Adrenocorticotropic hormone in the prevention of cisplatin-induced nausea and vomiting.

A double-blind trial to evaluate the antiemetic effects of adrenocorticotropic hormone (ACTH) in patients treated with cisplatin was performed. Thirty-seven adults with advanced cancer who were treated with cisplatin were randomly assigned to receive either synthetic long-acting ACTH (1 mg IM given 24 hours, 12 hours, and immediately preceding the administration of cisplatin) or a placebo given under the same conditions. All of the patients received chlorpromazine (50 mg IM) 30 minutes before cisplatin infusion. Patients receiving ACTH and chlorpromazine had significantly fewer episodes of vomiting (p less than 0.01) and shorter periods of nausea (p less than 0.02) than patients receiving placebo and chlorpromazine. Patients receiving ACTH and chlorpromazine were significantly more comfortable than patients receiving placebo and chlorpromazine. No important side effects were observed. ACTH may be an effective agent in preventing nausea and vomiting induced by cisplatin.

High-dose intensity oxaliplatin added to the simplified bimonthly leucovorin and 5-fluorouracil regimen as second-line therapy for metastatic colorectal cancer (FOLFOX 7).

This phase II study examined a regimen (FOLFOX7) of leucovorin (LV), high-dose intensity oxaliplatin, and 5-fluorouracil (5-FU), as second-line therapy for metastatic colorectal cancer. 48 patients were enrolled - 36 refractory and 12 resistant to prior therapy with LV-5-FU. Oxaliplatin (130 mg/m2) was infused with LV (400 mg/m2) over 2 h on day 1, followed by bolus 400 mg/m2 and a 46-h infusion (2400 g/m2) of 5-FU, every 2 weeks. Patients who responded or were stable received eight cycles. Patients were evaluated every 2 months. 20 patients (42%) had partial responses (95% confidence interval (CI): 28-56%), 19 (40%) had stable disease and 9 (19%) progressed. Median progression-free survival (PFS) was 6 months and median survival 16.1 months. Toxic effects of National Cancer Institute-Common Toxicity Criteria (NCI-CTC) grade 3/4 were: peripheral neuropathy 15%, nausea 8%, diarrhoea 11%, neutropenia 9%, thrombocytopenia 11%. Overall, 38% of patients experienced grade 3/4 toxicities, and 64% received 90% or more of the scheduled oxaliplatin dose intensity during the first four cycles. FOLFOX7 was highly active, with good tolerability, in pretreated patients resistant to LV-5-FU [corrected].

Oxaliplatin added to the simplified bimonthly leucovorin and 5-fluorouracil regimen as second-line therapy for metastatic colorectal cancer (FOLFOX6). GERCOR.

For patients resistant to leucovorin (LV) and 5-fluorouracil (5-FU), the addition of oxaliplatin (85 or 100 mg/m2) to bimonthly LV-5-FU has given a response rate of 20-46%. The highest response rate has been observed with oxaliplatin 100 mg/m2 (FOLFOX2). The present phase II study (FOLFOX6) infused oxaliplatin (100 mg/m2) with LV (400 mg/m2) as a 2-h infusion on day 1, followed by bolus 400 mg/m2 and a 46-h infusion (2.4-3 g/m2) of 5-FU, every 2 weeks. Among the 60 patients treated, 16 (27%) had partial responses (95% confidence interval: 15-38), 27 (45%) had stable disease, 15 (25%) experienced disease progression and 2 (3%) had non-measurable disease. From the start of FOLFOX6, median progression-free survival was 5.3 months and median survival 10.8 months. From the 448 cycles analysed, NCI-CTC grade 3-4 toxicities per patient were: peripheral neuropathy 16%, nausea 7%, diarrhoea 7%, mucositis 5%, neutropenia 24%, thrombocytopenia 2%. Overall 26 (46%) patients experienced grade 3-4 toxicities. Because of toxicity, only 36% of the patients received > or = 90% of the scheduled oxaliplatin dose intensity. FOLFOX6 was active in pretreated patients resistant to LV-5-FU and is being investigated as first-line therapy. We are now investigating FOLFOX7, a regimen with a higher oxaliplatin dose intensity and a lower 5-FU dose.

