Changes in cellular immunity during chemotherapy for testicular cancer

BACKGROUND: The changes in vivo in immunocyte functions during chemotherapy that is administered in combination with granulocyte colony-stimulating factor (G-CSF) in humans have not been fully investigated. This study was designed to examine neutrophil functions and the activities of natural killer (NK) cells, during the administration of chemotherapy and G-CSF for the treatment of testicular cancer. METHODS: Seven patients with germ cell tumors at stage IIA, IIB or IIIB, who were treated with bleomycin, etoposide and cisplatin (BEP), were enrolled in the study. Numbers and activities of neutrophils and NK cells were measured at various times during and after the first course of chemotherapy. Neutrophil phagocytosis was quantitated by flow cytometry with fluorescent latex beads. Bactericidal activity was measured in terms of colony-forming units. The activity of NK cells was measured by monitoring the release of 51Cr. RESULTS: After BEP chemotherapy, CD16+ and CD56+ cell counts, and neutrophil granulocyte counts decreased while there were no significant changes in the number of lymphocytes. Phagocytosis by neutrophils was enhanced after administration of G-CSF. The activity of NK cells was severely impaired after chemotherapy and did not change after administration of G-CSF. CONCLUSIONS: After BEP chemotherapy for testicular cancer with G-CSF, neutrophil function was not at all inferior to those before treatment. Natural killer cell activity was suppressed by the BEP chemotherapy and did not change after administration of G-CSF.     

Gynecomastia following chemotherapy for testicular cancer

A 22-year-old man received 4 cycles of bleomycin, etoposide and cisplatin combination chemotherapy for clinical stage IIA embryonal cell carcinoma of the right testis. The treatment resulted in complete remission. Five months following cessation of the chemotherapy first on the left and then 2 weeks later on the right side painful gynecomastia developed. His hormonal values are all normal with no evidence of recurrence of the cancer. Gynecomastia on both sides resolved in 8 months spontaneously without any treatment. He is still in clinical remission 14 months after completion of the chemotherapy. We should be aware that gynecomastia following cytotoxic chemotherapy in a young man does not necessarily mean the return of the cancer.     

Fertility after chemotherapy for testicular cancer

Disseminated testicular cancer has largely become curable with cisplatin-based chemotherapy. The prospect of fertility after treatment is an important consideration for both patients and clinicians. While there may be an irreversible impairment of spermatogenesis at a cumulative cisplatin dose of greater than 400 mg/m2, a low sperm count does not necessarily appear to prevent fatherhood. This review summarizes currently available data on the effects of chemotherapy on male fertility and steps that can be taken to preserve fertility in this patient population.     

转移性睾丸癌的联合化疗

报告８例转移性睾丸癌病人术后联合化疗结果。７例获完全缓解，１例获部分缓解。１例治疗后２年死于肺转移，其余７例随访１６～９８个月（平均５４个月）均生存。本组结果表明转移性睾丸癌经化疗能够治愈。     

Complications of surgery and chemotherapy for testicular cancer

Testicular cancer is a malignancy for which an interdisciplinary approach offers the highest likelihood of cure. In many patients, both chemotherapy and surgery play a prominent role in their care. Although cure can be achieved in a majority of patients, the treatment can occasionally leave the patient with late sequelae. This article discusses the long-term toxicity of curative surgical or cytotoxic therapy for germ cell tumors.     

Computed tomography in evolution of testicular cancer during intensive chemotherapy.

The evolution of malignant testicular tumor to mature teratoma has been studied in 4 patients. Computed tomography has been helpful in early diagnosis of this biologic phenomenon in these patients receiving intensive chemotherapy for disseminated non-seminomatous testicular cancer. Although the potential significance of this conversion in terms of survival is not known its early recognition by computed tomography has been useful in selecting and monitoring the therapy of these patients.     

Renovascular hypertension after combination chemotherapy for testicular cancer

Chemotherapy with cis-platinum, vinblastine and bleomycin for germ cell tumors of the testis has been highly effective but it also has been associated with acute and chronic vascular damage. We report the development of hypertension in a 38-year-old man after chemotherapy that was shown to be owing to nonatherosclerotic partial occlusion of the major branches of the left renal artery. Vascular complications following combination chemotherapy for germ cell tumors are reviewed.     

