Prognostic factors for patients with advanced seminoma treated with platinum-based chemotherapy

Prognostic factors for 3-year progression-free survival (PFS) were defined in 286 patients with advanced seminoma treated with cisplatin-based chemotherapy at 10 European oncology units (no prior treatment: 236; prior radiotherapy: 50). Previously irradiated patients displayed a 69% PFS as compared to 87% in those presenting with advanced seminoma at the time of diagnosis (P = 0.009). In the univariate analysis, the extent and site of disease before chemotherapy and the level of serum LDH (< 2.0 versus > or = 2.0 x upper limit of normal) correlated with PFS in previously non-irradiated patients, but not in patients with prior radiotherapy. The multivariate analysis was, therefore, restricted to previously non-irradiated patients. The presence of non-pulmonary visceral metastases and a serum LDH level of > or = 2 x normal (N) proved to be independent prognostic factors. Based on these variables, two prognostic models were constructed and validated in an external data set of 166 comparable patients. For clinical use, Model 2 is recommended. The good-prognosis group comprises non-irradiated patients with stage II seminoma and any LDH level at presentation, or stage III and IV patients (with lung metastases only) whose serum LDH level is < 2 x N. These patients display a 94% 3-year PFS. The poor prognosis group includes all other patients with a 56% PFS. With this prognostic model, individualisation of the therapeutic approach may be considered in patients with advanced seminoma and a high risk of chemotherapy-related toxicity.     

Do patients with advanced breast cancer benefit from chemotherapy?

This study aimed to assess the proportion of patients with advanced breast cancer who report benefit from first-line palliative chemotherapy using a simple global measure of wellbeing and to identify factors predicting benefit. A consecutive series of women with advanced breast cancer undergoing first-line palliative chemotherapy was evaluated. The main outcome measure was patient report of overall wellbeing assessed at post-treatment interview. Physical, psychological and functional status were assessed using the Rotterdam Symptom Checklist (RSCL) on three occasions (pretreatment, at the start of the third cycle and post treatment). It was planned that treatment would be discontinued after six cycles (i.e. 18-24 weeks). One hundred and sixty patients started treatment, of whom 155 were assessable for quality of life. After treatment, 41 (26%) patients reported they felt better, 29 (19%) felt the same and 34 (22%) felt worse than they did before treatment. The other 51 (33%) patients either died or stopped attending the hospital before the post-treatment interview and were assigned as treatment 'failures'. Patients who reported feeling better after treatment had improvements in psychological distress (P < 0.0001), pain (P = 0.01), lack of energy (P = 0.02) and tiredness (P = 0.02), as well as improvement in functional status (P = 0.07). Feeling better was also correlated with disease response (P = 0.03). Feeling worse after treatment or treatment 'failure' was predicted by the pretreatment presence of a dry mouth (P = 0.003) and high levels of psychological distress (P = 0.03). Pretreatment lack of energy (P = 0.01), dry mouth (P = 0.02), presence of liver metastases (P = 0.03) and breathlessness (P = 0.03) predicted treatment 'failures'. The results of this study suggest that first-line palliative chemotherapy for advanced breast cancer confers benefit on a substantial proportion of patients, with about one-quarter feeling better after treatment and nearly a half feeling better or the same some 4-6 months after the start of treatment. Factors identified in this study may assist clinicians in deciding which patients should not be offered treatment, because of high risk of feeling worse or treatment 'failure'. This work now needs to be validated on a further cohort of women receiving chemotherapy for advanced breast cancer.     

Prolonged survival in patients with advanced melanoma treated with neoadjuvant chemotherapy followed by resection

We conducted this cadaveric study to define a biomechanical rationale for rotator cuff function in several deficiency states. A dynamic shoulder testing apparatus was used to examine change in middle deltoid muscle force and humeral translation associated with simulated rotator cuff tendon paralyses and various sizes of rotator cuff tears. Supraspinatus paralysis resulted in a significant increase (101%) in the middle deltoid force required to initiate abduction. This increase diminished to only 12% for full glenohumeral abduction. The glenohumeral joint maintained ball-and-socket kinematics during glenohumeral abduction in the scapular plane with an intact rotator cuff. No significant alterations in humeral translation occurred with a simulated supraspinatus paralysis, nor with 1-, 3-, and 5-cm rotator cuff tears, provided the infraspinatus tendon was functional. Global tears resulted in an inability to elevate beyond 25 degrees of glenohumeral abduction despite a threefold increase in middle deltoid force. These results validated the importance of the supraspinatus tendon during the initiation of abduction. Glenohumeral joint motion was not affected when the "transverse force couple" (subscapularis, infraspinatus, and teres minor tendons) remained intact. Significant changes in glenohumeral joint motion occurred only if paralysis or anatomic deficiency violated this force couple. Finally, this model confirmed that rotator cuff disease treatment must address function in addition to anatomy.     

