) and achieved a total of 20 pregnancies. Their outcomes included normal births ( n=18) including one set of twins and hydatidiform moles ( n=2). Conclusions: Our findings suggest that, (1) The association of pure dysgerminoma and pregnancy did not adversely affect the tumor prognosis or fetal outcome. However, the question remains as to whether pregnancy worsened the prognosis of non-dysgerminomatous germ cell tumors. (2) Recent platinum-based regimens of multiagent chemotherapy for germ cell tumors did not seem to affect fertility potential.

Results of treatment after relapse from high-dose chemotherapy in germ cell tumors.

To identify therapy-related or patient-related characteristics that predict response and long-term survival after failure of high-dose chemotherapy (HDCT) for germ cell tumors (GCT). Between 1986 and 1997, 101 GCT patients relapsed after high-dose carboplatin and etoposide (VP-16) at Indiana University (Indianapolis, IN). Median time to relapse was 10 months (range, 1 to 17 months). HDCT was the first salvage treatment in 29 patients and second or later salvage treatment in 72 patients. Fifty-four of 101 patients received post-HDCT treatment. Of these, 47 received chemotherapy, alone (n = 35) or in combination with surgery (n = 12). Seven patients underwent surgery alone. There were only 12 objective responses (three complete and nine partial responses) for 66 chemotherapy regimens given to 47 patients, for an overall response rate of 18.2%. Fifteen patients received platinum-based chemotherapy, with only one objective response. Chemotherapy was discontinued in 17% of cases because of toxicity. A longer interval between HDCT and post-HDCT treatment was the only variable that was associated with response. Five patients (4.9%) are disease-free at 30, 53, 57, 85, and 93 months after relapse. Of these, three responded to oral VP-16 and underwent resection of residual mediastinal, retroperitoneal, and inguinal cancer, respectively. One had resection of residual mediastinal yolk sac tumor, followed by oral VP-16. One relapsed with teratoma and received thoracoabdominal resection without chemotherapy. Patients who experience disease progression after HDCT often receive further chemotherapy and/or surgery. Chemotherapy resulted in a response rate of less than 20%, with only three complete responses. All of the long-term survivors (4.9%) had surgery as a component of their post-HDCT regimen.

125I-labelled human chorionic gonadotrophin (hCG) as an elimination marker in the evaluation of hCG decline during chemotherapy in patients with testicular cancer.

The rate of reduction in the concentration of serum human chorionic gonadotrophin (hCG) following chemotherapy for germ cell tumours may follow a complex pattern, with longer apparent half-life during later stages of chemotherapy, even in patients treated successfully. The commonly used half-life of less than 3 days for hCG to monitor the effect of chemotherapy in patients with germ cell tumours of the testis may represent too simple a model. 125I-labelled hCG was injected intravenously in 27 patients with germ cell tumours and elevated hCG during chemotherapy. The plasma radioactivity and hCG concentrations were followed. During chemotherapy, the plasma disappearance of hCG showed a biphasic pattern, with an initial fast and a later slow component in all patients. Using the steep part of the hCG plasma disappearance curve, five patients who achieved long-term remission had half-lives longer than 3 days (3.6–6.8 days), whereas four out of five patients not achieving long-term remission had half-lives shorter than 3 days. After the third treatment cycle, eight patients who achieved long-term remission had hCG half-lives longer than 3 days (7.4–17.0 days). In these patients, the plasma disappearance of [125I]hCG was equivalent to that of hCG. Thus, the slow decline of hCG represented a slow plasma disappearance rather than a hCG production from vital tumour cells and could, consequently, not be used to select patients for additional or intensified chemotherapy. The concept of a fixed half-life for plasma hCG during treatment of hCG-producing germ cell tumours is inappropriate and should be revised. Difficulties in interpreting a slow decline of hCG may be overcome by comparing the plasma disappearance of total hCG with the plasma disappearance of [125I]hCG. © 1999 Cancer Research Campaign