CPT-11 (irinotecan) addition to bimonthly, high-dose leucovorin and bolus and continuous-infusion 5-fluorouracil (FOLFIRI) for pretreated metastatic colorectal cancer. GERCOR.

CPT-11 (irinotecan) has shown activity in patients with advanced colorectal cancer resistant to leucovorin (LV) and 5-fluorouracil (5-FU). In this study, the simplified bimonthly LV-5-FU regimen was combined with CPT-11 (FOLFIRI) as third-line therapy for patients with advanced colorectal cancer. Continuous infusion of 5-FU was administered with disposable pumps as outpatient therapy. FOLFIRI consisted of CPT-11 180 mg/m2 as a 90-min infusion day 1; LV 400 mg/m2 as a 2-h infusion during CPT-11, immediately followed by 5-FU bolus 400 mg/m2 and 46-h continuous infusion of 2.4-3 g/m2 every 2 weeks. Among the 33 patients treated, 2 had partial responses for an overall response rate of 6%; 20 patients were stabilised (61%) and 11 had disease progression (33%). From the start of FOLFIRI, median progression-free survival was 18 weeks and median survival was 43 weeks. For the 242 cycles analysed, NCI-CTC toxicities grade 3-4 per patient were nausea 15%, diarrhoea 12% and neutropenia 15%. Overall, 10 patients (30%) experienced grade 3-4 toxicity. 7 patients (21%) had grade 2 alopecia. FOLFIRI generated activity and acceptable toxicity, in heavily pretreated patients, with limited diarrhoea, mostly asymptomatic neutropenia and manageable nausea and relatively uncommon alopecia. This regimen is suitable for studies in chemotherapy-naïve patients.

Combined radiotherapy and chemotherapy (cisplatin and 5-fluorouracil) as palliative treatment for localized unresectable or adjuvant treatment for resected pancreatic adenocarcinoma: results of a feasibility study.

PURPOSE: To evaluate a cisplatin-containing chemoradiotherapy (CRT) regimen followed by chemotherapy for unresectable (locally advanced group, n = 32) and resected (adjuvant group, n = 10) pancreatic adenocarcinoma. The quality of palliation and percentage of secondary resections were also studied for unresectable disease. METHODS AND MATERIALS: The protocol comprised CRT (45 Gy over 5 weeks), combined with 5-fluorouracil and cisplatin during the first and fifth weeks, followed, 3 weeks later, by 4 cycles of the same chemotherapy plus leucovorin. RESULTS: All patients completed CRT but only 50% of each group finished the entire protocol. Gastrointestinal toxicity and weight loss were the major side effects during CRT. Enhanced hematological toxicity limited the post-CRT chemotherapy. For the locally advanced group, median survival was 9 months; 1- and 2-year survival rates were 31 and 12. 5%, respectively. The overall response rate was 16% and 50% had stable disease. A lasting palliative effect defined as improved performance status and decreased analgesic consumption, was recorded for 43% of the patients. Only three secondary resections have been performed. For the adjuvant group, median survival was 17 months. CONCLUSIONS: Although toxic in advanced disease, this regimen significantly lowered pain and analgesic consumption, but had poor impact on secondary resectability. In an adjuvant setting, although equally toxic, this series was too small to allow conclusions to be drawn.

Local recurrences and distant metastases after breast-conserving surgery and radiation therapy for early breast cancer.

