Neoadjuvant chemotherapy with ifosfamide, cisplatin, and vinorelbine in advanced squamous cell carcinoma of the cervix.

A phase II trial was performed to assess the efficacy and toxicity of a combination of ifosfamide (IFX), cisplatin (CDDP), and vinorelbine (VNB) as neoadjuvant chemotherapy (NAC) for untreated advanced cervical carcinoma (ACC). Between October 1995 and February 1998, 40 patients were entered in this study. Their median age was 43 years (range: 23-74 years). International Federation of Gynecology and Obstetrics stages were: IIB, 23; IIIB, 13; and IVA, 4. Therapy consisted of: IFX 2,000 mg/m2 1-hour (H) IV infusion days 1 to 3; 2-mercaptoethanesulfonic acid sodium salt (mesna) 400 mg/m2 IV bolus H 0 and 4, and 800 mg/m2 by mouth H 8, days 1 to 3; VNB 25 mg/m2 20-minute IV infusion days 1 and 8; and CDDP 75 mg/m2 IV day 3. Cycles were repeated every 28 days for a total of three courses. Both staging and response (R) assessment were performed by a multidisciplinary team. An objective response (OR) was observed in 24 of 40 patients (60%; 95% confidence interval, 45-75%). Four patients achieved complete response (CR) (10%); 20 partial response (50%); 12 patients stable disease (30%); and 4 progressive disease (10%). Eight of 24 patients (33%) with OR underwent radical surgery, and histologic CRs were recorded in 2 of them. The remaining patients received definitive radiotherapy after NAC. The dose-limiting toxicity was myelosuppression. Leukopenia occurred in 32 patients (80%) and was grade III or IV in 14 patients (36%). Peripheral neuropathy occurred in 9 patients (22%), whereas myalgias occurred in 10 (25%). Constipation was observed in 9 patients (23%); emesis occurred in 35 patients (88%). There were no therapy-related deaths. These results indicate that IFX/CDDP/VNB is an active combination for ACC with moderate toxicity. Implementation of this regimen in a multimodal therapy protocol deserves further study.

Vinorelbine and paclitaxel as first-line chemotherapy in metastatic breast cancer.

PURPOSE: To evaluate the efficacy and toxicity of a combination of vinorelbine (VNB) and paclitaxel (PTX) as first-line chemotherapy in metastatic breast carcinoma (MBC). PATIENTS AND METHODS: Between August 1995 and August 1997, 49 patients with untreated MBC received a regimen that consisted of VNB 30 mg/m2 in a 20-minute intravenous (IV) infusion on days 1 and 8 and PTX 135 mg/m2 in a 3-hour IV infusion (starting 1 hour after VNB) on day 1. Cycles were repeated every 28 days. The median age of the patients was 52 years, and 59% of patients were postmenopausal. Median performance status was 1. Dominant sites of disease were soft tissue in 6%, bone in 29%, and viscera in 65%. RESULTS: Objective responses were recorded in 27 of 45 assessable patients (60%; 95% confidence interval, 46% to 74%). Complete remissions occurred in three patients (7%), and partial remissions occurred in 24 patients (53%). No change was recorded in 12 patients (27%), and progressive disease occurred in six patients (13%). The median time to treatment failure was 7 months, and median survival duration was 17 months. The limiting toxicity was myelosuppression, mainly leukopenia in 49 patients (100%) (grade 1 to grade 2, four patients; grade 3, 30 patients; and grade 4, 15 patients). Neutropenia was observed in 100% of patients (grade 1 to grade 2, three patients; grade 3, 11 patients; grade 4, 35 patients). Two treatment-related deaths due to febrile neutropenia were observed in patients with massive liver involvement. Peripheral neurotoxicity developed in 33 patients (67%) (grade 1, 25 patients; grade 2, eight patients); there were no grade 3 or grade 4 episodes. CONCLUSION: The combination of VNB-PTX showed significant activity as first-line chemotherapy for patients with MBC. Myelosuppression was the dose-limiting side effect, whereas neurotoxicity was mild to moderate.

Biochemical modulation of 5-fluorouracil by methotrexate in patients with advanced gastric carcinoma.

