Georgoulias V; Androulakis N; Bouros D; Kouroussis C; Chatzakis K; Papadakis M; Apostopoloulou F; Georgopoulou T; Kotsakis T; Souklakos J; Hatzidaki D; Vlachonikolis J; Panagos G.  Combination chemotherapy with docetaxel, vinorelbine and cisplatin as first-line treatment of advanced non-small-cell lung cancer: a multicenter phase II study of the Greek Cooperative Group for Lung Cancer. Department of Medical Oncology, University General Hospital of Heraklion, Crete, Greece. Lung Cancer, 21(3):213-20 1998 Sep

Vinorelbine, docetaxel and cisplatin have documented single-agent activity in non-small-cell lung cancer (NSCLC); a multicenter phase II trial was initiated in order to evaluate the tolerance and efficacy of their combination. A total of 24 chemotherapy-naive patients with measurable stage IIIB or IV NSCLC and performance status (PS; WHO) 0-2 entered the study. Vinorelbine (20 mg/m2 i.v.) was given on days 1 and 15, cisplatin (60 mg/m2) on day 1, and docetaxel (100 mg/m2) on day 16, in cycles of 28 days. Recombinant human granulocyte colony-stimulating factor (150 microg/m2 s.c.) was administered prophylactically from day 17 to day 27. One pathological complete (4%) and six partial responses (25%) were documented (overall response 29%; 95% CI 11.6-49.2%). A total of five patients (21%) had stable and 12 (50%) progressive disease. The median duration of response was 28 weeks and the median time to tumor progression 36 weeks; the median survival was 20 weeks. Grade 3-4 neutropenia occurred in 16 patients (67%) while 13 of them (54%) developed febrile neutropenia. Grade 4 mucositis occurred in two patients (8%) and one of them also presented grade 4 diarrhea. There were four treatment-related deaths: two from sepsis, one from massive hemoptysis due to a pulmonary abscess and one from acute myocardial ischemia 7 days post-chemotherapy. In conclusion, the high incidence of neutropenic episodes and treatment-related deaths led to an early discontinuation of patient enrollment. This combination, in the schedule and the doses used, could not be recommended for off protocol treatment of patients with advanced NSCLC.

Paul Dennis: 36 total patients. All patients died of cancer, except 4 patients (11%) who died of the cocktail's toxicity. 7 had temporary remissions and lived 7 months longer than the rest.

Twelves CJ; Dobbs NA; Curnow A; Coleman RE; Stewart AL; Tyrrell CJ; Canney P; Rubens RD. A phase II, multicentre, UK study of vinorelbine in advanced breast cancer. Imperial Cancer Research Fund Clinical Oncology Unit, UMDS, Guy's Hospital, London, UK. Br J Cancer, 70(5):990-3 1994 Nov

Thirty-four evaluable patients were treated with vinorelbine, a novel, semisynthetic vinca alkaloid, as first-line chemotherapy for advanced breast cancer. They received vinorelbine 25 mg m-2 i.v. given weekly for a maximum of 16 cycles. Two patients achieved a complete remission and 15 a partial remission, giving a response rate of 17/34 (50%; 95% CI of 34-66%); median response duration was 5.8 months. The median progression-free interval was 4.4 months and median survival 9.9 months. Treatment was generally well tolerated. Fatigue was the most common side-effect. The main reason for dose adjustments was myelosuppression; 68% of patients had WHO grade 3 or 4 neutropenia and there was one death attributed to neutropenic sepsis. Nausea/vomiting and neuropathy were mild and alopecia was uncommon. This study confirms vinorelbine as a highly active, well-tolerated agent in advanced breast cancer worthy of evaluation in combination chemotherapy regimens.

Paul Dennis: 34 total patients. All patients died of cancer, except for 1 patient who died of vinorelbine toxicity. 17 had temporary remissions and lived 6 months longer than the rest.

Cerny T; Kaplan S; Pavlidis N; Sch¨offski P; Epelbaum R; van Meerbeek J; Wanders J; Franklin HR; Kaye S. Docetaxel (Taxotere) is active in non-small-cell lung cancer: a phase II trial of the EORTC Early Clinical Trials Group (ECTG) [see comments] Institut f¨ur Medizinische Onkologie, Berne, Switzerland. Br J Cancer, 70(2):384-7 1994 Aug

In a multicentre trial of the EORTC ECTG we have treated 43 non-pretreated patients with advanced non-small-cell lung cancer (NSCLC) with the new semisynthetic taxoid docetaxel (Taxotere). Six patients were ineligible; of the 37 eligible patients, ten had prior radiotherapy and 18 prior surgery. They received 100 mg m-2 in 1 h i.v. every 3 weeks, usually in an outpatient setting. Prophylactic steroids, antihistaminics or antiemetics were not routinely given. Two patients were not evaluable because they withdrew from the study because of a hypersensitivity reaction after the second cycle. The main toxicity was neutropenia (80% of cycles), although infections were rare (4%). One patient died from sepsis during neutropenia. Hypersensitivity reactions necessitating interruption of docetaxel (Taxotere) infusions were found in only 10% of cycles. The overall response rate was 23% with one complete response, and seven partial responses. Stable disease was found in 16 patients. The median duration of response was 36 weeks, and the median survival of all patients was 11 months. Docetaxel (Taxotere) is among the most active drugs for treatment of NSCLC.