PURPOSE: To identify predicting factors for local failure and increased risk of distant metastases by statistical analysis of the data after breast-conserving treatment for early breast cancer. METHODS AND MATERIALS: Between January 1976 and December 1993, 528 patients with nonmetastatic T1 (tumors < or = 1 cm [n = 197], >1 cm [n = 220]) or T2 (tumors < or = 3 cm [n = 111]) carcinoma of the breast underwent wide excision (n = 435) or quadrantectomy (n = 93) with axillary dissection (negative nodal status [n-]: 396; 1-3 involved nodes: 100; >3 involved nodes: 32). Radiotherapy consisted of 45 Gy to the entire breast via tangential fields. Patients with positive axillary lymph nodes received 45 Gy to the axillary and supraclavicular area. Patients with positive axillary nodes and/or inner or central tumor locations received 50 Gy to the internal mammary lymph node area. A boost dose was delivered to the primary site by iridium 192 Implant in 298 patients (mean total dose: 15.2+/-0.07 Gy, range: 15-25 Gy) or by electrons in 225 patients (mean total dose: 14.8+/-0.09 Gy, range: 5-20 Gy). The mean age was 52.5+/-0.5 years (range: 26-86 years) and 267 patient were postmenopausal. Histologic types were as follows: 463 infiltrating ductal carcinomas, 39 infiltrating lobular carcinomas, and 26 other histotypes. Grade distribution according to the Scarff, Bloom, and Richardson (SBR) classification was as follows: 149 grade 1, 271 grade 2, 73 grade 3, and 35 nonclassified. The mean tumor size was 1.6+/-0.3 cm (range: 0.3-3 cm). The intraductal component of the primary tumor was extensive (EIC = IC > or = 25%) in 39 patients. Tumors were microscopically bifocal in 33 cases. Margins were assessed in the majority of cases by inking of the resection margins and were classified as positive in 13 cases, close (< or = 2 mm) in 21, negative (>2 mm tumor-free margin) in 417, and indeterminate in 77. Peritumoral vascular invasion was observed in 40 patients. Tamoxifen was administered for at least 2 years in 176 patients. At least six cycles of adjuvant systemic chemotherapy were administered in 116 patients. The mean follow-up period from the beginning of the treatment was 84.5+/-1.7 months. RESULTS: First events included 44 isolated local recurrences, 8 isolated axillary node recurrences, 44 isolated distant metastases, 1 local recurrence with synchronous axillary node recurrence, 7 local recurrences with synchronous metastases, and 2 local recurrences with synchronous axillary node recurrences and distant metastases. Of 39 pathologically evaluable local recurrences, 33 were classified as true local recurrences and 6 as ipsilateral new primary carcinomas. Seventy patients died (47 of breast carcinoma, 4 of other neoplastic diseases, 10 of other diseases and 9 of unknown causes). The 5- and 10-year rates were, respectively: specific survival 93% and 86%, disease-free survival 85% and 75%, distant metastasis 8.5% and 14%, and local recurrence 7% and 14%. Mean intervals from the beginning of treatment for local recurrence or distant metastases were, respectively, 60+/-6 months (median: 47 months, range: 6-217 months) and 49.5+/-5.4 months (median: 33 months, range: 6-217 months). After local recurrence, salvage mastectomy was performed in 46 patients (85%) and systemic hormonal therapy and/or chemotherapy was administered to 43 patients. The 5-year specific survival rate after treatment for local recurrence was 78+/-8.2%. Multivariate analysis (multivariate generalization of the proportional hazards model) showed that the probability of local control was decreased by the following four independent factors: young age (< or = 40 yr vs. >40 yr; relative risk [RR]: 3.15, 95% confidence interval [CI]: 1.7-5.8, p = 0.0002), premenopausal status (pre vs. post; RR: 2.9, 95% CI: 1.4-6, p = 0.0048), bifocality (uni- vs. bifocal; RR: 2.7, 95% CI: 2.6-2.8,p = 0.018), and extensive intraductal component (IC <25% vs. IC > or = 25%; RR: 2.6, 95% CI: 13-5.2, p = 0

Prognosis and treatment of acute lymphoblastic leukemia. Study of 650 patients.

The complete hematological remission (CHR) rate, duration of remission and survival were studied in relation to age, peripheral blast cell (PBC) count, presence or absence of tumor masses, cytological type, and treatment in 650 patients with acute lymphoblastic leukemia. Prognostic factors were considered separately and divided into prognostic classes. Age and PCB count correlated with both the rate and the duration of CHR. This correlation was still observed for more recent treatment schedules though it appears to be becoming progressively less significant. Meningeal relapses were more common in patients less than 1 year old and in those with a high PCB count. It is suggested that stratification of patients according to such factors as age, PCB count, presence or absence of tumor, and cytological type might be necessary for the design of new treatment protocols and for the evaluation of their results.