A phase II trial was conducted to evaluate the efficacy and toxicity of a modulation of 5-fluorouracil (5-FU) by methotrexate (MTX) (with leucovorin (LV) rescue) as first-line chemotherapy in patients with locally advanced (inoperable) or metastatic gastric carcinoma. From July 1993 through August 1996, 36 patients with advanced gastric carcinoma received a regimen that consisted of: MTX 200 mg/m2 diluted in 250 ml normal saline by intravenous infusion over 20 minutes at hour 0; 5-FU 1,200 mg/m2 intravenous push injection at hour 20. Beginning 24 hours after MTX administration all patients received LV 15 mg/m2 intramuscularly every 6 hours for six doses. Cycles were repeated every 15 days. One patient was not assessable for response. Objective regression was observed in 15 of 37 patients (43%; 95% confidence interval, 26%-60%). One patient (3%) achieved complete response and 14 (40%) achieved partial response. No change was recorded in 14 patients (40%) and progressive disease was noted in six patients (17%). The median time to treatment failure was 7 months and the median survival was 12 months. Toxicity was within acceptable limits but one therapy-related death resulting from severe leukopenia occurred. The dose-limiting toxicity was mucositis. Five episodes of grade 3 or 4 stomatitis were observed and caused dosage modifications of MTX and 5-FU. Biochemical modulation of 5-FU by MTX appears as an attractive modality in patients with advanced gastric cancer. Further investigation both in experimental and clinical fields is needed to clearly define its role and to design the best modulatory strategy.

Carboplatin (CBDCA) plus ifosfamide (IFO) as first-line chemotherapy in advanced (FIGO III and IV) ovarian cancer.

A phase II study of advanced FIGO III and IV ovarian cancer treated with carboplatin and ifosfamide was performed to define the efficacy and tolerability of this regimen as first-line chemotherapy. From November 1990 to December 1994, 30 women with advanced ovarian cancer or residual disease after initial surgery were treated with carboplatin (300 mg/m(2) intravenously on day 1) and ifosfamide (1,500 mg/m(2) intravenously on days 1-3, with MESNA) every 3 weeks. The overall response rate was 67% (complete response 27%, partial response 40%) and the median duration of response was 14 months (range, 6-36). After a median follow-up of 31 months, the median survival was 24.9 months. Time to progression (p<0.05) and overall survival were longer in the patient group subjected to debulking. This regimen was easily manageable with good activity and acceptable toxicity, and most patients were treated on an outpatient basis.

Survey on the use of questionable methods of cancer treatment. GOCS. Grupo Oncólogico Cooperativo del Sur República Argentina.

BACKGROUND: Despite the improvement of cancer treatments, unproven and useless therapies are widely adopted among cancer patients and their families. Little information is available on the actual magnitude of such a phenomenon. METHODS: Two anonymous, similarly aimed surveys were independently carried out in Italy and Argentina on cancer patients and their families by two research groups. RESULTS: Respectively 563 and 400 questionnaires were distributed. The percentage of patients and/or families involved in unsound care (17%) was similar in both surveys. Of these treatments, 20%-38% were proposed by physicians, but relatives, friends, and mass-media had an equally important role. The costs of such care was difficult to estimate. CONCLUSIONS: Real and exhaustive efforts are needed by Health Care Organizations, which must execute a policy of information and education towards the public and professionals, as well as declare unethical the use of unproven therapies which claim cancer cure but simply create false hopes. All oncologists should be aware of the use of these treatments for cancer patients, even concomitantly with conventional care.

High-dose cisplatin as neoadjuvant organ-preserving chemotherapy for squamous cell carcinoma of the larynx.