Vascular and other complications of chemotherapy for testicular cancer

Summary The chronic toxicities of the drug combinations, VBP and VAB-6, which are used to cure patients with metastatic testicular cancer are not well defined. Recently, Raynaud's phenomenon has been reported to occur in 5–35% of patients treated with VBP. Other vascular complications such as renovascular hypertension, myocardial infarctions and cerebrovascular accidents have been anecdotally reported. Since patients with this disease are young, efforts to identify and eliminate chronic drug toxicities are warranted.Supported in part by American Cancer Society Junior Faculty Clinical Fellowship No. 639-A     

False-positive elevation of alpha-fetoprotein during induction chemotherapy in patients with testicular cancer

During induction chemotherapy, we experienced the false elevation of the tumor marker alpha-fetoprotein (AFP) in some disseminated testicular cancer patients. We discussed the possibility of the false elevation of the tumor marker AFP and evaluated the relationship between AFP and the markers of liver damage (GOT, GPT, LDH, etc.), the elevation of which were caused by induction chemotherapy of the VAB-6 regimen. We evaluated each variable of the eleven patients with disseminated testicular cancer who had been treated in our hospital between 1979 and 1984. The elevation of each marker of liver damage was induced by the VAB-6 regimen, immediately after the end of each induction chemotherapy but not by other induction chemotherapy regimens. A statistical study confirmed that there was a close correlation between the elevation of AFP and of the markers of liver damage, that is induced frequently by the induction chemotherapy of VAB-6 regimen.     

Lack of gonadal protection by medroxyprogesterone acetate-induced transient medical castration during chemotherapy for testicular cancer

The serum FSH levels were analysed in 24 testicular cancer patients 3 to 9 years after intensive chemotherapy. Sperm cell counts were performed in 12 patients. In all cases a temporary medical castration had been achieved during intensive chemotherapy by the use of medroxyprogesterone acetate (MPA) (500 mg daily per os). The hormone treatment was initiated on day 1 of the first chemotherapy cycle. Thirteen additional patients did not receive this hormone treatment but were treated by similar chemotherapy. The latter patients served as a control group. There was a tendency towards higher FSH levels in the MPA-treated patients than in the controls. Following treatment, serum testosterone was significantly lower in patients who had received MPA during their intensive chemotherapy than in the controls. There was no difference between the groups with regard to recovery of sperm cell production after chemotherapy. An MPA-induced medical castration during intensive chemotherapy in testicular cancer patients is ineffective in protecting the remaining testis against treatment-induced damage to spermatogenesis, at least if hormone treatment is started simultaneously with chemotherapy.     

Fatal basilar artery thrombosis after chemotherapy for testicular cancer

We report a 31-year-old patient with a pT3N2M1 seminoma who received cisplatin-based chemotherapy. During the second course of chemotherapy, the patient suffered a thrombosis of the basilar artery. He died 14 h after hospital admission. Cerebrovascular events related to cisplatin-based chemotherapy are rare, however, these potentially fatal events should be kept in mind when treating patients with testicular cancer.     

Leydig cell function in patients with testicular cancer during and after chemotherapy

In two groups of patients with disseminated testicular carcinoma the effect of combination chemotherapy on the pituitary-gonadal axis was evaluated, after unilateral orchiectomy: The two groups comprised 15 patients without hCG-producing metastases (group A), and 14 patients with hCG-producing metastases (group B). Seven patients who had received no chemotherapy were studied one year after unilateral orchiectomy as a control group (group C). In group A, serum levels of testosterone and oestradiol increased during chemotherapy, as did the levels of LH and FSH. The serum LH and FSH response to LHRH was increased following chemotherapy, whereas the serum testosterone increase after hCG stimulation remained unchanged. A rise of 316% in SHBG binding capacity was found after chemotherapy. This presumably accounted for the elevated steroid levels in the presence of high gonadotrophin levels, but unaltered Leydig cell response. The elevated serum levels of testosterone and oestradiol and the suppressed serum FSH levels normalized during disappearance of ectopic hCG production in group B patients. Leydig cell refractoriness to hCG and the FSH response to LHRH also reverted to normal. After chemotherapy, FSH, but not LH levels exceeded those of group C patients, presumably as a result of the azoospermia induced by chemotherapy. The hormonal changes associated with chemotherapy are best explained by an increase in serum binding proteins, notably SHBG.     