Comparison of bone scanning and CA 15-3 serum concentration in the follow-up of breast cancer.

The follow-up bone scans (BS) of 158 women with breast cancer and without known bone metastases were reviewed and compared with serum CA 15-3 concentration. Ninety-three BS were systematic (normal serum CA 15-3) and 3 corresponded to proven bone metastases. Sixty-five BS were motivated:-by isolated bone pain (20 BS. 1 corresponding to metastases),-by bone pain and signs of progression of the disease (11 BS. 7 corresponding to metastases: elevated serum CA 15-3 except in one case), by known visceral metastases (20 BS. 6 corresponding to metastases with elevated serum CA 15-3), by an isolated increase of serum CA 15-3 (7 BS. 4 corresponding to metastasis) by local recurrence (7 BS. 1 corresponding to metastasis). These results show that bone metastases were diagnosed in 6 patients whose serum CA 15-3 concentration was normal. We conclude that the existence of normal tumor markers is not sufficient to exclude the possibility of bone metastases.

CA 15-3 and bone scintigraphy in the follow-up of breast cancer.

By means of the retrospective study of the clinical records of 158 women followed for breast cancer, we aimed to evaluate the consequences of a non-systematic indication for bone scan (BS) based either on CA 15-3 levels alone or a combination of tumor marker levels and clinical criteria. With the first option, the negative predictive value was 95% and 82% of the BS would have been avoided. With the second option, the negative predictive value was 97% and 59% of the BS would have been avoided. Furthermore, the preliminary results of a longitudinal study showed that those patients with normal CA 15-3 levels and positive bone scans showed a subsequent rise in CA 15-3 levels which frequently became elevated with a average delay of 15 months. Omission of systematic bone scans in the follow-up of breast cancer patients is likely to lead to a delay in the diagnosis of bone metastasis in 3% to 5%, the consequences of which have to be examined carefully.

[Microangiopathic hemolytic anemia associated with uterine sarcoma: report of a case. Review of the literature]. / Anémie hémolytique microangiopathique associée a un sarcome utérin: rapport d'un cas. Revue de la littérature.

Microangiopathic hemolytic anemia (MAHA) is a rare but severe complication of neoplastic disease. The diagnosis of thrombotic microangiopathy is based on a triad of a hemolytic anemia with schistocytes, thrombocytopenia, and renal failure. Carcinoma-associated MAHA and chemotherapeutic-induced MAHA have been described. Because of differences concerning prognosis and treatment it is important for the clinician to distinguish these two syndromes. However, to our knowledge, this is the first case of a sarcoma-associated thrombotic microangiopathy.

[Desmoid tumors of the mesentery in Gardner's syndrome. Value of x-ray computed tomography]. / Les tumeurs desmoïdes du mésentère dans le cadre du syndrome de Gardner. Intérêt du scanner.

3 cases of desmoid tumours of the mesentery occurring as part of Gardner's syndrome are reported. In 2 cases, CAT scanning was carried out. We underline the value of this examination compared to other imaging methods. It allows the establishment of a diagnosis, investigation for complications, the operability to be assessed and is useful for monitoring patients. Its major value is in avoiding an unnecessary laparotomy, a factor certain to produce recurrence, in certain patients. Other alternative therapy may then be proposed.

[Inflammatory cancer of the breast. Assessment after 6 years of 16 patients treated by primary immunochemotherapy]. / Cancer inflammatoire du sein. Bilan à six ans de 16 malades traitées par immunochimiothérapie première.

Sixteen patients with clinical primary inflammatory carcinoma of the breast were treated with initial immunochemotherapy from September 1974 to May 1977. This chemotherapy was an association of adriamycin, vincristine, fluorouracil, methotrexate, and melphalan. Thermographic cooling was taken as the criterion of operability. Chemotherapy was resumed after surgery up to a total of ten periods, and followed by a minimum one year chemotherapy. I-BCG-F Pasteur was used as immunotherapy and associated with the chemotherapy regimen. Five patients have died, four are alive with disease, and seven are free of disease at time of reporting. Median survival exceeds 90 months. Our data supports the conclusion that mastectomy combined with preoperative and postoperative immunochemotherapy may permit a better prognosis for inflammatory carcinoma of the breast: this benefit seems to be the consequence of adapting the length of initial chemotherapy to the data given by plate-thermography.