PURPOSE: We conducted this study to evaluate the efficacy and toxicity of fractionated high-dose cisplatin as neoadjuvant organ-preserving chemotherapy, followed by definitive radiotherapy, for untreated and advanced squamous cell carcinoma of the larynx. MATERIALS AND METHODS: From August 1990 to April 1994, 32 patients bearing previously untreated advanced squamous cell carcinoma of the larynx (12 stage III and 20 stage IV) received three courses of high-dose cisplatin (100 mg/m2 on day 1 and day 8 every 28 days) before definitive external radiation therapy with 65 to 70 Gy (180-200 cGy daily for 6-8 weeks). Twenty-eight patients were men; median age was 57 years (range, 31-69); and median performance status (ECOG) was 1 (0-2). RESULTS: With an average follow-up time of 18 months (range, 6-47), 30 patients are evaluable for response and 32 for toxicity. Responses after three courses of chemotherapy were: complete response, 18 patients (60%), and partial response, 7 patients (23%), for an overall response rate of 83%. Only one patient showed progressive disease. Fifteen patients (50%; 12 complete and 3 partial responders) had pathologic complete remission. Eighty percent of patients had no evidence of disease after the therapeutic program. Median disease-free survival was 24 months, and median overall survival was 28 months (range, 6-47). Overall, in 46% of all evaluable patients, organ preservation with acceptable function was achieved. Disease-free survival and larynx preservation were strongly correlated with pathologic complete remission. The average dose intensity received at the end of the third course of therapy was 47 mg/m2/week. There were no drug-related deaths. The main acute toxicity was grade 2-3 nausea and vomiting in 75% of patients. Two patients developed renal impairment after the first course of cisplatin. Ototoxicity (grade 2-3) was seen in 43% of patients, and peripheral neuropathy (grade 2-3) was observed in 12% of patients. In contrast, myelotoxicity and mucositis were mild. CONCLUSION: In conclusion, this strategy with fractionated high-dose cisplatin given on an outpatient basis is an attractive approach that produces a high rate of complete response and larynx preservation with an advantageous toxicity profile.

High-dose cisplatin with dipyridamole in advanced non-small cell lung cancer. A Grupo Oncológico Cooperativo del Sur study.

From March 1991 to October 1992, 41 patients with advanced non-small cell lung cancer (NSCLC) (20 stage IIIB and 21 stage IV) received a regimen consisting of cisplatin (CP) 100 mg/m2 i.v. days 1 and 8, and dipyridamole (DPD) 100 mg p.o. 75 minutes before CP, and then at hours 6, 12, and 18 as first-line chemotherapy. Cycles were repeated every 28 days for a total of 3. Median age was 56 years (range: 40-70). All patients had a performance status 0 to 1 and a weight loss < or = 10%. Squamous-cell carcinoma was diagnosed in 19 patients; adenocarcinoma in 16, and large-cell carcinoma in 6. A total of 37 patients were fully evaluable for response, whereas 39 were assessable for toxicity. No complete responses were observed: 5 patients (14%) achieved partial response; 23 patients (62%) showed no change, and progressive disease was observed in 9 (24%). The median time to treatment failure was 4 months, whereas median survival was 8 months. The average dose intensity received at the end of the third course of therapy was 46 mg/m2/week. There were no drug-related deaths. Toxicity was mild to moderate, with a high incidence of ototoxicity (54%) and emesis (67%). In conclusion, these results failed to demonstrate any significant advantage from a high-dose CP regimen modulated by DPD in patients with advanced NSCLC.

Ifosfamide and mitoxantrone as first-line chemotherapy for metastatic breast cancer.

PURPOSE: A phase II trial was performed to evaluate the efficacy and toxicity of a combination of ifosfamide (IFX) and mitoxantrone (MXN) as first-line chemotherapy for metastatic breast carcinoma. PATIENTS AND METHODS: Between January 1990 and August 1991, 48 patients with metastatic breast cancer were entered onto the study. Therapy consisted of IFX 2 g/m2 given as a 1-hour intravenous (IV) infusion on days 1 to 3; mesna 400 mg/m2 as an IV bolus immediately before and 4 hours after IFX administration and 2,000 mg orally 8 hours after IFX administration on days 1 to 3; and MXN 12 mg/m2 as an i.v. bolus on day 3. Cycles were repeated every 21 days until progressive disease (PD) or severe toxicity developed. RESULTS: One patient was considered not assessable for response. Objective regression (OR) was observed in 28 of 47 patients (60%; 95% confidence interval, 46% to 74%). Six patients (13%) had a complete response (CR) and 22 (47%) had a partial response (PR). The median time to treatment failure for the whole group was 9 months (range, 1 to 28); median survival was 19 months (range, 2 to 28). There were no treatment-related deaths. The limiting toxicity was myelosuppression. Leukopenia occurred in 37 patients (77%) and was grade 3 or 4 in 19 patients (40%). Nausea and vomiting were observed in 38 patients (80%), mucositis in 16 patients (33%), and grade 2 hematuria in two patients (4%). Eight patients (16%) developed mild neurotoxicity. CONCLUSION: The combination of IFX plus MXN is an active regimen against metastatic breast cancer with moderate toxicity that deserves further evaluation.

