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Biomedical subjects

A Berruti

Publications and source records attributed to A Berruti.

At least 55 records · Page 3Linked to original sources

Mitotane associated with etoposide, doxorubicin, and cisplatin in the treatment of advanced adrenocortical carcinoma. Italian Group for the Study of Adrenal Cancer.

BACKGROUND: The use of either mitotane or chemotherapy in the treatment of advanced adrenocortical carcinoma (ACC) has led to scanty and controversial results. The recent finding that mitotane is able to reverse in vitro multidrug resistance has provided a rational basis for combining this agent with cytotoxic drugs. The association of mitotane with etoposide, doxorubicin, and cisplatin (EDP) in the treatment of patients with advanced, inoperable ACC was tested in an Italian multicenter Phase II trial. METHODS: Twenty-eight patients (18 women and 10 men; median age, 47 years; range, 27-65 years) with measurable disease were enrolled in the study and evaluated for toxicity and response. There were 18 patients with clinical and/or biochemical evidence of steroid hypersecretion. An EDP schedule (etoposide 100 mg/m2 on Days 5-7, doxorubicin 20 mg/m2 on Days 1 and 8, and cisplatin 40 mg/m2 on Days 1 and 9) was administered intravenously every 4 weeks; concomitantly, patients were given up to 4 g/day of oral mitotane or the maximum tolerated dose, without any interruption between chemotherapy cycles. RESULTS: According to World Health Organization criteria, complete response was achieved in 2 patients and partial response in 13, for an overall response rate of 53.5% (95% CI, 35-72%). Stable disease was observed in 8 patients and progressive disease in 5. Responses occurred in patients with both functioning and nonfunctioning tumors, and more often in those bearing lymph node and lung metastases. Time to progression in responding patients was 24.4 months. Generally, the EDP regimen was well tolerated. Only 4 patients received reduced doses, whereas 3 discontinued early chemotherapy due to toxicity. The addition of mitotane increased neurologic and gastrointestinal side effects. Due to these additional toxicities, only 9 patients regularly took the drug at the planned dose (4 g/day); 11 received the maximum tolerated dose of 3 g/day, 6 received 2 g/day, and 1 received 1 g/day. Mitotane was also responsible for raised serum levels of cholesterol and triglycerides. A complete hormone response (normalization of altered biochemical parameters) was observed in 9 of 16 evaluable patients with functioning tumors. CONCLUSIONS: EDP plus mitotane combination chemotherapy appears to be active and manageable treatment for patients with advanced ACC.

Administration, Oral↗

Cisplatin, epirubicin, and lonidamine combination regimen as first-line chemotherapy for metastatic breast cancer: a pilot study.

We assessed the activity and tolerability of a cisplatin, epirubicin, and lonidamine combination regimen as first-line chemotherapy in 28 advanced breast cancer patients. The schedule of treatment was as follows: 60 mg/ m2 epirubicin followed by 40 mg/m2 cisplatin given on days 1 and 2 every 21 days, with 450 mg lonidamine being given per os (three tablets) on days of chemotherapy administration and in the period intervening between one cycle and the next. Patients received a median of 5 (range 1-6) cycles. Overall, 22 patients were evaluable for response and 28, for toxicity. Four patients refused to continue the treatment after the first course, one was lost to follow-up, and one died due to toxicity (septic shock). The incidence of grade 3/4 nausea and vomiting was found to be greater than that expected with epirubicin and lonidamine alone. The addition of cisplatin resulted in an increase in platelet and hemoglobin toxicities, whereas the WBC toxicity did not differ from that expected with epirubicin and lonidamine. The hematological toxicity was found to be cumulative, leading to treatment delay in about 50% of patients at the fifth and sixth courses. The activity of this cytotoxic regimen was noteworthy, with the overall response rate being 81.8% (31.8% complete responses and 50.0% partial responses) in evaluable patients. This response rate decreased to 64.2% when all registered patients were included according to an intent-to-treat analysis. In conclusion, the association of cisplatin, epirubicin, and lonidamine given on the schedule described herein, appears to be very active but substantially toxic. We are now testing this combination in a randomized comparison, with the cisplatin dose being reduced to 30 mg/m2 given on days 1 and 2.

Administration, Oral↗

Cytotoxic and antiproliferative activity of the CMF regimen administered in association with tamoxifen as primary chemotherapy in breast cancer patients.