Weekly CAF chemotherapy for advanced breast cancer patients

BACKGROUND: Seromas and impaired shoulder function are well-known complications after modified radical mastectomy for breast cancer. Early postoperative physiotherapy is a common treatment to avoid shoulder dysfunction. The aim of this study was to evaluate if the frequency of postoperative seromas could be reduced, without increasing shoulder dysfunction, by delayed postoperative shoulder exercises. METHODS: In a prospective study 163 patients with breast cancer undergoing modified radical mastectomy were randomized to physiotherapy starting on postoperative day 1 or day 7. Patients were seen by the surgeons and the physiotherapists during hospital stay and in the outpatient department. Seromas and other complications were registered by the surgeons. The physiotherapists instructed the patients pre- and postoperatively and assessed shoulder function. RESULTS: There was a significantly higher incidence of postoperative seromas in the group of patients that started physiotherapy postoperative day 1 (38%) compared to the group that started physiotherapy postoperative day 7 (22%) (p < 0.05). There was no significant difference between the groups in the late outcome of shoulder function. CONCLUSION: The incidence of seromas after modified radical mastectomy for breast cancer is reduced by delaying shoulder exercises one week postoperatively. Earlier postoperative physiotherapy is not necessary to avoid impaired shoulder function.     

Carboplatin-based versus cisplatin-based chemotherapy in the treatment of surgically incurable advanced bladder carcinoma

BACKGROUND: The carboplatin-based chemotherapeutic regimen M-CAVI (methotrexate, carboplatin, and vinblastine) is active against bladder carcinoma and can be administered to patients who are ineligible to receive cisplatin or doxorubicin. The authors designed a randomized study to evaluate whether M-CAVI offers a therapeutic advantage over the cisplatin-based regimen M-VAC (methotrexate, vinblastine, doxorubicin, and cisplatin) in the treatment of patients with surgically incurable advanced bladder carcinoma. METHODS: Patients with surgically incurable advanced bladder carcinoma were enrolled on a randomized trial comparing M-CAVI, which consists of carboplatin (300 mg/m2 on Day 2, adjusted using Calvert's formula for an area under the curve of 5), methotrexate (30 mg/m2 on Days 1, 15, and 22), and vinblastine (3 mg/m2 on Days 2, 15, and 22) administered every 28 days, versus standard M-VAC. The eligibility criteria included histologically proven bladder carcinoma, surgically incurable disease, and no prior chemotherapy. Patients were treated until disease progression or unacceptable toxicity occurred. RESULTS: From January 1989 to January 1994, 47 assessable patients were included. Seventeen patients had lymph node disease and 30 had distant metastatic disease. Twenty-three patients were randomized to receive M-CAVI and 24 to receive M-VAC. Patient characteristics in the two groups were similar. Overall response rates were 39% (95% confidence interval [CI], 20-62%) for M-CAVI and 52% (95% CI, 30-73%) for M-VAC (P = 0.3), with 3 complete responses observed among patients treated with M-VAC and none among those in the M-CAVI group. M-VAC was associated with more gastrointestinal toxicity, stomatitis, alopecia, and Grade 4 neutropenia than M-CAVI. One toxicity-related death occurred in the M-VAC group. There was a statistically significant difference in median disease-related survival time favoring M-VAC (16 months; range, 6 to 22+) versus M-CAVI (9 months; range, 6 to 14+) (P = 0.03). CONCLUSIONS: M-CAVI is less toxic but less active than M-VAC in the treatment of patients with advanced bladder carcinoma. Carboplatin-based regimens in which carboplatin is administered at the dose range used in the current study should be reserved for patients who cannot tolerate cisplatin treatment. Further research is required to assess the impact of high dose carboplatin in the treatment of this disease.     