Impact of delay to treatment upon survival in 1067 patients with breast-cancer.

The medical records of 1067 patients with breast cancer were reviewed to evaluate the influence of delay between first symptom and first treatment upon survival. Three delay intervals were considered: <3 months; 3-6 months and >6 months. At a follow-up of 120 months, survival analyses identified a statistically significant difference (p=0.029) favoring patients with <3 months delay in the whole cohort, and in the group of women aged 50 or older (p=0.001). No differences were found when survival according to delay was considered within each clinical stage. A Cox multivariate analysis revealed that performance status, stage, age and menopausal status were significant predictors of survival for the whole group of patients. However, delay was an independent prognostic factor in patients with age greater-than-or-equal-to 50. In summary, 38/1067 patients (3.1%) could have been adversely affected by a >3 months delay between first symptom and first treatment. Better survival rate for patients with a short delay would obey to a greater number of patients in favorable stages and a higher proportion of women aged 50 or older in this group.

Development and validation of prognostic models in metastatic breast cancer: a GOCS study.

The significance of several prognostic factors and the magnitude of their influence on response rate and survival were assessed by means of uni- and multivariate analyses in 362 patients with stage IV (UICC) breast carcinoma receiving combination chemotherapy as first systemic treatment over an 8-year period. Univariate analyses identified performance status and prior adjuvant radiotherapy as predictors of objective regression (OR), whereas the performance status, prior chemotherapy and radiotherapy (adjuvants), white blood cells count, SGOT and SGPT levels, and metastatic pattern were significantly correlated to survival. In multivariate analyses favorable characteristics associated to OR were prior adjuvant radiotherapy, no prior chemotherapy and postmenopausal status. Regarding survival, the performance status and visceral involvement were selected by the Cox model. The predictive accuracy of the logistic and the proportional hazards models was retrospectively tested in the training sample, and prospectively in a new population of 126 patients also receiving combined chemotherapy as first treatment for metastatic breast cancer. A certain overfitting to data in the training sample was observed with the regression model for response. However, the discriminative ability of the Cox model for survival was clearly confirmed.

Neoadjuvant chemotherapy for cervical carcinoma.

Between October 1986 and August 1988, 33 previously untreated patients with locally advanced cervical carcinoma were studied to evaluate the efficacy and toxicity of a neoadjuvant chemotherapy combination consisting of cisplatin 50 mg/m2 intravenously (IV) on day 1, vincristine 1.4 mg/m2 IV on day 1, and bleomycin 25 mg/m2 IV in a 6-hour infusion on days 1-3. Cycles were repeated every 10 days for a total of three cycles, after which definitive radiation therapy (external and intracavitary) was administered. The median age was 47 years, and distribution by stages (International Federation of Gynecology and Obstetrics) was as follows: IIB, 12 subjects; IIIB, 19; and IVA, two. A multidisciplinary team conducted both staging and assessment of response to induction chemotherapy before the beginning of radiotherapy. Thirty-one women were fully evaluable for response and toxicity. No complete response was observed; seven subjects (23%) experienced a partial response, 18 (58%) had no change, and six (19%) showed progressive disease. Toxicity was mild to moderate and included nausea and vomiting, alopecia, hyperthermia, peripheral neurotoxicity, and anemia. We conclude that this regimen at this dosage and time interval produced a low number of objective regressions with a significant progression rate and is of doubtful value as neoadjuvant chemotherapy.