Seventy six consecutive patients with T2-4, N0-1, M0 primary breast cancer (BC) received a median of 3 cycles of CMF (cyclophosphamide, methotrexate, 5-fluorouracil) regimen. Tamoxifen was concomitantly administered in patients with estrogen receptor positive (ER+) BC. Ki67 antigen was evaluated immunohistochemically in tumor specimens obtained before chemotherapy and at mastectomy. At post chemotherapy evaluation, tumor shrinkage greater than 50% was obtained in 60 patients (78.9%), 21 of them being complete responders (27.6%). As a whole, primary chemotherapy significantly decreased the number of Ki67 positive cells. More than 50% decrease in Ki67 expression was observed in 78.9% of patients attaining a clinical complete response (CR), in 44.7% of patients with partial remission (PR) and in 50.0% of non-responders, while an increase (>25%) in Ki67 expression was found in 5.3%, 18.4% and 18.7% of patients with CR, PR and non-response, respectively. Both CR and PR rates were superimposable in patients with ER+ and ER- primary BC, while the reduction in Ki67 expression was mainly found in ER+ cases. Patients with increased Ki67 expression from baseline, at the end of primary chemotherapy, had a shorter disease-free interval (70 months) with respect to patients with no change (88+ months) or decrease (87+ months), p<0. 05. To conclude, the activity of CMF + tamoxifen in primary BC does not seem superior to that expected administering CMF alone. The reduction in Ki67 expression, as a whole, correlated with clinical CR, but some individual discrepancies between tumor shrinkage and Ki67 pattern have been observed. The Ki67 reduction mainly confined to the ER+ primary BC suggests that tumor response in this subset may be linked to the reduction in proliferation activity, whereas other mechanisms such as apoptosis might be responsible for the tumor shrinkage in ER- tumors. Since the increase in proliferation activity after primary chemotherapy was associated with a greater recurrence rate and lower disease free interval, irrespective of tumor response, changes in proliferation activity after primary chemotherapy may represent a potentially available parameter that, in addition to the tumor response, can discriminate patients who would benefit from the cytotoxic treatment from patients who would not.

Adult↗

Pamidronate administration improves the secondary hyperparathyroidism due to "Bone Hunger Syndrome" in a patient with osteoblastic metastases from prostate cancer.

BACKGROUND: The so-called Bone Hunger Syndrome is a metabolic derangement that sometimes complicates the natural history of prostate cancer patients with osteoblastic bone metastases. An excessive bone formation leads to calcium entrapment in bone and the subsequent increase of parathyroid hormone (PTH) levels, in response to calcium demand. PTH elevation stimulates the osteoclasts in sites distant from those involving the tumor, leading to osteomalacia. METHODS: PTH and markers of bone turnover were monitored every 3 weeks, from the start of pamidronate treatment in a prostate cancer patient with progressive disease, to luteinizing hormone releasing hormone analog (LHRH-A) administration, developing hyperparathyroidism, hypophosphatemia, and albumin corrected serum calcium close to the lower limit of normality. Serum bone alkaline phosphatase (BALP), assessed by two different methods: electrophoretic and immunoradiometric, and urinary levels of markers of bone collagen breakdown were also remarkably elevated. RESULTS: As a consequence of pamidronate infusion (60 mg e.v. every 3 weeks for a total of four times), BALP and PTH decreased consistently, serum calcium and phosphorus returned within the normal range, while markers of collagen resorption showed a significant decrease at the 9th week, preceded by a transient rise. CONCLUSIONS: This case report indicates that bisphosphonates could inhibit both osteoclast activity. The anti-osteoblastic effect is mainly responsible for the improvement of the pretreatment calcium imbalance of our patient towards hypocalcemia and the consequent hyperparathyroidism.

Aged↗

Comparison of assay of total and bone-specific alkaline phosphatase in the assessment of osteoblast activity in patients with metastatic bone disease.