Paul Dennis: 37 total patients. All patients died of cancer, except for 1 patient who died of docetaxel toxicity. 8 had temporary remissions and lived 9 months longer than the rest

De Jager R; Longeval E; Klastersky J.   High-dose cisplatin with fluid and mannitol-induced diuresis in advanced lung cancer: a phase II clinical trial of the EORTC Lung Cancer Working Party (Belgium). Cancer Treat Rep, 64(12):1341-6 1980

A phase II clinical trial of high-dose cisplatin (120 mg/m2 iv every 3 weeks), with fluid and mannitol-induced diuresis, was conducted in 81 patients with advanced lung cancer. Partial remissions were documented in 26% of 75 evaluable cases for a median duration of 3.5 months. Adenocarcinoma and small cell anaplastic carcinoma were more responsive than epidermoid carcinoma, with partial response rates of 35%, 30%, and 18%, respectively. The median survival of responders (8.5 months) was significantly longer than the survival of nonresponders (4 months) (P less than 0.02). Myelosuppression was mild. Renal toxicity with peak serum creatinine greater than 2.5 mg/100 ml occurred in eight patients, with one death occurring due to toxicity. Cisplatin is an active drug in advanced lung cancer. 1980

Paul Dennis: 80 total patients.All patients died of cancer, except for 1 patient who died of cisplatin toxicity. 17 had temporary remissions and lived 4.5 months longer than the rest.

Leukemia

Riley LC, et al Treatment-related deaths during induction and first remission of acute myeloid leukaemia in children treated on the Tenth Medical Research Council Acute Myeloid Leukaemia Trial (MRC AML10). Br J Haematol. 1999 Aug;106(2):436-444. [Record as supplied by publisher] PMID: 10460604.

Between 1988 and 1995, 341 children with acute myeloid leukaemia (AML) were treated on the Medical Research Council Acute Myeloid Leukaemia Trial (MRC AML10). The 5-year overall survival was 57%, much improved on previous trials. However, there were 47 deaths (13.8%), 11 of which were associated with bone marrow transplantation (BMT). The treatment-related mortality was significant at 13.8%, but decreased in the latter half of the trial from 17.8% in 1998-91 to 9.6% in 1992-95 (P = 0.03%). The main causes of death were infection (65.9%), haemorrhage (19.1%) and cardiac failure (19.1%). Fungal infection was a significant problem, causing 23% of all infective deaths. Haemorrhage occurred early in treatment, in children with initial white cell counts >100 x 109/l (P = 0.001), and was more common in those with M4 and M5 morphology. Cardiac failure only occurred from the third course of chemotherapy onwards, with 78% (7/9) in conjunction with sepsis as a terminal event. Some deaths could be prevented by identifying those most at risk, and with prompt recognition and aggressive management of complications of treatment. Future options include the prophylactic use of antifungal agents, and the use of cardioprotectants or alternatives to conventional anthracyclines to decrease cardiac toxicity. PMID: 10460604

DiMario FJ Jr !990), Packer RJ Pediatrics 1990 Mar 85:3 353-60. Acute mental status changes in children with systemic cancer.

Acute changes in mental status (AMS) develop in children with cancer from a multitude of cancer- and treatment-related complications. To determine the incidence, etiology, and outcome of children with cancer who had AMS, the medical records of all children under 18 years of age with systemic cancer (excluding primary central nervous system tumors) who had AMS in our institution during the years 1981 through 1987 were reviewed. AMS developed in 89 of 815 children at risk (11%). The AMS was caused by seizures in 53 (60%), an encephalopathy in 24 (27%), and a stroke syndrome in 12 (13%). AMS occurred in 42 of 305 (14%) with leukemia, 16 of 139 (12%) with lymphoma, 14 of 136 (10%) with sarcoma, 10 of 104 (9%) with neuroblastoma, and 7 of 104 (5%) with other malignancies. Children with acute lymphocytic leukemia were more prone to having seizures (61%), while children with nonacute lymphocytic leukemia were almost equally likely to have encephalopathies, strokes, or seizures. Children with lymphoma were admitted for treatment most often with an encephalopathy (44%). Etiologies for AMS were evaluated vigorously, and one or more etiologies were identified in 80 of 89 (89%) patients. Dependent on the type of tumor, the anticancer treatment used and, timing during the course of illness AMS occurred, specific diagnoses were more likely. Neurologic morbidity and mortality were dependent on the cause of AMS. Children with seizures that were initially difficult to control were more likely to require long-term anticonvulsant therapy.

"Results of treatment with cyclophosphamide, doxorubicin,
vincristine and prednisone (CHOP) for non-Hodgkin's aggressive
lymphoma analyzed according to the International Prognostic Index."
>The overall survival rate (2 yr) of 23 patients in the L+LI risk
>group was 52.1% and of 17 patients in H+HI risk group was
>11.7% and this difference was statistically significant (P<0.05).
>Our results indicated that the CHOP regimen is not effective
>in the HI+H risk groups of patients with aggressive NHL.

This says CHOP only achieved a 52.1% survival rate after two
years in the low and low-intermediate risk groups. It also says
that 11.7% survival in the high and high-intermediate risk group
was not an improvement over untreated aggressive NHL.

Since the H+HI group has three times the risk factor of the
L+LI group, 35% (3*11.7%) or more of the L+LI group were
expected to survive 2 years without any treatment at all.
At best, the CHOP study shows only a 17% improvement in
the survival rate at 2 years.

How can you claim that CHOP "has a CURE rate of over 50%"
complete remission for 5 years, when 48% of the low+low-intermediate
group are already dead at 2 years, and when 68% of all groups
combined are dead at 2 years? Get serious.

NHL is extremely rare, and is one of only four types of cancer
where chemotherapy sometimes beats the odds. Barely. All
4 are extremely rare: testicular, choriocarcinoma, childhood
leukemia, and hodgkins.