Advanced colorectal carcinoma. A prospective randomized trial of sequential methotrexate, 5-fluorouracil, and leucovorin versus 5-fluorouracil alone.

One hundred and twenty-five previously untreated patients bearing metastatic or advanced recurrent (inoperable) colorectal carcinoma and measurable disease were prospectively randomized. Those in arm A received 5-fluorouracil (5-FU), 1,200 mg/m2 i.v. infusion over 2 h, while those in arm B received methotrexate (MTX), 200 mg/m2 i.v. (push injection), followed 20 h later by 5-FU, 1,200 mg/m2 i.v. infusion over 2 h, plus calcium leucovorin (LV), 25 mg i.m. every 6 h for eight doses beginning 24 h after MTX administration. Cycles were repeated every 15 days. All patients receiving treatment were evaluable for toxicity and survival, and 118 patients were evaluable for response. The objective regression rate (complete plus partial response) was 12% (7 of 58) in arm A and 28% (17 of 60) in arm B (p = 0.049). No change was observed in 24% (14 of 58) in arm A and in 35% (21 of 60) in arm B (p = 0.28), while progressive disease was registered in 64% (37 of 58) and 37% (22 of 60) in arms A and B, respectively (p = 0.006). Median duration of response was 3 months in arm A and 5 months in arm B (p = 0.39). The median survival was 8.3 months in arm A and 11.2 months in arm B (p = 0.25). No statistically significant differences were found when objective regression and survival were related to site of primary tumor, performance status, and number of involved organs. There were two drug-related deaths in arm B due to severe myelosuppression followed by mucositis and sepsis. Of nonhematologic toxicities, diarrhea was more frequently observed in arm B, as were mucositis and infectious complications. Our results indicate that the sequential schedule MTX-5-FU-LV with 20-h intervals between MTX and 5-FU is superior in terms of objective regression to 5-FU alone given at the dose and schedule used in the present study. However, MTX-5-FU-LV did not have a significant impact on survival.

Seminoma puro de testículo: experiencia de tratamiento de 44 pacientes / Pure testicular seminoma: experience in treatment of 44 patients

Se revisaron las historias clínicas de 44 pacientes con diagnóstico de seminoma puro de testículo tratados entre 1981 y 1989. Veintiún pacientes (48%) fueron clasificados como estadio Iñ 16 pacientes (36%) como estadio IIAñ 4 pacientes (9%) estadio IIB y 3 pacientes (7%) estadio III. Tenían antecedentes de criptorquidia 7 pacientes (16%); de traumatismo testicular 9 pacientes (20%); orquiepididimitis 1 paciente (2%) y de malformación del aparato urogenital 1 pacientes (2%). El seminoma era típico en 43 pacientes (98%) y de variedad anaplásica en el paciente restante (2%). No hobu casos de seminoma espermatocítico. En 6 pacientes (14%) se halló un invel elevado de subunidad beta de gonadotropina coriónica humana persistente luego de la orquiectomía. Se identificaron en 2 de ellos células gigantes del sinciciotrofoblasto por medio de cortes seriados del espécimen quirúrgico. En todos los casos los niveles de este marcador sérico retornaron a valores normales luego del tratamiento primario radiante y/o quimioterápico. La sobrevida global para la totalidad de los pacientes es 96% a 8 años. Esto corresponde a un 100% para estadios I, IIA y IIB y 33% (1/3) para estadio III. No hubo fallas al tratamiento dentro de los campos de irradiación. Solamente 2 pacientes (5%) presentaron enfermedad recurrente en territorios extralinfáticos. Ambos fueron tratados exitosamente. La terapia fue en general bien tolerada y la toxicidad fue leve a moderada

Seminoma puro de testículo: experiencia de tratamiento de 44 pacientes / Pure testicular seminoma: experience in treatment of 44 patients