High-dose chemotherapy in germ cell tumours: a large single centre experience

High-dose chemotherapy (HDCT) has evolved as a strategy to improve the treatment outcome in patients with relapsed and/or refractory germ cell tumours. Between August 1989 and September 1995, 150 consecutive patients with relapsed and/or refractory germ cell tumours were treated with conventional-dose salvage chemotherapy followed by one cycle of HDCT with carboplatin 1500–2000 mg/m 2, etoposide 1200–2400 mg/m 2 and ifosfamide 0–10 g/m 2 and were retrospectively analysed. With a median follow-up time of 55 months (range 21–88 months) 51/150 (34%) patients are alive and disease free. The projected event-free and overall survival are 29% (confidence interval 22–37%) and 39% (confidence interval 31–47%) respectively. The relevance of prognostic variables for long-term survival after HDCT were prospectively confirmed. Persisting toxicities occurred in approximately one third of the long-term survivors. Treatment intensification with HDCT resulted in a significant proportion of long-term survivors in patients with relapsed and/or refractory germ cell tumours. Trials to prospectively evaluate HDCT as an early intervention in these patients seem justified.

Chemotherapy for germ cell tumors relapsing after high-dose chemotherapy and stem cell support: A retrospective multicenter study of the Austrian Study Group on Urologic Oncology

In most patients with advanced refractory germ cell tumors undergoing high-dose chemotherapy with stem cell support (HDCT) the disease progresses after HDCT. This study was designed to shed light on the unestablished role of post-HDCT chemotherapy. In a retrospective multicenter study data of 47 evaluable patients from nine centers subjected to post-HDCT chemotherapy for progression of their germ cell tumors were collected in a questionnaire survey and analyzed for treatment response and survival. Of 191 patients pretreated by HDCT, 48 (25%) were subjected to post-HDCT chemotherapy for disease progression. Remission was achieved in 17 (36%) and marker-negative remission in eight (17%). The median survival time was 26 weeks, 65 weeks for responders and 13 weeks for non-responders. Only one of 47 evaluable patients achieved sustained complete remission. Remissions significantly correlated with the post-HDCT interval, the use of ifosfamide and the combination regimens of cisplatin + etoposide i.v. or ifosfamide and of paclitaxel + ifosfamide or cisplatin. On univariate analysis a longer post-HDCT interval, the use of cisplatin, paclitaxel and ifosfamide and the combined use of paclitaxel + ifosfamide and/or cisplatin significantly improved the chances of survival. On multivariate analysis only treatment with paclitaxel and ifosfamide retained independent prognostic significance for survival. One third of the patients considered to be candidates for further chemotherapy once progressive after HDCT went into remission with a gain in survival time. Sustained remissions may occur, but are rarely seen. Paclitaxel and ifosfamide appear to be the most effective drugs in these heavily pretreated patients.

Late relapse of germ cell tumors after cisplatin-based chemotherapy

Sparse data are available with regard to the incidence, clinical characteristics, therapeutic management and prognosis of male patients with germ cell tumors, who relapse more than two years after completion of cisplatin-based chemotherapy. A review of 530 patients treated at two institutions from 1978 to April 1994 was conducted. Twenty-five cases of late relapse were identified. Cumulative risk of late relapse was calculated according to the Kaplan-Meier method. 418 of 523 patients (80%) who received their first-line treatment at our institutions were relapse-free at two years. Among these 418 patients 18 cases (4.3%) developed a late relapse. The cumulative risk of late relapse was 1.1% at five years and 4.0% at ten years excluding patients with prior early relapses who carried risks of 9.4% and 29%, respectively (P < 0.0001). No case of late relapse was observed among patients receiving adjuvant chemotherapy. The risk of late relapse was lower in patients with good-risk non-seminomatous germ cell tumors than in poor-risk patients according to Medical Research Council criteria (P < 0.01). Seven further patients were referred from other institutions for treatment of late relapse. At a median follow-up of 38 months (range, 3 to 121) after treatment of late relapse 9 of 25 patients (36%) are continuously disease-free. Six of these nine patients had surgical resection of carcinoma or teratoma as a component of their therapy. The incidence of late relapse after cisplatin-based chemotherapy of germ cell tumors is related to initial tumor burden and is somewhat higher than previously expected. Chemotherapy seems to have only minor curative potential, but localized resectable disease can be cured by surgery. Annual follow-up evaluations allow to detect the majority of late relapses at an asymptomatic stage and should be extended throughout the patient's life.