[Prognosis of cancer of the breast in women under 40-years-old. Apropos of 55 cases]. / Pronostic du cancer du sein chez la femme de moins de 40 ans. A propos de 55 cas.

Between the years 1972 and 1978, 55 women who were less than 40 years of age at the time of the diagnosis of the condition and of the original treatment were studied. 32 of these had local and regional treatment, which was surgery with or without radiotherapy. The remaining 23 had chemotherapy as well. Their prognosis was compared with those of 288 women who were more than 40 years of age and treated during the same period of time. Various comparisons were carried out between the two groups according to their treatment, the size of the tumour and the degree of lymph node invasion. This showed, on the one hand, that chemotherapy was beneficial in all groups whether they were less or more than 40 years of age, and on the other hand, that being young when the condition was first diagnosed made the prognosis poorer.

[Adenocarcinoma of the pancreas. General characteristics]. / Adénocarcinome du pancréas. Caractères généraux.

EPIDEMIOLOGY: Pancreatic carcinoma ranks fifth among the leading causes of cancer death in developed countries. Although the incidence of pancreatic cancer is about 10 per 100,000 inhabitants, the five-year overall survival is barely one to 4%. Few risk factors have been identified. Smoking increases the relative risk by 1.5, chronic pancreatitis by 26. Hereditary formes are rare. PATHOLOGY AND MOLECULAR ABNORMALITIES: Adenocarcinomas of the ductal phenotype represents about 90% of the pancreatic tumors. Seventy percent of adenocarcinomas are located in the head. Mutations of K-ras oncogene and p53 anti-oncogene are noted, respectively, in 80 to 90% and 70% of the ductal adenocarcinomas. The mutation of p53 is associated with a poor prognosis. Certain less frequent forms such as mucinous cystadenocarcinomas, or intraductal papillary-mucinous tumors seem to have a better prognosis. However, this is not true for acinar cell carcinomas responsible for various paraneoplastic syndromes. PATTERN OF SPREAD: The disease arises in the ductal epithelium and rapidly spreads to regional lymph nodes and the liver. At diagnosis, nodal involvement is found in 80% of cases. Half of the patients have detectable visceral metastasis with a median survival of three to six months. Among the remaining non metastatic patients, approximately one in 5 has undetected peritonal carcinomatosis. Only 10 to 20% of the patients undergo surgical complete resection with a median survival of 15 to 19 months.

[Primary pseudo-ovarian peritoneal carcinosis. 4 cases]. / Carcinoses péritonéales primitives pseudo-ovariennes. Quatre observations.

Primary papillary carcinosis of the peritoneum is a rare disease seen in elderly women in whom no digestive or ovarian carcinoma could be detected. Its histological structure is identical with that of papillary carcinoma of the ovary. The 4 cases reported here were treated as advanced ovarian carcinomas, with multiple chemotherapy including doxorubicin and cis-platinum. Three patients were re-operated upon after 6 courses. Complete remission was obtained in all 4 cases, but the patients relapsed under maintenance therapy. The diagnosis must be suspected in elderly women presenting with unexplained carcinosis. This is particularly important since effective treatments can now be proposed, as for advanced ovarian carcinomas.

[Adenocarcinoma of the pancreas. Diagnosis and evaluation]. / Adénocarcinome du pancréas. Diagnostic et bilan.