The evaluation of response of osseous metastases to systemic treatments is often low as a consequence of the different radiologic appearances that make objective assessment not only difficult but sometimes impossible. Radiographic evidence of recalcification, the UICC criterion of response, is often evident for 6 months and sometimes may be delayed even more. This accounts for lower response rates in bone with respect to other metastatic sites in clinical trials. A transient rise in bone formation indices may provide an early indication of bone healing and, along with measurement of symptomatic changes, could ameliorate the response evaluation. Among the biochemical markers of bone formation, total alkaline phosphatase (TALP) is widely employed, but it lacks specificity. Estimation of bone isoenzyme (E-BALP) by electrophoretic techniques is time consuming and semiquantitative. The immunoradiometric assay (I-BALP) seems to overcome these limitations. In this study, we compared the two methods of bone isoenzyme estimation with each other and with the levels of bone gla protein (BGP) and carboxyterminal propeptide of type I procollagen (PICP) in a group of 136 cancer patients with bone metastases stratified as having lytic or mixed and blastic lesions at X-ray, and in 62 cancer patients without apparent bone involvement. The same indices were also evaluated prospectively in a patient subset submitted to chemotherapy associated with pamidronate. The aims of the study were to evaluate whether I-BALP is superior to E-BALP and whether both methods of bone isoenzyme estimation are more advantageous than TALP, BGP, and PICP in the assessment of osteoblast activity either in baseline conditions or in response to treatment. In bone metastatic patients with lytic appearances, values above the cut-off limit were observed in 32.1%, 23.3%, 48.9%, 32.9%, and 14% for, TALP, E-BALP, I-BALP, PICP, and BGP, while the corresponding percentages in those with blastic/mixed appearances were 74.0%, 84.8%, 76.9%, 51.9%, and 43.8%, respectively. In the patients without bone involvement, values within the normal range were 90.2%, 98.2%, 89.6%, 71.7%, and 90.2%, respectively. Levels of TALP, E-BALP, and I-BALP were reciprocally correlated in the three groups examined. In bone metastatic patients, however, the degree of correlation of the enzymes with PICP and BGP was weak. Liver isoenzyme of alkaline phosphatase (LALP) was found to correlate with E-BALP, but not with I-BALP, in patients with mixed/blastic lesions. Thirty-eight patients were submitted to pamidronate therapy (60 mg every 3 weeks, administered 4 times) in association with cytotoxic treatment. Osteoblastic markers were determined before any administration. Serum TALP, E-BALP, and I-BALP showed a transient rise in 9 cases, a progressive reduction in 12, no change in 2, and a progressive increase in 6. Changes in E-BALP and I-BALP from baseline were greater than those of TALP. A divergent pattern between TALP and both I-BALP and E-BALP was found in 9 patients, whereas a divergent temporal profile between the two methods of bone isoenzyme estimation was recorded in only 3 patients. Eight out of 38 cases obtained a partial recalcification of lytic and mixed lesions. Seven of them showed the concomitant early increase in TALP, E-BALP, and I-BALP followed by a gradual decline (osteoblastic flare), whereas 1 patient demonstrated the flare of E-BALP and I-BALP but not of TALP. No relationship was found between response and temporal changes in in BGP and PICP serum levels. We conclude that I-BALP is a useful marker for detecting excess osteoblastic activity in patients who have at imaging "pure" lytic bone metastases. In the longitudinal evaluation of patients receiving multiple pamidronate infusions plus chemotherapy, TALP, E-BALP, and I-BALP, but not BGP and PICP, appeared to be useful to identify responders in bone. (ABSTRACT TRUNCATED)

Adult↗

Relationship between CA 15-3 serum levels and disease extent in predicting overall survival of breast cancer patients with newly diagnosed metastatic disease.

In order to study the relationship between circulating levels of CA 15-3 and the disease extent in predicting survival, we prospectively followed 312 breast cancer (BC) patients, from October 1988 to March 1995, from the time of first relapse. CA 15-3 values were assessed before treatment onset. Disease extent was defined as the percentage of liver or lung involvement and the number of bone segments positive at scintigraphy. The covariates were primary tumour characteristics (T, N and hormone receptor status) and patient characteristics at recurrence (menopause, performance status and age). Higher CA 15-3 serum levels were found in patients with visceral metastases or with pleural effusion. A logistic regression model selected disease extent in liver, lung and bone as independent variables for the determination of abnormal CA 15-3 values. Univariate survival analysis confirmed the positive prognostic influence of low CA 15-3 serum levels, absence of visceral metastases and the presence of only one metastatic site. Multivariate Cox's survival analysis selected disease extent in liver, lung, bone and soft tissue but not level of CA 15-3 as prognostic factors. In conclusion, CA 15-3 is not an independent variable in determining survival, its prognostic role being linked to the disease extent. This association suggests that CA 15-3 may be useful in assessing disease extent when this is not easily assessable.

Adult↗

Influence of neoadjuvant chemotherapy on serum tumor markers CA 15-3, MCA, CEA, TPS and TPA in breast cancer patients with operable disease.