Simultaneous retroperitoneal, thoracic, and cervical resection of postchemotherapy residual masses in patients with metastatic nonseminomatous germ cell tumors of the testis.

We report our experience with simultaneous resection of residual masses above and below the diaphragm in patients with metastatic nomseminomatous germ cell tumor (NSGCT) of the testis. Twenty-four patients underwent simultaneous resection of residual postchemotherapy masses in the retroperitoneum and chest, including three who also had radical neck dissection. All had been heavily pretreated with chemotherapy and five had undergone previous retroperitoneal lymph node dissections (RPLNDs). The combined procedure was performed with no mortality and low morbidity. The median length of the procedure was 5 hours 45 minutes, median blood loss 500 mL, and median length of hospital stay 9 days. Complications included one patient with chylous ascites and one with a prolonged air leak, both of which resolved with conservative management. Eighteen patients had similar pathologic findings in all sites: 13 with necrosis only and five with teratoma only. Six patients had discordant pathology in the abdomen and chest, including one with viable tumor in the chest only and two with viable tumor in the abdomen only. The overall actuarial 5-year survival rate for all patients was 79%. Simultaneous resection of neck, chest, and abdominal residual masses after chemotherapy for germ cell tumors is both a feasible and safe alternative to staged excision in selected patients who require surgical intervention at multiple sites and fulfills the objective of rendering patients disease-free in a single operative procedure.

MYOCARDIAL-INFARCTION AFTER ADJUVANT CHEMOTHERAPY FOR RESECTED STAGE-II NONSEMINOMATOUS TESTICULAR CANCER

Although acute toxicity of cisplatin-based chemotherapy of germ cell tumors is considerable, major vascular complications have been reported infrequently. This report describes the case of a 36-year-old man developing myocardial infarction after the first cycle of adjuvant cisplatin-based chemotherapy for resected stage II testicular cancer. A close temporal association between the administration of chemotherapy and the vascular event suggests a cause and effect relationship. A drug-induced endothelial cell damage may be an important pathogenetic factor. Although reports on vascular accidents following treatment of testicular cancer raise concern with regard to the safety of chemotherapy, at present the very low incidence of such complications should not enter into therapeutic decisions.

Prognostic significance of early serum tumor marker half-life in metastatic testicular teratoma.

To determine whether the initial regression rates of serum tumor marker concentration (alpha-fetoprotein [AFP] and beta-human chorionic gonadotrophin [HCG]) were important prognostic factors after chemotherapy for germ cell tumors. The analysis was confined to patients with at least two precise marker assay results between days 7 and 22 from start of platinum-based combination chemotherapy, with at least 7 days between markers. One hundred eighty-three patients were eligible and marker half-life (MHL) was evaluated for AFP in 142 and for HCG in 111 cases. MHL was calculated from the following formula: MHL = Ln1/2/G, where G was the gradient of the marker slope on a plot of Ln marker concentration versus time. MHL was regarded as prolonged if more than 3 days for HCG or more than 7 days for AFP. The median AFP MHL was 6 days (range, 2.7 to 237) and the median HCG MHL was 2.6 days (range, 1.7 to 37.5). Forty-nine of 142 patients (35%) had a prolonged AFP MHL; 39 of 111 patients (35%) had a prolonged HCG-MHL. A prolonged MHL did not identify relapse after front-line chemotherapy. The positive predictive value of MHL tests in identifying patients who progressed after front-line therapy was 18% for HCG, 20% for AFP, and 18% for either marker. A prolonged MHL did indicate a higher risk of mortality (hazards ratio [HR], 2.4; P = .016), but again the positive predictive value of this test was only 23%. Early evaluation of MHL by this method does not predict patients at higher risk of progression after front-line chemotherapy, and also is a poor guide to long-term prognosis.