Se revisaron las historias clínicas de 44 pacientes con diagnóstico de seminoma puro de testículo tratados entre 1981 y 1989. Veintiún pacientes (48%) fueron clasificados como estadio Iñ 16 pacientes (36%) como estadio IIAñ 4 pacientes (9%) estadio IIB y 3 pacientes (7%) estadio III. Tenían antecedentes de criptorquidia 7 pacientes (16%); de traumatismo testicular 9 pacientes (20%); orquiepididimitis 1 paciente (2%) y de malformación del aparato urogenital 1 pacientes (2%). El seminoma era típico en 43 pacientes (98%) y de variedad anaplásica en el paciente restante (2%). No hobu casos de seminoma espermatocítico. En 6 pacientes (14%) se halló un invel elevado de subunidad beta de gonadotropina coriónica humana persistente luego de la orquiectomía. Se identificaron en 2 de ellos células gigantes del sinciciotrofoblasto por medio de cortes seriados del espécimen quirúrgico. En todos los casos los niveles de este marcador sérico retornaron a valores normales luego del tratamiento primario radiante y/o quimioterápico. La sobrevida global para la totalidad de los pacientes es 96% a 8 años. Esto corresponde a un 100% para estadios I, IIA y IIB y 33% (1/3) para estadio III. No hubo fallas al tratamiento dentro de los campos de irradiación. Solamente 2 pacientes (5%) presentaron enfermedad recurrente en territorios extralinfáticos. Ambos fueron tratados exitosamente. La terapia fue en general bien tolerada y la toxicidad fue leve a moderada (AU)

Bone-only versus visceral-only metastatic pattern in breast cancer: analysis of 150 patients. A GOCS study. Grupo Oncológico Cooperativo del Sur.

The medical records of 510 patients with metastatic breast cancer were retrospectively reviewed. Seventy-seven patients with metastases confined to skeleton and 73 patients bearing visceral-only disease were identified. All patients had a disease-free interval greater than or equal to 6 months and received systemic therapy with any of the following modalities: chemotherapy, hormonotherapy, or chemohormonotherapy. The clinical features, response to treatment, and survival were analyzed and compared for both groups. Median survival of patients with osseous metastases was 28 months, while it was 13 months for those patients with a visceral pattern (p less than 0.001). Response rates to first and second line systemic therapy for both metastatic patterns showed no significant differences, suggesting a similar degree of sensitivity or resistance in both groups. Objective regression to first therapy was 45% in the group with bony disease and 41% among patients with visceral involvement; median duration of response was 16 months and 13 months, respectively. In both groups progressive disease conserved the original metastatic pattern in most patients. We conclude that although a superiority in survival was evident for the osseous metastatic pattern, for these patients efforts should be made to select the least aggressive therapy in order to avoid excessive toxicity. Further studies are needed to confirm our findings.

Phase II trial of cytarabine, cisplatin and vindesine for advanced non-small cell lung cancer.

Thirty-two patients with advanced non-small cell lung cancer (NSCLC) were entered in this study to evaluate the efficacy and toxicity of a chemotherapy schedule including cisplatin (C) 40 mg/m2 intravenously (i.v.) on days 1-3; vindesine (V) 3 mg/m2 i.v. on day 1, and cytarabine (ara-C) 15 mg/m2 subcutaneously every 12 hours on days 1-3 (total dose: 90 mg/m2). Cisplatin was administered simultaneously with one dose of ara-C. Cycles were repeated every 28 days. Five patients out of 28 (18%) fully evaluable for response presented partial remissions. No complete response was observed. Median survival was 8 months and median duration of response was 4 months. Hematologic toxicity was severe in 3 patients. There were no toxicity-related deaths. Other adverse reactions included nausea and vomiting, alopecia and peripheral neuropathy. We conclude that this chemotherapy combination is marginally effective against NSCLC showing in this group of patients a low number of responses of short duration without a significant impact on survival.

[Pure testicular seminoma. Experience in treatment of 44 patients]. / Seminoma puro de testiculo. Experiencia del tratamiento de 44 pacientes.