Ifosfamide and etoposide in previously treated patients with advanced breast cancer

AIMS AND BACKGROUND: Ifosfamide is an active alkylating agent in the treatment of breast cancer, as a first-line therapy and in advanced disease. Since the combination of etoposide with an alkylating agent produces a synergistic and tolerable activity in various malignancies, in the present study, ifosfamide and etoposide were administered to patients with advanced breast cancer to evaluate the response characteristics and the toxicity profile. STUDY DESIGN: The combination of ifosfamide, mesna and etoposide was prospectively administered to 41 previously treated patients with stage IV breast carcinoma. The treatment schedule consisted of ifosfamide, 1500 mg/m2, infused over 24 hrs with 1500 mg/m2 mesna on days 1 to 5 and 120 mg/m2 etoposide, infused over 1 hr on days 1 to 3, to be repeated every 4th week. RESULTS: After a median follow-up of 10 months, an objective response rate of 23% (overall 2.5% complete remission and 20.5% partial remission) and a median response duration of 5.3 months were obtained in 39 assessable patients. The non-responder group consisted of 28.3% stable disease and 48.7% progressive disease. The prior status of chemotherapy was the only significant prognostic factor with an impact on the response rate. The overall toxicity was generally mild, with grade 3 myelotoxicity encountered in 25.7% of patients. CONCLUSIONS: The tolerable side effect profile of the ifosfamide and etoposide combination might be advantageous as regards the quality of life. To improve the rate and/or the duration of response and to clarify the precise role of the ifosfamide-etoposide combination in previously treated advanced breast cancer, further trials are warranted.     

A case of locally advanced breast cancer successfully treated with intra-arterial infusion chemotherapy of high-dose epirubicin

A case of locally advanced breast cancer was treated with intra-arterial infusion chemotherapy using high-dose epirubicin. The 1st and 2nd cycle consisted of 210 mg (day 1, 4, 7) and 150 mg (day 1, 4, 7), respectively. After completion of 2 cycles of the regimen, remarkable loco-regional control and improved QOL were obtained. Leucopenia (nadir; 1,000/mm3) was the dose limiting factor, but well-tolerated with supportive therapy. The patient underwent salvage surgery and maintenance intra-venous chemotherapy (epirubicin; 30 mg/3 weeks). At this writing, the patient is enjoying favorable QOL. These findings suggested that this modality was effective for cases with exctensive loco-regional involvement.     

Survival and daily physical activity in patients treated for advanced midgut carcinoid tumors

BACKGROUND: Prospects for survival and quality of life ought to influence treatment strategies in patients with midgut carcinoids. METHODS: A total of 121 patients with midgut carcinoid received a combined medical and surgical treatment from 1980 to 1993. In all, 158 operations were undertaken for removal of mesentericointestinal lesions and occasional liver metastases or as repeat intervention for abdominal complications. Survival was analyzed together with estimates of daily physical activity during follow-up. RESULTS: Cause of death (63 patients) included carcinoid heart disease (41%) and cachexia (mesentericointestinal entrapment, 35%). Median survival was 11 years in patients with irresectable mesenteric metastases, 7 years with liver metastases, and 1 year with extraabdominal spread. Extensive liver metastases or substantial weight loss (9 kg or greater) reduced survival to a median of 4 to 5.5 years, and surgically treated intestinal ischemia reduced survival to a median of 8 years. Patients with carcinoid syndrome survived a median 7 years, those with 5-hydroxyindoleacetic acid values greater than 500 mumol/24 hr or a valvular heart disease survived a median of 5 years, those with heart failure a median of 2.5 years. Most patients retained an acceptable daily physical activity; impairment occurred in cases of malnutrition, high 5-hydroxyindoleacetic acid values, or heart valve fibrosis, and activity was markedly reduced in the presence of extraabdominal metastases or overt heart disease. CONCLUSIONS: Favorable survival statistics and the maintenance of daily physical activity support active medical and surgical management in patients with advanced midgut carcinoids.     

Two cases of advanced gastric cancer effectively treated with chemotherapy of 5-fluorouracil, cisplatin and cytarabine

We reported two cases of advanced gastric cancer effectively treated with chemotherapy of 5-fluorouracil (5-FU), cisplatin (CDDP) and cytarabine (Ara-C), 5-FU (300-350 mg/body) was given by continuous intravenous infusion. Ara-C (20-40 mg/body) by continuous infusion and CDDP (15-20 mg/body) were added intravenously for 3-6 days. For case 1, epirubicin (30 mg/body) was also given on the first day of each therapy course. Case 1 was a 62-year-old female who had gastric cancer with liver metastasis, ovarian metastasis and peritonitis carcinomatosa. After 3 courses of the chemotherapy, reduction of ovarian metastasis greater than 75% was observed. The value of CA125 decreased from 6,800 U/ml to 527 U/ml and ascites disappeared. Case 2 was a 54-year-old male who had type 3 advanced gastric cancer with multiple liver metastases. He received 6 courses of the therapy. Both primary and metastatic tumors showed over 50% reduction in tumor size. These suggested that this combination therapy was effective for inoperable advanced gastric cancers.     