Acute myocardial infarction during combined chemotherapy with bleomycin, etoposide and cisplatin for testicular cancer

We report a case of acute myocardial infarction during combined chemotherapy with bleomycin, etoposide and cisplatin for testicular cancer. A 30-year-old smoker without any history of ischemic heart disease complained of sudden chest pain on the ninth day of his third course of chemotherapy. An electrocardiogram showed ST segment elevation in II, III and aVF. Emergency coronary angiography revealed total occlusion of the right coronary artery by a thrombus, which was removed by coronary atherectomy.     

Results of chemotherapy and salvage surgery for advanced testicular cancer

Since 1980, 73 patients with advanced testicular cancer have been treated with chemotherapy and 43 patients received post-chemotherapy (salvage) surgery. The median age of all patients was 31 years old, ranging from 17 to 63 years. The histology of the primary testicular tumor was pure seminoma in 23 patients and non-seminoma in 50 patients. According to the Japan Urological Association classification, 38 patients were classified as stage II and 35 patients as stage III. As first-line chamotherapy, 52 patients were treated with PVB regimen (cisplatin, vinblastin, bleomycin), 16 patients with PEB (cisplatin, etoposide, bleomycin) and 5 patients with VAB-6 (vinblastine, actinomycin-D, bleomycin, cisplatin, cyclophosphamide). Thirty (41%) of the 73 patients achieved a complete response (CR) with chemotherapy alone and 63 (86%) achieved no evidence of disease (NED) with salvage treatment. As second-line chemotherapy, 16 patients were treated with PE (cisplatin, etoposide), or VIP (etoposide, ifosfamide, cisplatin) or VeIP (vinblastine, ifosfamide, cisplatin). One of the 16 patients achieved CR and 11 (69%) patients achieved NED. As salvage surgery, retroperitoneal lymphnode dissection (RPLND) was performed in 22 patients, RPLND with thoracotomy in 7 cases and thoracotomy alone in 4 cases. Necrosis was found in surgical specimens of 24 (56%) patients, mature teratoma in 6 (14%) and residual cancer in 13 (30%). Ninety-six percent and 100% of the patients with necrosis and mature teratoma survived with NED, respectively, but only 54% of the patients with residual carcinoma survived despite further treatment. Residual cancer was still found in 8 of the 32 (25%) marker normalized cases. Residual cancer could not reliably be predicted or discriminated from necrosis or mature teratoma by the prognostic criteria. Therefore, salvage surgery remains essential in the treatment of advanced testicular cancer.     

Improved chemotherapy in disseminated testicular cancer.

Two combination chemotherapy regimens for disseminated testicular cancer are described. Our present regimen of platinum vinblastine and bleomycin has been highly successful, producing 16 complete (80 per cent) and 4 partial (20 per cent) remissions. Furthermore, 2 patients have been rendered free of disease by the surgical removal of residual disease, making the effective complete remission rate in these 20 patients 90 per cent. Of these patients 16 are alive and 14 are free of disease for more than 8 to more than 20 months. Despite the significant toxicity during the first 12 weeks of this therapeutic regimen it usually was manageable and maintenance therapy produced minimal toxicity. We believe that this regimen is a major advance in the management of patients with disseminated testicular cancer.     

