Jane L. Torkelson

Hypomagnesemia, renal dysfunction, and Raynaud's phenomenon in patients treated with cisplatin, vinblastine, and bleomycin

Thirty men with metastatic germ cell cancer were treated with cisplatin (20 mg/m2 administered intravenously, days 1–5), vinblastine, and bleomycin at 3‐ to 4‐week intervals for four to six courses. There was a sequential fall in serum magnesium (P < 0.001) with each course of therapy: 26 of the 30 patients (87%) became hypomagnesemic, and the median magnesium nadir was 1.1 meq/1. No acute clinical effects of the hypomagnesemia were observed. The mean creatinine clearance declined from 115 ml/minute before therapy to 65 ml/minute, and the mean serum creatinine rose from 0.9 mg/dl to 1.6 mg/dl after six courses of therapy. With a minimum follow‐up of 36 months, 13 of the patients (43%) have clinical evidence of Raynauds phenomenon. Severity of prior hypomagnesemia predicted an increased risk of Raynauds phenomenon. Renal dysfunction, hypomagnesemia, and Raynauds phenomenon are common chronic toxicities of vinblastine, bleomycin, and cisplatin therapy.

Stage II nonseminomatous testicular cancer: a 10-year experience.

Between 1970 and 1980, 82 patients with pathologic stage II nonseminomatous germ cell testicular carcinoma were treated at the University of Minnesota. Of the 30 patients treated with a retroperitoneal lymph node dissection, 22 (77%) relapsed. Of the 18 patients treated with retroperitoneal lymph node dissection and adjuvant radiotherapy, 12 (63%) relapsed. Sixteen patients received adjuvant chemotherapy before 1976, and 14 (87.5%) relapsed. After 1976, 18 patients received adjuvant chemotherapy (11 with cisplatin) and 2 (11%) have relapsed. No patient treated with cisplatin-based adjuvant chemotherapy has relapsed. The toxicity has been modest. Cisplatin-based chemotherapy is an effective and a safe adjuvant therapy for stage II nonseminomatous germ cell testicular carcinoma.

Tumor classification and size in germ-cell testicular cancer. Influence on the occurrence of metastases

The influence of local tumor spread (T‐classification) and of tumor size on the occurrence of metastases was studied in 241 patients with testicular germ‐cell neoplasms. All patients underwent thorough clinical or pathologic staging, or both, and were treated at the University of Minnesota Hospitals. Spread of tumor through the tunica vaginalis (T2) was associated with abdominal lymph node or distant metastases in eight of nine patients. Local tumor extension to the spermatic cord (T4a) was associated with metastatic spread in 29 of 31 men. Tumor size did not appear to correlate with metastatic rate. These findings are an important aid in designing adjuvant therapy trials and in establishing a “no treatment” approach after orchiectomy.

Uracil mustard revisited.

A patient with diffuse large cell lymphoma who had a complete response lasting 35 years following a 3‐day course of uracil mustard stimulated a recall review of patients treated with this oral alkylating agent.

Optimal number of chemotherapy courses in advanced nonseminomatous testicular carcinoma.

BackgroundNonseminomatous germ cell tumors (NSGCT) (testicular carcinoma) are a curable disease. Stages I and II are nearly 100% curable. Stage III has had remarkable progress in attaining complete regression, but a substantial number fail to be cured. Using platinum-based regimens such as vinblastine, bleomycin, and cisplatin (VBP), or using etoposide instead of vinblastine (BEP), or without bleomycin (EP), four courses of chemotherapy have become a national standard. Based on our prior experience with mithramycin (plicamycin), which used six courses, six courses of VBP chemotherapy were utilized as our treatment goal. This report challenges the concept that “standard therapy” for stage III testicular carcinoma is four courses. MethodFrom 1976 to 1990, 74 patients with advanced NSGCT were treated with standard doses of platinum-based chemotherapies. Five or more courses were delivered to 41 patients and fewer than five courses to 33 patients. The intent of therapy was to attain as close to six courses as possible. Because of physician preference, patient adherence, or toxicity, some patients did not reach that goal. ResultsOf 33 patients receiving less than five courses, there were 28 (85%) complete responders, and 26 (78.8%) are alive. Of 41 patients receiving five or more courses, 38 (92.7%) had complete responses, and 34 (83%) are alive. One person in each group is living with nonresectable teratoma present. In the group receiving 5+ courses, two died from causes unrelated to testis cancer and had no testis cancer present. As a result of the initial treatment, there was no evidence of cancer in 24 (72.8%.) in the group receiving less than five courses and 35 (85.4%) had no cancer after five or more courses. In considering only patients with advanced level of stage III disease in contrast to minimal or moderate stage III disease, there were fewer complete regressions with less than five courses (64.3%) than with five or more courses (88.0%). ConclusionsFor minimal stage III disease, four courses of chemotherapy may be adequate. For advanced stage III disease, more chemotherapy provides fewer treatment failures. Once a complete response is achieved without restriction to an arbitrary number of courses, two additional courses may constitute a more curative regimen.