Serum levels of CA 15-3, mucinous-like cancer antigen, carcinoembryonic antigen, tissue polypeptide antigen and tissue polypeptide-specific antigen (TPS) have been determined in 99 patients with T2-4 N0-1 M0 breast cancer (BC) before and after primary (neoadjuvant) chemotherapy and after surgery. As a whole, no difference in marker levels was apparent according to tumor and patient characteristics, with the only exception of TPS values, which showed an inverse relationship with the histologic grade. Serum marker levels did not substantially change with respect to baseline either after chemotherapy, despite the high response rate obtained, or after surgery. These data indicate a limited contribution of the primary tumor to the serum marker levels and are consistent for the scarce usefulness of marker evaluation in BC patients with an early stage of disease. Interestingly, pretreatment elevated CA 15-3 levels were correlated with a higher recurrence rate, further supporting the prognostic significance of this tumor marker.

Adult↗

Multicenter Phase II trial of intermediate dose cisplatin and vinorelbine in inoperable non-small cell lung cancer patients.

Vinorelbine (VNB) and cisplatin (CDDP) combination regimen was found active in the treatment of advanced non-small cell lung cancer (NSCLC) patients, but significant toxicity was observed. We evaluated the activity and toxicity of this combination administered at lower doses than previously reported. From March 1992 to March 1994, 99 patients (pts) were enrolled in a multicentric Phase II study and received intravenous CDDP at 80 mg/m2 on day 1, associated with intravenous VNB at 25 mg/m2 on days 1 and 8. Cycles were repeated every 3 weeks. The reduced doses led to a consistently lower myelotoxicity (8% Grade III-IV leukopenia) in comparison to two related Phase III studies, recently published. Conversely, the incidence of neurological toxicity was superimposable. Considering all eligible patients, the overall response rate was 28.3%, and this is similar to the results commonly observed employing the most active CDDP containing regimens. In conclusion, CDDP and VNB combination chemotherapy at the schedule performed in the present study led to a reduction of hematologic toxicity, while an appreciable activity was maintained.

Adult↗

Biochemical evaluation of bone turnover in cancer patients with bone metastases: relationship with radiograph appearances and disease extension.

Serum bone alkaline phosphatase (BALP), serum carboxy-terminal propeptide of type I procollagen (PICP) and serum bone gla protein (BGP) as markers of bone formation, serum carboxy-terminal telopeptide of type I collagen (ICTP) as a marker of collagen resorption and fasting molar ratio of urinary calcium to creatinine (CaCr) and serum parathyroid hormone (PTH) were determined in two groups of cancer patients: 48 with advanced or metastatic disease with negative bone scan and 174 with bone metastases categorised as having lytic, mixed or blastic lesions and with more or fewer than or equal to three sites involved. In patients without apparent bone involvement, bone formation markers were rarely elevated. Conversely, serum ICTP was frequently found to be supranormal, showing it to be a non-specific marker for early detection of bone metastases. As expected, values of bone formation markers progressively increased in patients with lytic, mixed and blastic lesions, but ICTP levels did not show any differences according to the types of bone appearances, confirming previous reports of elevated osteoclast activity also in patients with apparent blastic lesions. Serum PTH increased significantly in patients with lytic compared with patients with mixed and blastic appearances, paralleling the bone formation markers, but CaCr showed the opposite pattern. These data are compatible with calcium entrapment in the bone in patients with increased osteoblast activity. This so called 'bone hunger syndrome' is further confirmed by the finding that in the subgroup of blastic appearances CaCr diminished whereas both ICTP and PTH increased according to the extent of tumour load in the bone.

Adult↗

Lonidamine significantly increases the activity of epirubicin in patients with advanced breast cancer: results from a multicenter prospective randomized trial.

PURPOSE: Some evidence in vitro and in vivo shows that lonidamine (LND) can positively modulate the activity of doxorubicin and epirubicin (EPI). On this basis, a multicenter prospective randomized trial was performed in patients with advanced breast cancer (BC) to determine if the addition of LND to EPI could increase the response rate of EPI alone. PATIENTS AND METHODS: From May 1991 to May 1993, 207 patients were enrolled onto this study and randomized to receive intravenous (IV) EPI (60 mg/m2 on days 1 and 2) alone or with LND (600 mg orally daily). EPI administration was repeated every 21 days until tumor progression or for a maximum of eight cycles. LND was administered continuously until chemotherapy withdrawal. RESULTS: Response rate was significantly superior for the EPI plus LND scheme compared with the single-agent EPI either considering assessable patients (60.0% v 39.8%; P < .01) or including all registered patients according to an intention-to-treat analysis (55.3% v 37.5%; P < .02). The distribution of the response rate according to the site of disease did not show any significant difference between the treatment arms, except for the patient subgroup with liver metastases in which the combination EPI plus LND resulted in a significant improvement of responses than EPI alone. Toxicity was moderate, and except for myalgia, no adjunctive side effects were observed in the EPI plus LND arm. Overall survival and time to progression were similar in both groups. CONCLUSION: This study confirms in vivo that the administration of EPI is enhanced by the concomitant LND administration.