Chemotherapy for germ cell tumours: Prophylactic ciprofloxacin reduces the incidence of neutropenic fever

To assess the value of prophylactic cipro-floxacin in reducing the incidence of neutropenic fever in men receiving intensive chemotherapy for germ cell tumours, we reviewed the case notes of 88 consecutive patients treated between January 1986 and December 1992. Nadir blood counts were performed in all patients on day 14. From 1989, prophylactic ciprofloxacin 250 mg b.d. was started when the neutrophil count was less than 1 × 10 9/l and then prescribed for all subsequent courses of chemotherapy from day 7 to day 21. In total, 88 men received 429 courses of chemotherapy. Prophylactic ciprofloxacin was prescribed for 168 courses. This was associated with a trend towards reducing the risk of admission per course of chemotherapy from 8% (20/261) to 4% (6/168) ( P = 0.08). WHO grade ¾ neutropenia (<1 × 10 9/l) was documented for 240 (56%) courses of chemotherapy. The incidence of fever in these patients was significantly reduced from 15% (20/131) to 5% (6/109) ( P = 0.02) with prophylactic ciprofloxacin. Two patients, one of whom had received prophylactic ciprofloxacin, died of chest infection confirmed on post-mortem. The results of this non-randomized, retrospective study suggest that prophylactic ciprofloxacin 250 mg b.d. is effective in reducing the incidence of fever complicating neutropenia during chemotherapy for germ cell tumours. To be cost effective, it should be given only to neutropenic patients.

Long-term results of two VAB-like regimens (vinblastine + actinomycin-D + bleomycin + cyclophosphamide + cisplatin) in malignant germ cell tumours of the ovary

21 patients with malignant germ cell tumours of the ovary were treated with two chemotherapy regimens including vinblastine, actinomycin-D, bleomycin, cyclophosphamide and cisplatin. Chemotherapy was delivered as primary postoperative therapy in 15 patients and for recurrent disease in 6 patients. 3 of 4 patients with pure dysgerminomas and 10 of 17 patients with non-dysgerminomatous tumours are alive without evidence of disease. The overall progression-free survival is 62% (95% confidence interval 45–77) with a median follow-up of 7 years. Two toxic deaths were observed. Less toxicity and better efficacy favour etoposide- and cisplatin-based regimens as standard chemotherapy for germ cell tumours of the ovary.

Acute and Late Vascular Complications Following Chemotherapy for Germ Cell Tumors

Side effects of cisplatin-based chemotherapy for germ cell tumors include myelosup-pression, nephro-, neuro- and ototoxicity. These side effects as well as the pulmonary toxicity of bleomycin are dose-dependent. On the contrary, chemotherapy-associated vascular complications are unpredictable. Whereas Raynaud’s phenomenon is observed in a considerable proportion of patients, myocardial infarction, stroke, and pulmonary embolism appear to occur infrequently. The fact that some patients have been in complete remission at the time of myocardial infarction or cerebrovascular accident argues against a tumor-induced complication and is an argument in favor of a possible causative role of chemotherapy. An alteration of the clotting system and vascular smooth muscle tone as well as an endothelial cell damage are discussed to be pathogenetic mechanisms. Pulmonary embolism, on the contrary, seems to be more frequently associated with inferior vena caval obstruction by tumor masses. Presently there is a debate whether, apart from rare acute vascular events, chemotherapy for testicular cancer leads to a long-term alteration of lipid profile and thereby eventually increases cardiovascular risk.