Extragonadal abdominal germ cell cancers

The charts of eleven patients with abdominal germ cell tumors were reviewed; one had a seminoma. They all had normal testes by physical examination. Therapy consisted of cisplatinbased chemotherapy and, in some cases, surgical debulking. A complete clinical response occurred in seven patients (63%). Two patients relapsed after achieving pathology complete responses and died of progressive disease despite second-line chemotherapy. All patients that failed to achieve a complete clinical response died of progressive disease. Five patients (45%) are long-term disease-free survivors, having no recurrence 4–10 years from the time of the diagnosis (median 6 years). The outcome for this group of patients did not differ significantly from that for patients with mediastinal germ cell tumors in this institution. They do not fare as well as patients with testicular cancer.

Health-related quality of life in children with congenital adrenal hyperplasia

BackgroundChildren with congenital adrenal hyperplasia (CAH) require life-long glucocorticoid replacement and have daily intermittent hyper/hypocortisolemia and hyperandrogenemia. Health-related quality of life (HRQL) is important for understanding the impact the disease and therapy have on physical, mental, emotional, and social functioning. Little is known about HRQL in CAH. We compared HRQL in children with CAH to healthy norms and examined how these scores related to physiologic variables.MethodsA cross-sectional study examined 45 patients (mean age 8.2(4.5) years). Thirty-two self-reported their quality of life (QoL) on the PedsQL™ Generic Core Scale and PedsQL™ Fatigue Scale, and 44 parents completed a parent report. Bone age Z-scores were calculated from the most recent bone age.ResultsChildren with CAH did not report lower QoL than healthy norms. However, their parents reported lower overall QoL and fatigue scores than parents of healthy norms. Children with CAH rated sleep poorer than their parents. QoL scores did not differ by sex or CAH subtype and were not associated with total daily hydrocortisone dose. Bone age Z-scores were negatively associated with child-reported emotional health and cognitive fatigue.ConclusionsParents of children with CAH reported a negative impact of disease on their children’s QoL, but their children did not. The negative associations between bone age Z-scores and emotional health and cognitive fatigue suggest an impact from chronic hypocortisolemia and hyperandrogenemia.

Familial Hearing Loss and Cisplatin Therapy

Familial high-tone hearing loss in males is a recessive trait often unrecognized. Cisplatin chemotherapy may be associated with hearing loss. A review was made of audiograms in 85 patients with testicular carcinoma prior to cisplatin chemotherapy to determine the extent of preexisting familial hearing loss. Clinical histories defined patients exposed to high noise levels and other common causes of hearing loss. Audiometric findings were classified according to normal hearing or mild, moderate, and severe hearing impairment. Pretreatment audiograms were normal in 51 patients and abnormal in 19 patients with histories of high-level noise exposure, and in 15 patients with high-frequency hearing loss there was no history of noise exposure, ear infection, or other potential causes of hearing loss. These last 15 patients were judged to have recessive familial hearing loss. Awareness of familial hearing loss is important in male patients in whom cisplatin chemotherapy is planned. Pretreatment hearing assessment, including audiograms, is recommended for such male patients.

Adequacy of chemotherapy prior to cytoreductive surgery in testicular carcinoma

Removal of residual masses after cisplatin-based chemotherapy (cytoreductive surgery) for inoperable or metastatic testicular carcinoma has demonstrated that many partial regressions are defects without malignant cells. Such negative results allow a clarification of complete regression. Failure to achieve complete regression requires intensive salvage chemotherapy or bone marrow transplant. Extended initial chemotherapy could reduce these failures. Cytoreductive surgery was performed on 44 patients with inoperable stage II or stage III testicular cancer with residual defects following chemotherapy. The patients were evaluated according to whether (a) adequate treatment was given based on attaining normal markers followed by two additional courses of therapy, (b) normal markers were achieved but two additional courses were not administered, or (c) normal markers were never attained. These were subdivided into those receiving five or more courses of chemotherapy or fewer than five courses. Patients receiving two additional courses of chemotherapy after markers became normal had a low death rate (15.4%) and highest median follow-up. Fewer patients died if they had five or more courses of chemotherapy (11.8%). Of all those who attained normal markers with at least five or more courses of therapy, 10% are dead. The presence of residual malignant cells in those receiving five or more courses of therapy was 18.2% in contrast to 50% in those receiving fewer courses. Adequate chemotherapy and attainment of normal markers followed by two more courses of therapy results in fewer patients with residual malignant cells, a greater potential of cure, and less need for intensive salvage regimens.