Adult↗

Combination chemotherapy with carboplatin and methotrexate in the treatment of advanced urothelial carcinoma. A phase II study.

The activity and toxicity of a carboplatin (300 mg/m2, day 1) and methotrexate (50 mg/m2, days 8 and 15) combination chemotherapy in the treatment of advanced urothelial cancer (UC) was evaluated in the present study. A total of 49 patients entered the study: 44 patients were evaluable for response, and 48 for toxicity. A complete response (CR) was found in 4/44 patients (9.1%) and a partial remission (PR) in 12/44 patients (27.2%) for an overall response rate of 16/44 (36.3%). Stable disease was found in 21/44 patients (47.7%), and progressive disease in 7/44 patients (15.9%). Survival was significantly longer in responding patients than nonresponders (median: 62 weeks vs 50 weeks, P < .05). Hematologic and renal toxicities were mild, thrombocytopenia and leukopenia being the most relevant side effects. The first consecutive 7 patients received methotrexate also on day 22; 5 of them underwent grade III-IV hematologic toxicity, so methotrexate on day 22 was omitted in the subsequent patients. No toxic deaths were reported. CBDCA and MTX combination chemotherapy is well tolerated and moderately active in the treatment of advanced urothelial cancer and may represent a valid alternative to cisplatin-containing regimens in patients with poor performance status and/or impaired renal function.

Aged↗

Cytotoxic chemotherapy for adrenocortical carcinoma.

The efficacy of mitotane in providing objective tumour responses in patients with adrenocortical carcinoma (ACC), has been recently questioned. Experience with non specific chemotherapy is limited. Tumour responses have been reported with cisplatin administered as a single agent or in combination. Other reports however failed to show benefit from cytotoxic chemotherapy. The very low number of patients included in each study, mostly of them previously treated with mitotane, may account for these controversial results. The finding that multidrug resistance mediated by MDR-1/P-glycoprotein can be reverted by mitotane provides a rational basis for exploring the use of mitotane in combination with chemotherapeutic agents. In a multicenter cooperative (SWOG) phase II study, a combination of mitotane+cisplatin appeared active in advanced ACC, with 30% response rate in 37 eligible patients. These results prompted us to evaluate the activity of a combination chemotherapy of Eto-poside, Adriamycin and Cisplatin (EAP) in association with mitotane (4 g daily per os). Up to now we treated 6 patients, obtaining 3 partial responses. Recently, new drugs as suramin and gossypol have been show to have some activity in patients with surgically unresectable ACC, suggesting the need for further investigation. In conclusion, cytotoxic drugs+mitotane and new adrenocorticolytic/cytotoxic agents, should be explored as first line treatments in patients with advanced ACC. However, due to the extreme rarity of the disease, coordinated multicenter investigations should be highly encouraged.

ATP Binding Cassette Transporter, Subfamily B, Mem↗

Prognostic value in predicting overall survival of two mucinous markers: CA 15-3 and CA 125 in breast cancer patients at first relapse of disease.

The role of circulating tumour markers in providing prognostic information has been scarcely studied. We evaluated the prognostic significance of two mucinous markers: CA 15-3 and CA 125 in 115 breast cancer patients at first recurrence of disease. At diagnosis of advanced disease bone involvement was found in 64 patients, lung in 57, skin lymph nodes in 21, liver in 20, and brain in 5. Patients were recruited and treated in the same institution with conventional chemo- or endocrine therapy. The follow-up ranged from 3 to 54+ months (median 35). Serum samples were drawn at first recurrence of disease before the start of any endocrine and/or chemotherapy. Patients with CA 15-3 < 30 U/ml survived significantly longer than those with CA 15-3 > 30 U/ml (median 50+ versus 26 months, P < 0.02). Similarly, overall survival of patients with CA 125 < 35 U/ml was significantly higher in comparison with patients with CA 125 > 35 U/ml (median 34.5 versus 18.5 months, P < 0.001). CA 125, but not CA 15-3, maintained its prognostic value in the subgroup of patients with visceral metastases. Both markers were found to be independent prognostic variables in multivariate analysis according to Cox's model. CA 15-3 and CA 125 appeared to be powerful prognostic indicators, in addition to visceral metastases, in patients with advanced breast cancer.