Orchidectomy after chemotherapy for patients with metastatic testicular germ cell cancer

OBJECTIVE: To evaluate the contribution of routine orchidectomy in the management of patients who present with advanced, metastatic, testicular germ cell cancer and who are treated with initial chemotherapy. PATIENTS AND METHODS: Sixty consecutive patients presenting with metastatic testicular germ cell cancer and treated with initial chemotherapy followed by orchidectomy were identified. The results from a clinical and pathological review of these patients are presented. The pathological findings at orchidectomy were compared with the pathological findings from metastatic masses resected after chemotherapy, and are reviewed with the clinical outcome. RESULTS: Of the 60 orchidectomy specimens after chemotherapy, 24 (40%) contained significant histological abnormalities comprising residual invasive germ cell cancer, intratubular germ cell neoplasia and/or mature teratoma. The remaining 36 (60%) orchidectomy specimens contained fibrous scarring with or with no necrosis. Six (10%) orchidectomy specimens contained residual invasive germ cell cancer, three nonseminomatous germ cell cancer (NSGCT) and three seminoma. The patients with residual invasive NSGCT present within the testis had evidence of residual invasive NSGCT within extragonadal masses resected after chemotherapy; all three have relapsed and died from chemorefractory progressive disease. CONCLUSION: Orchidectomy after chemotherapy is recommended in all patients undergoing primary chemotherapy, as a significant proportion (40%) are left with histological abnormalities that predispose to subsequent relapse. Persistence of invasive NSGCT at the site of the primary tumour after chemotherapy is associated with persistence of invasive disease at other metastatic sites and is a poor prognostic finding.     

The salvage chemotherapy for refractory testicular cancer with novel anticancer agents

Despite the generally high cure rate in patients with metastatic testicular cancer, 20% to 30% of treated patients will become candidates for salvage chemotherapy. We reviewed the recent salvage chemotherapy trials of refractory diseases. CPT-11 is a new derivative of camptothecin and has activity in a variety of solid tumors. We evaluated the antitumor effect of combination chemotherapy using CDDP and CPT-11 against refractory testicular cancer. Fourteen patients who failed to achieve complete remission with salvage chemotherapy were treated with combination chemotherapy with CPT-11 and CDDP or 254-S (nedaplatin) as third line chemotherapy. Six patients remain alive and disease-free and 5 patients died of disease. The combination of CPT-11 and either CDDP or nedaplatin was significantly more effective than other salvage therapy regimens such as VIP. Paclitaxel, ifosfamide, etoposide regimens were also effective in patients with refractory testicular tumors. We concluded that these combination regimens demonstrated significant activity against refractory testicular tumor and further investigation is warranted.     

Nerve-sparing retroperitoneal lymph node dissection for advanced testicular cancer after chemotherapy

BACKGROUND: Nerve-sparing techniques are commonly used in retroperitoneal lymph node dissection (RPLND) in patients with early stage testicular germ cell tumors to preserve postoperative ejaculation. The indications for nerve-sparing procedures have been extended to patients who have residual retroperitoneal tumor postchemotherapy with an increase in the incidence of local recurrence. Here, we report on 26 Japanese men with advanced testicular cancer who underwent nerve-sparing RPLND after partially successful chemotherapy. METHODS: Between January 1995 and December 2000, 26 patients with metastatic or recurrent testicular cancer underwent nerve-sparing RPLND after chemotherapy. Eight patients had seminoma and 18 had non-seminoma. Three patients received high-dose chemotherapy with carboplatin (250 mg/m2 per day x 5 days), etoposide (300 mg/m2 per day x 5 days) and ifosfamide (1.5 g/m2 per day x 5 days) in combination with peripheral blood stem cell transplantation. RESULTS: In all cases, lumbar splanchnic nerves were preserved macroscopically during the operation, at least unilaterally. Twenty-two patients (84.6%) achieved antegrade ejaculation during a mean follow-up at 3.9 months (range: 1-7 months). Three patients have fathered children. Only one patient suffered a retroperitoneal recurrence during a median follow-up at 25.8 months (range: 6-76 months). CONCLUSION: Nerve-sparing procedures for RPLND are appropriate for patients with metastatic testicular cancer, even after chemotherapy. The procedure preserves ejaculatory function in the majority of the patients without increasing the risk of local recurrence. Nerve-sparing RPLND improves the quality of life in patients who require postchemotherapy RPLND to treat residual tumor.