Plasma insulin-like growth factor in primary breast cancer patients treated with adjuvant chemotherapy

Insulin-like growth factor 1 (IGF-1) plasma level was assayed in 60 breast cancer patients undergoing six courses of adjuvant chemotherapy. The only observed variation was a slight decrease (10%) in IGF-1 concentrations, assayed before treatment, between the first and the second courses of chemotherapy. During chemotherapy courses, there were no statistically significant variations in IGF-1. These results suggest that chemotherapy, unlike the specific hormonal treatments tamoxifen and somatostatin, certainly does not act via a decrease in plasma IGF-1.     

The fate of patients with locally advanced bladder cancer treated conservatively with neoadjuvant chemotherapy, extensive transurethral resection and radiotherapy: 10-year experience

PURPOSE: We assess the results of bladder preservation for infiltrating bladder cancer. The potential for neoadjuvant chemotherapy followed by extensive transurethral resection and radiotherapy was evaluated in 40 patients with T2-T4a G2-G3 bladder carcinoma. MATERIALS AND METHODS: From 1983 to 1995, 40 patients with bladder cancer underwent bladder sparing treatment, consisting of neoadjuvant chemotherapy, extensive transurethral resection and radiotherapy. Most patients had T3G3 cancer. A deep transurethral resection biopsy was performed before and after chemotherapy, and an extensive transurethral resection was repeated at the end of radiotherapy. Of the patients 30 received cisplatin and methotrexate and 10 also received vinblastine. Total dose of radiotherapy was 60 to 65 Gy. Recurrent superficial tumors were treated transurethrally. Radical cystectomy was considered for persistent or recurrent invasive disease. RESULTS: Complete response occurred in 19 patients (47.5%) after chemotherapy, and in 8 patients after transurethral resection and radiotherapy (67.5%). Within 10 years 8 responding patients (30%) had local recurrences and 3 underwent cystectomy. Of the patients 14 (35%) are alive, including 13 with no evidence of disease (mean survival 65 months), 5 died of unrelated disease and 21 (52.5%) died of distant metastases (mean survival 28 months). Of the 21 patients 14 had residual tumor after radiotherapy, 3 presented with distant metastases after vesical infiltrating recurrence and 4 had distant metastases in the absence of locoregional recurrence. In 22 patients (55%) the bladder was salvaged. Patients with complete response to chemotherapy had a low risk for recurrent infiltrating tumors and metastases. CONCLUSIONS: Complete tumor control was maintained at 5 years in more than 50% of the patients treated conservatively. Bladder salvage is feasible in select patients.     

Evaluation of efficacy and toxicity of tamoxifen in patients with advanced chemotherapy resistant ovarian cancer

47 patients with advanced ovarian cancer after routine treatment were treated with tamoxifen. Objective response rate (CR + PR) was 6.4%. 46.8% patients had stable disease with median time of stabilisation 6.9 m. Because of low toxicity and non satisfactory results of second line chemotherapy tamoxifen seems to be a useful treatment for this group of patients.     

Pattern of failure in patients with inflammatory breast cancer treated by alternating radiotherapy and chemotherapy