Adult↗

Chemotherapy with dacarbazine and 5-fluorouracil in advanced medullary thyroid cancer.

BACKGROUND: Experience with chemotherapeutic agents in the management of advanced medullary thyroid carcinoma (MTC) is limited and controversial. However, since MTC is a neuroendocrine neoplasm, we considered the possibility that cytotoxic drugs previously used in the treatment of these tumours could also have activity in MTC. PATIENTS AND METHODS: Five patients (4 females and 1 male, aged 22-71 years) with locally advanced or metastatic MTC received 5 day intravenous courses of dacarbazine (DTIC) (250 mg/sqm) and 12 hour infusion 5-fluorouracil (450 mg/sqm), given every 4 weeks. Six cycles were administered to 4 patients and four to 1 patient. RESULTS: Three partial responses lasting 9, 10+ and 8+ months were observed; one patient had stable disease and one progressive disease. Toxicity was acceptable with grade I thrombocytopenia and grade II leukopenia occurring in one patient, and grade II nausea and vomiting in four patients. CONCLUSIONS: In our experience, treatment of advanced thyroid carcinoma with DTIC and 5-FU appeared to have significant activity and was well tolerated.

Adult↗

Neoadjuvant chemotherapy with adriamycin, cisplatin, vincristine and cyclophosphamide (ADOC) in invasive thymomas: results in six patients.

BACKGROUND: Locally advanced malignant thymomas are usually radically resectable in about 60% of stage III but hardly ever in stage IVA. Neoadjuvant chemotherapy followed by surgery could improve both resection rate and curability. Cisplatin containing regimens have repeatedly been found to be highly active in advanced disease, with overall response rates ranging from 80%-90%. PATIENTS AND METHODS: 3 patients with stage III and 3 with stage IVA invasive thymomas, according to Masaoka staging, entered the study. Histology was: lymphoepithelial 4 cases, epithelial 2 cases. 4 cycles of the ADOC scheme--Adriamycin (40 mg/sqm), cisplatin (50 mg/sqm) on day 1, vincristine (0.6 mg/sqm) on day 2, and cyclophosphamide (700 mg/sqm) on day 3, every 21 days--were administered to 5 patients, while 1 patient received 5 cycles. RESULTS: 5/6 patients (83.3%) attained partial responses and underwent radical surgery followed by two further ADOC cycles. The disease-free intervals were 5+, 6+, 15+, 16+, 26+ months. One patient showing stable disease at the end of the fifth cycle was referred to radiotherapy. Toxicity was tolerable: grade III (WHO) nausea/vomiting and leukopenia grade III occurred in 2 patients each. CONCLUSIONS: These results suggest that the ADOC scheme is active as a neoadjuvant approach in invasive thymoma stages III and IVA, rendering possible radical resectability in 83% of patients.

Adult↗

Favorable response of metastatic adrenocortical carcinoma to etoposide, adriamycin and cisplatin (EAP) chemotherapy. Report of two cases.

The usefulness of non-specific chemotherapy for advanced adrenocortical carcinoma (ACC) is controversial. We report on 2 young female patients (25 and 19 yr) who presented with a clinical picture of Cushing's syndrome due to histologically confirmed ACC. The first patient underwent radical surgery, but after a disease-free interval of 6 months a local recurrence was apparent. She was reoperated and treated with 6 courses of cisplatin and etoposide chemotherapy. Mitotane (8 g daily) was begun, but 2 months later debulking surgery was again performed. A second-line chemotherapy with the etoposide, adriamycin, cisplatin (EAP) scheme attained a partial remission lasting 7 months, then metastatic spread to the brain led to death of the patient. The survival time was 30 months. The second patient underwent radical surgery and adjuvant mitotane (4 g daily), but multiple lung and mediastinal metastases were diagnosed after an interval of 29 months. Chemotherapy with the EAP regimen (6 courses) without interrupting mitotane attained a partial remission lasting 21+ months. We suggest that the EAP scheme is active in advanced ACC and that its association with mitotane is feasible.

Adrenal Cortex Neoplasms↗