The records of 44 patients with pure testicular seminoma treated from 1981 to 1989 were reviewed. Twenty-one patients (48%) had stage I disease; 16 patients (36%) stage IIA; 4 patients (9%) stage IIB and 3 patients (7%) stage III. A previous history of cryptorchism was present in 7 patients (16%); testicular trauma in 9 patients (20%); orchiepididymits in 1 patient (2%) and genitourinary malformation in 1 patient (2%). Typical seminoma was observed in 43 patients (98%) and anaplastic seminoma in the remaining one (2%). There were no patients with spermatocytic seminoma. An elevated level of beta-human chorionic gonadotropin persisting after orchiectomy was found in 6 patients (14%). Syncytiotrophoblastic giant cells were identified after serial sections of the surgically resected tissue in two patients. Levels of this serum marker returned to normal values after primary treatment in all patients. Overall survival for all patients is 96% at 8 years. This corresponds to 100% for stages I, IIA and IIB and to 33% (1/3) for state III. Two patients (5%) presented recurrent disease in extralymphatic territories. Both of them were successfully rescued with proper therapy. Treatment was generally well tolerated and toxicity was mild to moderate.

Seminoma puro de testiculo. Experiencia del tratamiento de 44 pacientes. / [Pure testicular seminoma. Experience in treatment of 44 patients]

The records of 44 patients with pure testicular seminoma treated from 1981 to 1989 were reviewed. Twenty-one patients (48

) had stage I disease; 16 patients (36

) stage IIA; 4 patients (9

) stage IIB and 3 patients (7

) stage III. A previous history of cryptorchism was present in 7 patients (16

); testicular trauma in 9 patients (20

); orchiepididymits in 1 patient (2

) and genitourinary malformation in 1 patient (2

). Typical seminoma was observed in 43 patients (98

) and anaplastic seminoma in the remaining one (2

). There were no patients with spermatocytic seminoma. An elevated level of beta-human chorionic gonadotropin persisting after orchiectomy was found in 6 patients (14

). Syncytiotrophoblastic giant cells were identified after serial sections of the surgically resected tissue in two patients. Levels of this serum marker returned to normal values after primary treatment in all patients. Overall survival for all patients is 96

at 8 years. This corresponds to 100

for stages I, IIA and IIB and to 33

(1/3) for state III. Two patients (5

) presented recurrent disease in extralymphatic territories. Both of them were successfully rescued with proper therapy. Treatment was generally well tolerated and toxicity was mild to moderate.

Relation between delay and survival in 596 patients with breast cancer.

To evaluate the influence of delay between first symptom and first treatment upon survival the medical records of 596 patients with breast cancer were reviewed. The following intervals were considered: less than 3 months; 3-6 months and greater than 6 months. Patients in the less than 3 months delay group had a better distribution by clinical stages and a 10-year survival rate higher than those in the longer delay groups (p = 0.034). However, within each stage no statistically significant difference in survival according to delay was observed. A Cox multivariate analysis revealed that performance status and stage of disease were independent predictors of survival, but not delay. Assuming the best prognosis for patients with clinical stages I and II and less than 3 months delay, the group with longer delay times had 15 deaths over what would have been predicted. This adverse effect was observed almost exclusively among patients over age 50 (14/15).

Stage IV breast cancer: clinical course and survival of patients with osseous versus extraosseous metastases at initial diagnosis. The GOCS (Grupo Oncológico Cooperativo del Sur) experience.

The medical records of 414 patients with metastatic breast carcinoma treated between 1978 and 1986 were reviewed and 44 women were identified as having stage IV disease when the primary breast lesion was detected. Of these 44 women, 25 had metastatic disease limited to the skeleton while 19 had extraosseous lesions only. The clinical features, response to therapy, and survival were analyzed and compared for both groups. The median survival of those patients with bone-only metastases was 52 months as compared with 13 months for those with extraskeletal lesions (p = 0.0025). The response rate to first-line systemic therapy was similar for both groups (47% for bone metastases and 44% for extraosseous metastases). The median duration of response was 14 months (range, 3-55 months) for patients with bone disease and 8 months (range, 4-43 months) for those with extraskeletal lesions. We conclude that patients with metastatic breast cancer confined to the skeleton at initial diagnosis tend to follow an indolent, chronic course with prolonged survival. Therefore the increase in response rate with aggressive chemotherapy should be balanced against its higher morbidity. Further studies are needed to confirm whether the better prognosis of these patients is determined by the anatomical confinement of the disease to the skeleton or merely reflects the influence of other prognostic factors.