Infections in patients treated with high-dose chemotherapy for germ cell tumours

25 patients with disseminated germ cell tumours were treated with high-dose cisplatin and etoposide (40 mg/m 2 and 200 mg/m 2 daily × five, respectively) leading to severe myelosuppression. A comprehensive study was undertaken in order to identify and describe the bacterial, viral and fungal infections in this group of patients. Fever (> 38.5°C) and leucopenia (white blood cell count < 1.0 × 10 9/l) were observed in 61 of 90 treatment cycles (68%). A microbiological aetiology compatible with the clinical manifestations of infection could be identified in 33 of the 61 febrile episodes (54%). Bacteraemia occurred in 14 episodes in 12 patients. Eight episodes (57%) involved gram-positive aerobic bacteria.

Chemotherapy of Germ Cell Tumors: Current Status and Future Directions

Chemotherapy of Germ Cell Tumors: Current Status and Future Directions

Hypercholesterolemia after chemotherapy for testis cancer.

The study was designed to determine prospectively the prevalence of fasting serum lipid abnormalities in patients who were treated with cisplatin-based chemotherapy for germ cell tumors. We unexpectedly had demonstrated hypercholesterolemia in 20 of 30 nonfasting patients in a prior study of long-term toxicity of chemotherapy for germ cell tumors. The present study was designed to explore this phenomenon further. Seventeen unselected patients with biopsy-proven germ cell tumors, who underwent cisplatin-based chemotherapy and who had no prior history of cardiac disease nor known hypercholesterolemia, were studied. In addition to the standard staging tests, blood was drawn for a pretreatment fasting lipid screen, which included cholesterol, triglycerides, high-density lipoprotein (HDL) cholesterol, and apolipoproteins A1, B, and (a). Repeat samples were drawn 24 hours after the administration of cisplatin and at intervals of 6 to 24 months after the completion of treatment. Seven of 17 patients (41%) had higher than desirable levels of total serum cholesterol and low-density lipoprotein cholesterol. Two of them had normal levels before treatment, four had preexisting hypercholesterolemia that increased further, and one patient had an elevated pretreatment level that did not alter. Absolute increases in serum cholesterol were noted in 14 of 17 patients. No consistent patterns of change beyond the reference ranges were found for other serum lipids. We have confirmed our initial observation that serum cholesterol increases in patients who received cisplatin-containing chemotherapy regimens for germ cell tumors. Further studies will be necessary to define whether other lipid abnormalities occur and the biologic significance of these findings.

Resection of residual mediastinal germ cell masses with the Cavitron ultrasonic surgical aspirator

Residual mediastinal masses after chemotherapy for germ cell tumors should be resected. Complete excision of bulky residual masses may sometimes be difficult because of problems with exposure in the region of the great vessels and important nerves. Two cases are presented in which the Cavitron ultrasonic surgical aspirator (Valleylab Inc., Surgical Systems Division, Stamford, Conn.) facilitated excision of large masses after intensive chemotherapy. We found that the collapsed pseudocapsule remaining after aspiration of tumor mass allowed early improved exposure and safer dissection from neighboring vessels and neural structures. Complete excisions were accomplished and no viable tumor was found, so that the patients were spared the immediate need for further therapy. Both had uneventful recoveries.

Treatment of advanced epithelial ovarian carcinoma in pregnancy with cisplatin-based chemotherapy

Malignant ovarian neoplasms associated with pregnancy are uncommon, and the majority of these are Stage I. While adjuvant chemotherapy for germ cell tumors during pregnancy has been reported, only one previous report exists on the use of cisplatin-based chemotherapy for epithelial ovarian carcinomas during pregnancy. A patient with Stage III cystadenocarcinoma of the ovary treated during pregnancy with five courses of dose-intensive cisplatin and cyclophosphamide is presented. No adverse fetal effects secondary to cisplatin-based chemotherapy were noted. A review of the literature is presented.