SYMPTOMS: Pain, jaundice, or weight loss are the presenting features of 90% of the cases. Patients with tumors of the body or the tail of the pancreas do not rapidly develop jaundice. Therefore, their diagnosis is delayed and metastasis are more frequently detected at diagnosis. RADIOLOGIC DIAGNOSIS: The diagnosis may be established by ultrasonography, endoscopic ultrasonography and most importantly by CT scan with helicoidal continuous acquisition and contrast injection. However, these methods do not efficiently detect tumors smaller than 2 cm or with only superficial peritoneal involvement. Laparoscopy and angiography are used less and less frequently to evaluate resectability. The diagnostic work-up with CT scanning is able to anticipate resectability in 50 to 90% of the cases. PATHOLOGY: Histopathology must be obtained since 10% of the pancreatic carcinoma are not of the ductal type and not all pancreatic tumors are malignant. When a pathological specimen cannot be obtained during surgery, a cytology specimen may be obtained with a fine needle guided by CT scan. PROGNOSIS: Survival depends on the possibility of a complete resection of the tumor. If complete resection is obtained, the prognostic factors are in decreasing importance: tumor size, lymphatic and vascular involvement, and invasion of peri-pancreatic tissues.

[Adenocarcinoma of the pancreas. Therapeutic strategies]. / Adénocarcinome du pancréas. Stratégies thérapeutiques.

SURGERY: Surgery whether curative or palliative, is the major modality of treatment. A complete resection is possible in about 20% of patients with a median survival of 12 to 16 months and a 20% five year survival. After complete resection 70 to 80% of patients develop a local recurrence. Biliary and gastro-intestinal bypasses as well as antalgic techniques are useful palliative procedures. ADJUVANT AND NEOADJUVANT TREATMENT: Chemoradiotherapy is used either as adjuvant or neoadjuvant treatment. External beam irradiation techniques are used to deliver 45 to 50 Gy to the pancreas in five to six weeks. Concomitant fluorouracil is administered in bolus injections or better in continuous infusion,, either alone or in association with cisplatinum. Chemoradiotherapy reduces the local relapse rate and slightly, though significantly, increases the median survival. Therefore, after chemoradiotherapy, metastatic spread becomes the major cause of death. PALLIATIVE TREATMENT: For locally advanced diseases, chemoradiotherapy has a true palliative effect with acceptable toxicity. Metastatic disease remains a challenge. Fluorouracil based chemotherapy with or without cisplatinum occasionally obtains effective palliation. Among new agents, only gemcitabine has proven clinical activity associated with low toxicity and is practical to use. THERAPEUTIC STRATEGY: Presently, patients with resectable pancreatic carcinoma should be included in a prospective trial to receive combined modality treatment with adjuvant or neo-adjuvant chemoradiotherapy. The choice of treatment for patients with locally advanced or metastatic disease, should be based on the possibility of assuring a satisfactory quality of life. Present research should progress through controlled clinical trials to study original systemic treatment and combined modalities able to produce a lasting local control.

[Therapeutic intensification and autotransplantation of hematopoietic stem cells in metastatic breast cancers]. / Intensification thérapeutique et autogreffe de cellules souches hématopoïétiques dans les cancers du sein métastatiques.

The first studies on intensive chemotherapy for metastatic breast cancer conducted in the 80s were disappointing. Despite good response rates, the duration of remission was short and long-term survivals exceptional. Nevertheless, these phase I and II trials helped to develop a better understanding of the potential indications of this new therapeutic approach and apprehend its technical aspects. Over the last 5 years, considerable progress has been made in grafting techniques and hematopoietic support greatly improving the safety of the method. Notwithstanding the financial considerations involved, it must be noted that the efficacy autologous stem cell support, in terms of recurrence-free overall survival, has not yet been demonstrated although the (controversial) results of two randomized controlled trials have recently been published. In France, the PEGASE programs for the study of autologous stem cell support in breast cancer have been developed in an attempt to elucidate the question.

[Splenectomy for hematologic indications. Indications, early results (author's transl)]. / Les splénectomies "d'indication hématologique" Indications. Résultats précoces.

In the light of their personal experience of 1,036 splenectomies, the authors review the hematological diseases which still require surgery, viz. certain hemolytic anemias, idiopathic thrombocytopenic purpura, Hodgkin's disease under certain conditions, and sometimes the splenic lesions in certain malignant blood diseases; they analyse their results. Thanks to close collaboration between hematologists and intensive care specialists, the mortality has been reduced to 1.35 p. cent and the morbidity to 3.46 p. cent which leaves 95.19 p. cent without any immediate postoperative complications. The late results depend on the initial disease process.