BACKGROUND: Patients with inflammatory breast cancer have a high risk of developing a local recurrence and/or distant metastases. Treatment with combined chemotherapy and locoregional radiotherapy contributes to a decrease in both risks. This study presents treatment results and evaluates the pattern of failure when an alternating chemoradiotherapy schedule is used. METHODS: One hundred twenty-five patients with nonmetastatic inflammatory breast cancer were treated with an alternating schedule of radiotherapy and chemotherapy. All women recruited were younger than 70 years of age and had a T4d, histologically proven infiltrating carcinoma with N0 to N2 axillary disease. The protocol consisted of three cycles of induction chemotherapy with doxorubicin, vincristine, cyclophosphamide, methotrexate, and 5-fluorouracil followed by three series of locoregional radiotherapy, delivering a total dose of 65-75 Gy to the breast tumor. Five additional cycles of chemotherapy with 5-fluorouracil/doxorubicin/cyclophosphamide were to be administered in between the first two and after the third radiotherapy course. A 1-week gap was respected between each course of chemotherapy and each series of radiotherapy. RESULTS: Toxicity was moderate and this strategy proved feasible although most of the patients only received six instead of the eight planned cycles of chemotherapy. Eighty-two percent of the patients achieved a complete response at the end of the treatment. The cumulative 5-year local failure and distant metastasis rates were 27% and 53%, respectively. Assuming competing events, local failures, contralateral recurrences, and distant metastases were the first site of failure in 18%, 5%, and 38% of patients, respectively. The 5-year overall and disease free survival rates were 50% and 38%, respectively. The main prognostic factor was tumor size. CONCLUSIONS: Alternating high doses of radiotherapy and chemotherapy is a feasible treatment schedule and permits breast conservation. Disease free survival is comparable to that of recently published series. As the main causes of failure are distant metastases, higher dose chemotherapy should be evaluated, in an attempt to further improve overall survival.     

A case of advanced vulvar cancer treated with combination therapy

Presented is a patient with advanced vulvar cancer involving the vagina, the perineum and the anus, with metastases to inguinal lymph nodes. The patient received irradiation and next, an artificial sigmoidal anus was made, with simultaneous vulvectomy performed with an electrosurgery. The patient's survival of 3 years and 3 months encourages to consider in such cases an attempt at applying aggressive surgical treatment combined with external radiotherapy.     

Survival of patients with carcinoma of the esophagus treated with combined-modality therapy

Since 1985, 229 cases of carcinoma of the esophagus have been considered for entry into a protocol with the use of preoperative chemotherapy and radiation therapy followed by surgical intervention as the primary element of treatment. One hundred sixty-five patients (93 with adenocarcinoma and 72 with squamous cell carcinoma) had esophagogastrectomy. The 5-year survival of the protocol patients who underwent resection was 25% for both groups--squamous cell carcinoma and adenocarcinoma. Of the protocol patients with squamous cell carcinoma who underwent resection, 40% had a sterilized specimen, whereas of those with adenocarcinoma, 20% had a sterilized specimen. If the patient had a sterilized specimen, the 5-year survival was approximately 60% for adenocarcinoma and 40% for squamous cell carcinoma. Those patients with adenocarcinoma and Barrett's esophagus had a 5-year survival of 55%. Of the patients who underwent only esophagectomy and esophagogastrectomy and had not been entered into the protocol, none lived beyond 3 years. The operative mortality rate for those who had esophagogastrectomy was 5%. Sixty-four patients completed the radiation therapy and chemotherapy but did not undergo surgical procedures because of progressive disease or refusal. Of those patients who completed chemotherapy and radiation therapy without surgical intervention, 5-year survival was 18% in patients with squamous cell carcinoma, whereas no patients with adenocarcinoma survived beyond 3 years. The finding of a sterilized specimen after esophagectomy is a favorable prognostic factor in patients with adenocarcinoma or squamous cell carcinoma. The finding that patients with Barrett's esophagus and adenocarcinoma have an improved chance for survival is perhaps related to an earlier diagnosis. It is clear that some patients with squamous cell carcinoma who did not undergo surgical procedures did have a sterilized specimen, because the survival in this group approached 20% at 5 years.     

Two cases of adenosquamous cell carcinoma of advanced cervical cancer treated by carboplatin-based chemotherapy with peripheral blood stem cell autotransplant

In two cases with adenosquamous cell carcinoma of advanced cervical cancer, carboplatin-based chemotherapy was given intraarterially from the internal iliac artery as neoadjuvant chemotherapy, and peripheral blood stem cells (PBSCs) were harvested. After the operation, conventional intravenous chemotherapy with PBSC autotransplant was performed. PBSCs were mobilized by neoadjuvant chemotherapy and G-CSF administration. By the apheresis procedures, 0.7-2.6 x 10(6)/kg CD34 positive cells were obtained. They had no severe side effects from intravenous chemotherapy with PBSCT, and they were free of disease 20 months. Neoadjuvant chemotherapy and G-CSF administration may be capable of mobilization of PBSCs, and chemotherapy with PBSCT may be useful in radioresistant advanced adenosquamous carcinoma of the cervical cancer.